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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00770536




Registration number
NCT00770536
Ethics application status
Date submitted
9/10/2008
Date registered
10/10/2008
Date last updated
29/09/2015

Titles & IDs
Public title
AMG386 Comb w. Either Pegylated Liposomal Doxorubicin or Topotecan Subjects w. Advanced Recurrent Epithelial Ovarian CR
Scientific title
A Phase 1b Study of AMG 386 in Combination With Either Pegylated Liposomal Doxorubicin or Topotecan in Subjects With Advanced Recurrent Epithelial Ovarian Cancer
Secondary ID [1] 0 0
20070182
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Carcinoma 0 0
Fallopian Tube Cancer 0 0
Gynecological Malignancies 0 0
Metastases 0 0
Oncology 0 0
Ovarian Cancer 0 0
Solid Tumors 0 0
Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - A1: AMG 386 10 mg/kg + Liposomal doxorubicin
Treatment: Drugs - A3: AMG 386 15mg/kg + Liposomal doxorubicin
Treatment: Drugs - B1: AMG 386 10 mg/kg + Topotecan
Treatment: Drugs - B3: AMG 386 15mg/kg + Topotecan

Experimental: Part 1 - In part 1, six subjects will be assigned to each cohort A or B. This is a dose escalation/de escalation study with a 6 + 3 design based on the incidence of DLTs (dose limiting toxicities) during the first 4 weeks of combined therapy \[(cohort A: AMG 386 and pegylated liposomal doxorubicin) or (cohort B: AMG 386 and topotecan)\].

Experimental: Part 2 - The decision on declaration of a safe and tolerable dose during part 1 will lead to part 2 (cohort A: liposomal doxorubicin + AMG 386 MTD (max tolerated dose) of part 1, cohort B: Topotecan + AMG 386 MTD (max tolerated dose) of part 1


Treatment: Drugs: A1: AMG 386 10 mg/kg + Liposomal doxorubicin
Liposomal doxorubicin 50 mg/m2 IV Q4W in combination with AMG 386 10 mg/kg IV QW

Treatment: Drugs: A3: AMG 386 15mg/kg + Liposomal doxorubicin
A3: AMG 386 15 mg/kg IV QW + Liposomal doxorubicin 50 mg/m2 IV Q4W

Treatment: Drugs: B1: AMG 386 10 mg/kg + Topotecan
B1: AMG 386 10 mg/kg IV QW + Topotecan 4 mg/m2 IV days 1, 8, 15, of a 28 day dosing schedule

Treatment: Drugs: B3: AMG 386 15mg/kg + Topotecan
AMG 386 15mg/kg IV QW + Topotecan 4mg/m2 IV days 1, 8, 15 of a 28 day dosing schedule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The primary objective is to identify the incidence of adverse events and clinical laboratory abnormalities defined as dose limiting toxicity in subjects treated with AMG 386 + pegylated liposomal doxorubicin (cohort A) and with AMG 386 + topotecan
Timepoint [1] 0 0
first 4 weeks of treatment
Secondary outcome [1] 0 0
To evaluate the treatment effect as measured by: objective response rate (ORR), duration of response (DOR), PFS, change in tumor burden, CA 125 Response and Progression by GCIG and CA-125 duration of response
Timepoint [1] 0 0
Treatment and follow-up phase of study
Secondary outcome [2] 0 0
To evaluate the incidence of adverse events and clinical laboratory abnormalities not defined as DLTs.
Timepoint [2] 0 0
first 4 weeks of treatment
Secondary outcome [3] 0 0
To determine the pharmacokinetics of pegylated liposomal doxorubicin (and its metabolite, doxorubicinol), topotecan and AMG 386 (Cmax, AUC, and Cmin for intensive assessment; Cmax and Cmin for sparse assessment).
Timepoint [3] 0 0
Treatment and follow-up phase of study
Secondary outcome [4] 0 0
To estimate the incidence of anti AMG 386 antibody formation.
Timepoint [4] 0 0
Treatment and follow-up phase of study

Eligibility
Key inclusion criteria
* Histologically or cytologically documented recurrent invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Subjects must have received at least one platinum containing regimen
* Radiographically documented progression per RECIST criteria with modifications or progression of CA 125 as adopted by GCIG during or subsequent to the last chemotherapy regimen
* Subjects may include those with measurable or non measurable disease
* All scans and x-rays used to document measurable or non measurable disease must be done within 28 days prior to enrollment
* Female 18 years of age or older at the time the written informed consent is obtained
* GOG Performance Status of 0 or 1
* Left Ventricular Ejection Fraction (LVEF) >= institutional lower limit of normal for subjects assigned to cohort A only
* Adequate organ function as assessed by laboratory studies (hematological and chemistries)
* Life expectancy >= 3 months (per investigator opinion)
* Subjects of child bearing potential who have not undergone a bilateral salpingo oophorectomy and are sexually active must consent to use an accepted and effective double barrier non hormonal method of contraception from signing the informed consent through 6 months after last dose of study drug
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects believed to be a higher than average risk of bowel perforation. This includes symptoms of partial or complete bowel obstruction, recent (within 6 months) history of fistula or bowel perforation, subjects requiring total parenteral nutrition and continuous hydration
* Previous abdominal /or pelvic external beam radiotherapy
* Known history of central nervous system metastases
* Subjects with a history of prior malignancy, except:

* Malignancy treated with curative intent and with no known active disease present for >= 3 years before study day 1 and felt to be at low risk for recurrence by treating physician
* Adequately treated non melanomatous skin cancer or lentigo maligna without evidence of disease
* Adequately treated cervical carcinoma in situ without evidence of disease
* Prior myeloablative high dose chemotherapy with allogeneic or autologous stem cell (or bone marrow) transplant
* History of arterial or deep venous thromboembolism within 12 months prior to enrollment
* Clinically significant cardiac disease within 12 months prior to enrollment
* Prior treatment with doxorubicin or pegylated liposomal doxorubicin (cohort A subjects) and topotecan (cohort B subjects)
* Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine and tacrolimus

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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 1
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
1/01/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2015
Sample size
Target
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Footscray
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3011 - Footscray
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
North Dakota
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Belgium
State/province [10] 0 0
Liège
Country [11] 0 0
Belgium
State/province [11] 0 0
Liège
Country [12] 0 0
Belgium
State/province [12] 0 0
Wilrijk

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is a 2 part, 2 cohort, open-label, dose escalation/de escalation study of AMG 386 in combination with either pegylated liposomal doxorubicin or topotecan in subjects with recurrent ovarian cancer. Up to 100 subjects will be enrolled to receive AMG 386 in combination with either pegylated liposomal doxorubicin every 4 weeks (cohort A) or topotecan weekly on days 1, 8, and 15 of a 28 day dosing schedule (cohort B). Subject enrollment and assignment to either cohort will be based on eligibility and the investigator's discretion.

It is hypothesized that AMG 386, in combination with each of the chemotherapy regimens: either pegylated liposomal doxorubicin or topotecan will be safe and well tolerated in subjects with recurrent ovarian cancer.
Trial website
https://clinicaltrials.gov/study/NCT00770536
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00770536