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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00546416




Registration number
NCT00546416
Ethics application status
Date submitted
11/09/2000
Date registered
27/01/2003
Date last updated
25/03/2015

Titles & IDs
Public title
S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma
Scientific title
Phase III Trial of High Dose Interferon Alfa 2-b Versus Cisplatin, Vinblastine, DTIC Plus IL-2 and Interferon in Patients With High Risk Melanoma
Secondary ID [1] 0 0
U10CA032102
Secondary ID [2] 0 0
S0008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma (Skin) 0 0
Unspecified Adult Solid Tumor, Protocol Specific 0 0
Unspecified Childhood Solid Tumor, Protocol Specific 0 0
Paget's Disease of Bone 0 0
Leukemia 0 0
Cutaneous T Cell Lymphoma 0 0
Peripheral T Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Breast
Neurological 0 0 0 0
Other neurological disorders
Injuries and Accidents 0 0 0 0
Poisoning
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - interleukin-2
Treatment: Other - filgrastim
Treatment: Other - interferon alfa
Treatment: Drugs - cisplatin
Treatment: Drugs - dacarbazine
Treatment: Drugs - vinblastine
Treatment: Drugs - Zoledronic Acid
Treatment: Drugs - Risedronate
Treatment: Drugs - Placebo to Risedronate
Treatment: Drugs - Placebo to Zoledronic Acid
Treatment: Other - Calcium and Vitamin D

Experimental: AC followed by Docetaxel + Herceptin (AC?TH) - Doxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose.

Active comparator: Arm I - Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II - Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Docetaxel + Carboplatin + Herceptin (TCH) - Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 1 only, followed by Herceptin 2 mg/kg IV infusion weekly starting from Day 8 until three weeks after the last cycle of chemotherapy. Docetaxel 75 mg/ m² IV infusion on Day 2 of Cycle 1, then on Day 1 of all subsequent cycles followed by carboplatin IV infusion at target AUC = 6 mg/mL/min repeated every 3 weeks for a total of 6 cycles. After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg by IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose.

Experimental: Zoledronic Acid and Placebo to Risedronate - Participants received zoledronic acid 5 mg intravenous infusion one dose, 60 days of oral placebo to risedronate, calcium 500 mg twice a day and vitamin D 400 to 1000 international units daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Active comparator: Risedronate and Placebo to Zoledronic Acid - Participants received 60 days of oral risedronate 30 mg, one intravenous infusion of placebo to zoledronic acid, calcium 500 mg twice a day and vitamin D 400 to 1000 international units daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Experimental: Peripheral T-cell Lymphoma (PTCL) - Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m\^2 and at 17.5 mg/m\^2 on days 1, 8, and 15 of a 28 day cycle.

Experimental: Cutaneous T-cell Lymphoma (CTCL) - Participants received at least one protocol prescribed dose or higher of Romidepsin intravenously at 14mg/m\^2 and at 17.5 mg/m\^2 on days 1, 8, and 15 of a 28 day cycle.


Treatment: Other: interleukin-2
Given IV

Treatment: Other: filgrastim
Given subcutaneously

Treatment: Other: interferon alfa
Given IV and subcutaneously

Treatment: Drugs: cisplatin
Given IV

Treatment: Drugs: dacarbazine
Given IV

Treatment: Drugs: vinblastine
Given IV

Treatment: Drugs: Zoledronic Acid
Zoledronic acid 5 mg in 5 mL of sterile water intravenous infusion.

Treatment: Drugs: Risedronate
Oral risedronate 30 mg capsules.

Treatment: Drugs: Placebo to Risedronate
Oral placebo of risedronate capsules.

Treatment: Drugs: Placebo to Zoledronic Acid
5 mL of sterile water one dose intravenous infusion.

Treatment: Other: Calcium and Vitamin D
Calcium and vitamin D supplements were supplied.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
5-year Overall Survival
Timepoint [1] 0 0
Every three months for a year, every six months for years 2-5, annual for years 5-10
Primary outcome [2] 0 0
5-year Relapse-Free Survival
Timepoint [2] 0 0
Every three months for the first year, every 6 months for years 2-5, annually for years 6-10
Primary outcome [3] 0 0
Percentage of Participants With Disease Free Survival at 5 Years
Timepoint [3] 0 0
From randomization until relapse or death or up to 5 years
Primary outcome [4] 0 0
Number of Patients Who Achieve Therapeutic Response at 6 Months.
Timepoint [4] 0 0
6 months
Primary outcome [5] 0 0
Number of Participants With a Response
Timepoint [5] 0 0
up to 56.5 days
Primary outcome [6] 0 0
Duration of Response (DOR)
Timepoint [6] 0 0
up to 127 months
Secondary outcome [1] 0 0
Toxicity
Timepoint [1] 0 0
While on treatment, patients on the HDIFN arm were assessed weekly for the 1st month, then every 2 weeks for the 2nd month, then every 3 months therafter; patients on the biochemo arm were assessed daily for the 1st 5 days, then weekly thereafter.
Secondary outcome [2] 0 0
Percentage of Participants With Disease Free Survival at 10 Years
Timepoint [2] 0 0
From randomization until relapse or death or up to 10 years
Secondary outcome [3] 0 0
Overall Survival- Percentage of Participants Who Survived at 10 Years
Timepoint [3] 0 0
From randomization until death or up to 10 years
Secondary outcome [4] 0 0
Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28
Timepoint [4] 0 0
Baseline and day 28
Secondary outcome [5] 0 0
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10
Timepoint [5] 0 0
Baseline and day 10
Secondary outcome [6] 0 0
Relative Change in Urine Alpha C-telopeptide (a-CTx) in ug/mmol at Day 10
Timepoint [6] 0 0
Baseline and day 10
Secondary outcome [7] 0 0
Time to First Therapeutic Response
Timepoint [7] 0 0
182 days
Secondary outcome [8] 0 0
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline
Timepoint [8] 0 0
Baseline and day 28
Secondary outcome [9] 0 0
Change in Pain Severity Score
Timepoint [9] 0 0
Baseline and day 182
Secondary outcome [10] 0 0
Change in Pain Interference Score
Timepoint [10] 0 0
Baseline and day 182
Secondary outcome [11] 0 0
Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period
Timepoint [11] 0 0
8 years was the maximum
Secondary outcome [12] 0 0
Number of Participants With a Partial Disease Relapse During the Extended Observation Period
Timepoint [12] 0 0
8 years was the maximum
Secondary outcome [13] 0 0
Number of Participants With a Disease Relapse During the Extended Observation Period
Timepoint [13] 0 0
8 years was the maximum
Secondary outcome [14] 0 0
Number of Participants With Adverse Events
Timepoint [14] 0 0
147 months and 5 days
Secondary outcome [15] 0 0
Median Number of Cycles of Depsipeptide Administered
Timepoint [15] 0 0
83 cycles (i.e., each cycle is 21 days)
Secondary outcome [16] 0 0
Time to Progression
Timepoint [16] 0 0
Until disease progression, or 30 days following off study date
Secondary outcome [17] 0 0
Fold Change in Histone Acetylation
Timepoint [17] 0 0
4 hours, 24 hours, and 48 hours after Romidepsin
Secondary outcome [18] 0 0
Multidrug Resistance Protein 1 (MDR1) or ATP-binding Cassette Sub-family B Member 1 (ABCB1) Gene Expression
Timepoint [18] 0 0
4 hours, 24 hours, and 48 hours after Romidepsin

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

* Histologically proven melanoma of cutaneous origin or from unknown primary at initial presentation of primary or first clinically detected nodal or satellite/in-transit recurrence

* No distant metastases
* No melanoma of ocular, mucosal, or other non-cutaneous origin
* One of the following criteria must apply for patients with newly diagnosed melanoma OR a previously diagnosed primary with current subsequent, clinical, regional nodal disease and/or satellite/in-transit disease:

* Ulcerated primary melanoma with 1 or more involved lymph nodes (micro/occult or macro/clinically overt)
* Non-ulcerated or unknown primary melanoma with one macro/clinically overt lymph node metastasis, including a single matted nodal mass

* No non-ulcerated or unknown primary tumor and a single micrometastatic lymph node
* Non-ulcerated melanoma with two or more lymph node metastases (micro/occult or macro/clinically overt) and/or matted nodes
* Any satellite/in transit metastasis with or without lymph node involvement
* Patients with recurrent disease must have recurrent disease in the regional nodal basin of a prior complete lymphadenectomy
* Multiple regional nodal basin involvement allowed if they are appropriate anatomic drainage basins for primary site
* Patients must be disease free at time of enrollment based on the following surgical criteria:

* Patients at initial presentation of melanoma must undergo adequate wide excision of primary lesion
* Patients with previously diagnosed melanoma must have all disease resected with pathologically negative margins and no disease at primary site or second resection of primary
* Full lymphadenectomy required of all patients including those with positive sentinel nodes or positive satellite/in-transit metastasis
* No more than 56 days since prior lymphadenectomy OR surgery to remove recurrent disease after prior complete lymphadenectomy
* Must be willing to participate in minimal residual disease studies if registered on the study on 3/1/2003 or later

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Absolute granulocyte count at least 1,500/mm^3
* Platelet count at least 100,000/mm^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* SGOT or SGPT no greater than 2 times ULN
* LDH and alkaline phosphatase no greater than 2 times ULN (above normal value requires a contrast-enhanced CT scan or MRI of liver)
* No known recent hepatitis positivity by PCR

Renal:

* Creatinine no greater than 1.5 mg/dL OR
* Creatinine clearance at least 75 mL/min

Cardiovascular:

* No congestive heart failure
* No coronary artery disease
* No serious cardiac arrhythmia
* No prior myocardial infarction
* Normal cardiac stress test required if any of the following are present:

* Over age 50
* Abnormal EKG
* History of cardiac disease

Pulmonary:

* No symptomatic pulmonary disease

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No autoimmune disorders or conditions of immunosuppression
* No other prior malignancy within the past 5 years except the following:

* Adequately treated basal cell or squamous cell skin cancer
* Carcinoma in situ of the cervix
* Adequately treated stage I or II cancer in remission
* HIV negative
* No known AIDS or HIV-1 associated complex

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior immunotherapy, including interferon, interleukin, levamisole, or other biologic response modifiers
* No other concurrent biologic therapy

Chemotherapy:

* No prior chemotherapy (including infusion or perfusion therapy)
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent systemic corticosteroids or topical steroid creams
* Concurrent steroid antihistamines allowed if no alternative
* No concurrent hormonal therapy

Radiotherapy:

* No prior radiotherapy

* Prior postlumpectomy radiotherapy for breast cancer allowed
* No concurrent radiotherapy

Surgery:

* See Disease Characteristics
* No concurrent surgery

Other:

* No concurrent anti-hypertensive medications (arm II only)
* No concurrent immunosuppressive agents
* No other concurrent anticancer therapy
* Antihistamines allowed if no alternative medication suitable
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2000
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2012
Sample size
Target
Accrual to date
Final
432
Recruitment in Australia
Recruitment state(s)
WA,NSW,VIC
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [2] 0 0
Sanofi-Aventis Administrative Office - Macquarie Park
Recruitment hospital [3] 0 0
Westmead Institute for Cancer Research at Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Novartis Investigative Site - Concord
Recruitment hospital [5] 0 0
Novartis Investigative Site - Fitzroy
Recruitment hospital [6] 0 0
Novartis Investigative site - Geelong
Recruitment hospital [7] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [8] 0 0
Novartis Investigative site - Maroochydore
Recruitment hospital [9] 0 0
Novartis Investigative site - Nedlands
Recruitment hospital [10] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [11] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [12] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [13] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment postcode(s) [1] 0 0
6001 - Perth
Recruitment postcode(s) [2] 0 0
- Macquarie Park
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
- Concord
Recruitment postcode(s) [5] 0 0
- Fitzroy
Recruitment postcode(s) [6] 0 0
- Geelong
Recruitment postcode(s) [7] 0 0
- Kogarah
Recruitment postcode(s) [8] 0 0
- Maroochydore
Recruitment postcode(s) [9] 0 0
- Nedlands
Recruitment postcode(s) [10] 0 0
3052 - Parkville
Recruitment postcode(s) [11] 0 0
- Adelaide
Recruitment postcode(s) [12] 0 0
- Melbourne
Recruitment postcode(s) [13] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
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Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
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District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Idaho
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United States of America
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Illinois
Country [13] 0 0
United States of America
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Indiana
Country [14] 0 0
United States of America
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Iowa
Country [15] 0 0
United States of America
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Kansas
Country [16] 0 0
United States of America
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Louisiana
Country [17] 0 0
United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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Montana
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United States of America
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Nebraska
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New Hampshire
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United States of America
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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Wisconsin
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United States of America
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Wyoming
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Argentina
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Buenos Aires
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Austria
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Vienna
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Belgium
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Diegem
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Bosnia and Herzegovina
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Sarajevo
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Brazil
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Sao Paulo
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Bulgaria
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Vazrjdane Region
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Québec
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Colombia
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Bogota
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Croatia
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Zagreb
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Czech Republic
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Praha
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Egypt
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Cairo
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Estonia
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Tallin
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France
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Paris
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Germany
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Frankfurt
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Greece
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Kallithea
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Hong Kong
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Hong Kong
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Hungary
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Budapest
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India
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Mumbai
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Ireland
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Dublin
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Israel
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Natanya
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Italy
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Milan
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Korea, Republic of
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Seoul
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Lebanon
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Beirut
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Mexico
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Col. Coyoacan
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New Zealand
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Macquarie Park
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Poland
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Warsaw
Country [69] 0 0
Romania
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Bucuresti
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Russian Federation
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Moscow
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Slovakia
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Bratislava
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Slovenia
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Ljubljana
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South Africa
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Gauteng
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Spain
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Barcelona
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Sweden
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Bromma
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Switzerland
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Genève
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Taiwan
State/province [77] 0 0
Taipei
Country [78] 0 0
Tunisia
State/province [78] 0 0
Megrine
Country [79] 0 0
Turkey
State/province [79] 0 0
Istanbul
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Guildford Surrey
Country [81] 0 0
Uruguay
State/province [81] 0 0
Montevideo
Country [82] 0 0
Venezuela
State/province [82] 0 0
Caracas
Country [83] 0 0
United States of America
State/province [83] 0 0
Hawaii
Country [84] 0 0
United States of America
State/province [84] 0 0
Kentucky
Country [85] 0 0
United States of America
State/province [85] 0 0
Maine
Country [86] 0 0
United States of America
State/province [86] 0 0
Mississippi
Country [87] 0 0
United States of America
State/province [87] 0 0
Oklahoma
Country [88] 0 0
United States of America
State/province [88] 0 0
Vermont
Country [89] 0 0
Canada
State/province [89] 0 0
Alberta
Country [90] 0 0
Canada
State/province [90] 0 0
British Columbia
Country [91] 0 0
Canada
State/province [91] 0 0
Manitoba
Country [92] 0 0
Canada
State/province [92] 0 0
Ontario
Country [93] 0 0
Canada
State/province [93] 0 0
Quebec
Country [94] 0 0
Canada
State/province [94] 0 0
Saskatchewan
Country [95] 0 0
Switzerland
State/province [95] 0 0
Geneva
Country [96] 0 0
United States of America
State/province [96] 0 0
Rhode Island
Country [97] 0 0
Canada
State/province [97] 0 0
Calgary
Country [98] 0 0
Canada
State/province [98] 0 0
London
Country [99] 0 0
Canada
State/province [99] 0 0
Montreal
Country [100] 0 0
Canada
State/province [100] 0 0
Ste-Foy
Country [101] 0 0
Canada
State/province [101] 0 0
Toronto
Country [102] 0 0
New Zealand
State/province [102] 0 0
Auckland
Country [103] 0 0
New Zealand
State/province [103] 0 0
Christchurch
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Spain
State/province [104] 0 0
Salamanca
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Liverpool
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Manchester
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United Kingdom
State/province [107] 0 0
Nottingham
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Oxford
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Penarth
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Pernarth
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Stanmore
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Vale of Glamorgan

Funding & Sponsors
Primary sponsor type
Other
Name
SWOG Cancer Research Network
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Eastern Cooperative Oncology Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cancer and Leukemia Group B
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Children's Oncology Group
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Cancer International Research Group (CIRG)
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Children's Oncology Group
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Other collaborator category [7] 0 0
Government body
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National Cancer Institute (NCI)
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Other
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Children's Oncology Group
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Ethics approval
Ethics application status

Summary
Brief summary
RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2, in treating patients who have melanoma.
Trial website
https://clinicaltrials.gov/study/NCT00546416
Trial related presentations / publications
Flaherty LE, Othus M, Atkins MB, Tuthill RJ, Thompson JA, Vetto JT, Haluska FG, Pappo AS, Sosman JA, Redman BG, Moon J, Ribas A, Kirkwood JM, Sondak VK. Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. J Clin Oncol. 2014 Nov 20;32(33):3771-8. doi: 10.1200/JCO.2013.53.1590. Epub 2014 Oct 20.
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. doi: 10.1056/NEJMoa0910383.
Au HJ, Eiermann W, Robert NJ, Pienkowski T, Crown J, Martin M, Pawlicki M, Chan A, Mackey J, Glaspy J, Pinter T, Liu MC, Fornander T, Sehdev S, Ferrero JM, Bee V, Santana MJ, Miller DP, Lalla D, Slamon DJ; Translational Research in Oncology BCIRG 006 Trial Investigators. Health-related quality of life with adjuvant docetaxel- and trastuzumab-based regimens in patients with node-positive and high-risk node-negative, HER2-positive early breast cancer: results from the BCIRG 006 Study. Oncologist. 2013;18(7):812-8. doi: 10.1634/theoncologist.2013-0091. Epub 2013 Jun 28.
Perez EA, Press MF, Dueck AC, Jenkins RB, Kim C, Chen B, Villalobos I, Paik S, Buyse M, Wiktor AE, Meyer R, Finnigan M, Zujewski J, Shing M, Stern HM, Lingle WL, Reinholz MM, Slamon DJ. Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat. 2013 Feb;138(1):99-108. doi: 10.1007/s10549-013-2444-y. Epub 2013 Feb 19.
Press MF, Sauter G, Buyse M, Bernstein L, Guzman R, Santiago A, Villalobos IE, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Bee V, Taupin H, Flom KJ, Tabah-Fisch I, Pauletti G, Lindsay MA, Riva A, Slamon DJ. Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol. 2011 Mar 1;29(7):859-67. doi: 10.1200/JCO.2009.27.5644. Epub 2010 Dec 28.
Stern HM, Gardner H, Burzykowski T, Elatre W, O'Brien C, Lackner MR, Pestano GA, Santiago A, Villalobos I, Eiermann W, Pienkowski T, Martin M, Robert N, Crown J, Nuciforo P, Bee V, Mackey J, Slamon DJ, Press MF. PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance. Clin Cancer Res. 2015 May 1;21(9):2065-74. doi: 10.1158/1078-0432.CCR-14-2993. Epub 2015 Feb 3.
Press MF, Sauter G, Buyse M, Fourmanoir H, Quinaux E, Tsao-Wei DD, Eiermann W, Robert N, Pienkowski T, Crown J, Martin M, Valero V, Mackey JR, Bee V, Ma Y, Villalobos I, Campeau A, Mirlacher M, Lindsay MA, Slamon DJ. HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials. J Clin Oncol. 2016 Oct 10;34(29):3518-3528. doi: 10.1200/JCO.2016.66.6693.
Widemann BC, Balis FM, Shalabi A, Boron M, O'Brien M, Cole DE, Jayaprakash N, Ivy P, Castle V, Muraszko K, Moertel CL, Trueworthy R, Hermann RC, Moussa A, Hinton S, Reaman G, Poplack D, Adamson PC. Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2. J Natl Cancer Inst. 2004 Oct 20;96(20):1557-9. doi: 10.1093/jnci/djh270.
Widemann BC, Balis FM, Shalabi A, et al.: Carboxypeptidase-G2 (CPDG2) treatment of accidental intrathecal (IT) methotrexate (MTX) overdose. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-490, 2002.
de Nigris F, Balestrieri ML, Napoli C. Targeting c-Myc, Ras and IGF cascade to treat cancer and vascular disorders. Cell Cycle. 2006 Aug;5(15):1621-8. doi: 10.4161/cc.5.15.3138. Epub 2006 Aug 1.
Widemann BC, Arceci RJ, Jayaprakash N, Fox E, Zannikos P, Goodspeed W, Goodwin A, Wright JJ, Blaney SM, Adamson PC, Balis FM. Phase 1 trial and pharmacokinetic study of the farnesyl transferase inhibitor tipifarnib in children and adolescents with refractory leukemias: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Feb;56(2):226-33. doi: 10.1002/pbc.22775. Epub 2010 Sep 21.
Piekarz RL, Frye AR, Wright JJ, Steinberg SM, Liewehr DJ, Rosing DR, Sachdev V, Fojo T, Bates SE. Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma. Clin Cancer Res. 2006 Jun 15;12(12):3762-73. doi: 10.1158/1078-0432.CCR-05-2095.
Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD. Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215.
Ritchie D, Piekarz RL, Blombery P, Karai LJ, Pittaluga S, Jaffe ES, Raffeld M, Janik JE, Prince HM, Bates SE. Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report. Haematologica. 2009 Nov;94(11):1618-22. doi: 10.3324/haematol.2009.008607. Epub 2009 Jul 16.
Bates SE, Zhan Z, Steadman K, Obrzut T, Luchenko V, Frye R, Robey RW, Turner M, Gardner ER, Figg WD, Steinberg SM, Ling A, Fojo T, To KW, Piekarz RL. Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma. Br J Haematol. 2010 Jan;148(2):256-67. doi: 10.1111/j.1365-2141.2009.07954.x. Epub 2009 Oct 28.
Akilov OE, Grant C, Frye R, Bates S, Piekarz R, Geskin LJ. Low-dose electron beam radiation and romidepsin therapy for symptomatic cutaneous T-cell lymphoma lesions. Br J Dermatol. 2012 Jul;167(1):194-7. doi: 10.1111/j.1365-2133.2012.10905.x.
Noonan AM, Eisch RA, Liewehr DJ, Sissung TM, Venzon DJ, Flagg TP, Haigney MC, Steinberg SM, Figg WD, Piekarz RL, Bates SE. Electrocardiographic studies of romidepsin demonstrate its safety and identify a potential role for K(ATP) channel. Clin Cancer Res. 2013 Jun 1;19(11):3095-104. doi: 10.1158/1078-0432.CCR-13-0109. Epub 2013 Apr 15.
Bates SE, Eisch R, Ling A, Rosing D, Turner M, Pittaluga S, Prince HM, Kirschbaum MH, Allen SL, Zain J, Geskin LJ, Joske D, Popplewell L, Cowen EW, Jaffe ES, Nichols J, Kennedy S, Steinberg SM, Liewehr DJ, Showe LC, Steakley C, Wright J, Fojo T, Litman T, Piekarz RL. Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data. Br J Haematol. 2015 Jul;170(1):96-109. doi: 10.1111/bjh.13400. Epub 2015 Apr 19.
Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, Kirschbaum MH, Zain J, Prince HM, Leonard JP, Geskin LJ, Reeder C, Joske D, Figg WD, Gardner ER, Steinberg SM, Jaffe ES, Stetler-Stevenson M, Lade S, Fojo AT, Bates SE. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5410-7. doi: 10.1200/JCO.2008.21.6150. Epub 2009 Oct 13.
Piekarz RL, Frye R, Prince HM, Kirschbaum MH, Zain J, Allen SL, Jaffe ES, Ling A, Turner M, Peer CJ, Figg WD, Steinberg SM, Smith S, Joske D, Lewis I, Hutchins L, Craig M, Fojo AT, Wright JJ, Bates SE. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011 Jun 2;117(22):5827-34. doi: 10.1182/blood-2010-10-312603. Epub 2011 Feb 25.
Shustov A, Coiffier B, Horwitz S, Sokol L, Pro B, Wolfson J, Balser B, Eisch R, Popplewell L, Prince HM, Allen SL, Piekarz R, Bates S. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma. 2017 Oct;58(10):2335-2341. doi: 10.1080/10428194.2017.1295143. Epub 2017 Mar 7.
Public notes

Contacts
Principal investigator
Name 0 0
Lawrence E. Flaherty, MD
Address 0 0
Barbara Ann Karmanos Cancer Institute
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Contact person for public queries
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00546416