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Trial registered on ANZCTR


Registration number
ACTRN12614001328662
Ethics application status
Approved
Date submitted
25/11/2014
Date registered
17/12/2014
Date last updated
19/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of KPT-330 in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) and Cutaneous T cell Lymphoma (CTCL)
Scientific title
A Multi-center, Phase II, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) and Cutaneous T cell Lymphoma (CTCL)
Secondary ID [1] 285709 0
KCP-330-013
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)
 293579 0
Relapsed or Refractory Cutaneous T cell Lymphoma (CTCL)
 293662 0
Condition category
Condition code
Cancer 293862 293862 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 293863 293863 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral selinexor tablet 100 mg or 80 mg taken on Days 1 and 3 of Weeks 1-3 of each 4-week [28 day] cycle [6 doses per cycle] until disease progression or intolerability.
Participants with a Body Surface Area (BSA) of 1.7 or greater will be given 100mg of selinexor. Participants with a BSA less than 1.7 and greater than or equal to 1.35 will be given 80mg of selinexor.

Oral Dexamethasone tablet (12mg or 8mg in participants with intolerance) will be given with each dose of selinexor.

To minimise nausea, all participants will be given anti-nausea medication (e.g. ondansetron 8 mg tablet
or equivalent) starting on Day 1 before the first dose of
selinexor and continued twice or three times a day as needed.

Participants will be asked to return all the provided study medication at each study visit. The study site staff will account for the number of tablets dispensed against those return by the participant.
Intervention code [1] 290658 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293644 0
To determine selinexor overall disease response rate.

For PTCL patients, disease response will be evaluated by scheduled PET-CT /PET/MRI scans and tumour measurements every 8 weeks.

For CTCL patients, disease response will be assessed using physical examination and skin assessment every 4 weeks.
Timepoint [1] 293644 0
For PTCL patients- Every 8 weeks until disease progression or death

For CTCL patients - Every 4 weeks until disease progression or death
Secondary outcome [1] 311513 0
To determine selinexor duration of response. This will be done by calculating the duration from when the participant has a disease response.

For PTCL patients, disease response will be evaluated by scheduled PET-CT /PET/MRI scans and tumour measurements every 8 weeks.

For CTCL patients, disease response will be assessed using physical examination and skin assessment every 4 weeks.
Timepoint [1] 311513 0
For PTCL patients- Every 8 weeks until disease progression or death

For CTCL patients - Every 4 weeks until disease progression or death
Secondary outcome [2] 311529 0
To characterise the tolerability and safety of selinexor.
This will done by collection of adverse events physical examination and laboratory test and vital sign monitoring. Participants will be questioned regarding adverse events at each visit.
Possible adverse events include: nausea, fatigue, loss of appetite, vomiting, low platelet count, diarrhea, low sodium levels, change in taste, weight loss.
Timepoint [2] 311529 0
At each study visit until disease progression or death
Secondary outcome [3] 311696 0
To determine selinexor disease control rate.
This will be done by calculating the disease control rate over time from when the participant has a disease response.

For PTCL patients, disease response will be evaluated by scheduled PET-CT /PET/MRI scans and tumour measurements every 8 weeks.

For CTCL patients, disease response will be assessed using physical examination and skin assessment every 4 weeks.
Timepoint [3] 311696 0
For PTCL patients- Every 8 weeks until disease progression or death

For CTCL patients - Every 4 weeks until disease progression or death
Secondary outcome [4] 311771 0
To determine selinexor progression free survival.
This will be done by calculating the duration of progression free survival from when the participant has a disease response.

For PTCL patients, disease response will be evaluated by scheduled PET-CT /PET/MRI scans and tumour measurements every 8 weeks.

For CTCL patients, disease response will be assessed using physical examination and skin assessment every 4 weeks.
Timepoint [4] 311771 0
For PTCL patients- Every 8 weeks until disease progression or death

For CTCL patients - Every 4 weeks until disease progression or death
Secondary outcome [5] 311772 0
To determine selinexor overall survival.

This will be done by calculating the overall survival duration of the participant.

Survival follow up will be done via a telephone call to the participant every 3 months until death.
Timepoint [5] 311772 0
Every 3 months until death
Secondary outcome [6] 311773 0
To determine the time to progression for selinexor.

This will be done by calculating the time to progression of disease.

For PTCL patients, disease response will be evaluated by scheduled PET-CT /PET/MRI scans and tumour measurements every 8 weeks.

For CTCL patients, disease response will be assessed using physical examination and skin assessment every 4 weeks.
Timepoint [6] 311773 0
For PTCL patients- Every 8 weeks until disease progression or death

For CTCL patients - Every 4 weeks until disease progression or death

Eligibility
Key inclusion criteria
1. Adult patients 18 years of age or older and providing informed consent
2. ECOG performance status of less than or equal to 2.
3. Relapsed or refractory to previous treatment of PTCL/CTCL
4. Acceptable organ function
5. Non pregnant or not breastfeeding
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known active central nervous system (CNS) lymphoma.
2. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (except glucocorticoids) less than 4 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.
3. Have not adequately recovered from the side effects of previous antineoplastic agents prior to dosing.
4. Active graft-versus-host disease after allogeneic stem cell transplantation.
5. Autologous stem cell transplantation less than 100 days prior to Cycle 1 Day 1
6. Concurrent therapy with approved or investigational anti-cancer drugs
7. Major surgery within last 2 weeks
8. Any other significant concomitant illness
9. Unstable cardiovascular function
10. Uncontrolled infection
11. Active HIV or hepatitis infection
12. Serious psychiatric or medical condition
13. Unable to swallow capsules

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)
Participants will undergo screening assessments up to 30 days before the first dosing (Day 1) of Cycle 1. If the participant meets all the inclusion and none of the exclusion criteria the participant will be enrolled into the study. The dose of selinexor is based on the Body surface area (BSA) of the participant. If BSA is greater than or equal to 1.7, the participant will receive 100mg of selinexor. If the BSA is less than 1.7 m2 and greater than or equal to 1.35 m2, the participant will receive 80mg of selinexor.
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
Single group
Other design features
Nil
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All patients who receive at least one dose of study drug will be included in the analyses, including those who withdraw prematurely from the study.

Hypothesis testing will be used for the primary efficacy endpoint data, in order to evaluate if selinexor provides statistically significant improvement in efficacy over a
minimally acceptable level of 20%. No formal hypothesis testing will be used for other study data, such as demographics and safety data.

Tabulations will be produced for appropriate disposition, demographic, baseline, efficacy and safety parameters. For categorical variables, summary tabulations of the number and percentage of patients within each category (with a category for missing data) of the parameter will be presented, as well as two-sided 95% confidence intervals (CI), unless otherwise stated. For continuous variables, the number of patients, mean, median, standard deviation, minimum, and maximum values will be presented. Time-to- event data will be summarized using Kaplan-Meier (KM) methodology using 25th, 50th (median), and 75th percentiles with associated 2-sided 95% CIs, as well as percentage of censored observations.

Approximately 30 patients will be enrolled. It is planned to enroll up to 10 patients with CTCL; the remaining patients may have PTCL or CTCL. The sample size of this study was not determined by formal statistical calculation.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
27/01/2015
Actual
11/03/2015
Date of last participant enrolment
Anticipated
31/01/2016
Actual
3/09/2015
Date of last data collection
Anticipated
Actual
29/03/2016
Sample size
Target
30
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 3177 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 3178 0
Westmead Hospital - Westmead
Recruitment hospital [3] 3179 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 3237 0
Cabrini Hospital - Malvern - Malvern
Recruitment postcode(s) [1] 8968 0
2139 - Concord Repatriation Hospital
Recruitment postcode(s) [2] 8969 0
2145 - Westmead
Recruitment postcode(s) [3] 8970 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [4] 9017 0
3144 - Malvern

Funding & Sponsors
Funding source category [1] 290283 0
Commercial sector/Industry
Name [1] 290283 0
Karyopharm Therapeutics Inc.
Country [1] 290283 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Karyopharm Therapeutics Inc.
Address
85 Wells Avenue
Newton, MA 02459
Country
United States of America
Secondary sponsor category [1] 288995 0
None
Name [1] 288995 0
Address [1] 288995 0
Country [1] 288995 0
Other collaborator category [1] 278238 0
Commercial sector/Industry
Name [1] 278238 0
Novotech (Australia) Pty Limited
Address [1] 278238 0
Level 3, 235 Pyrmont Street
Pyrmont NSW 2009
Country [1] 278238 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291984 0
Concord Hospital HREC
Ethics committee address [1] 291984 0
Ground Floor - Building 20, Concord Repatriation General Hospital, Hospital Rd, Concord NSW 2139
Ethics committee country [1] 291984 0
Australia
Date submitted for ethics approval [1] 291984 0
28/10/2014
Approval date [1] 291984 0
14/01/2015
Ethics approval number [1] 291984 0

Summary
Brief summary
This study will determine whether selinexor has any effects against Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL) and Cutaneous T cell Lymphoma (CTCL).

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and Relapsed or Refractory PTCL or CTCL

Study details
This study drug, selinexor, works by trapping “tumour suppressing proteins” within the cell and thus causing the cancer cells to die or stop growing. Selinexor has previously been tested in humans to define a safe dose to be administered. It is not known at this time if selinexor will treat PTCL/CTCL. This study will examine the effects of selinexor on PTCL/CTCL and look at the side-effects.
After signing the consent, participants will undergo screening assessments up to 30 days before the first dosing. These include: medical and medication history taking, eye examination, ECG, Echocardiogram or MUGA scan, chest X-ray, CT/MRI scans, tumour or skin biopsy, bone marrow aspirate or biopsy, height, weight, vital signs measurement, physical exam, and urine and safety blood tests. Eligible participants will receive oral selinexor tablets on Days 1 and 3 of Weeks 1-3 of each 4-week (28 day) cycle (6 doses/cycle) until disease progression or intolerability. The dose of selinexor will be either 100mg or 80 mg depending on the participants’ body surface area (calculated from their height and weight). Participants will also take dexamethasone to improve selinexor tolerability and antinausea drugs (e.g. ondansetron) to minimise nausea. Additional anti-nausea and anti-anorexia agents may be given as needed. The assessments done at screening will be repeated at various intervals to monitor safety and assess efficacy of the selinexor. In addition, photographs of skin lesions (CTCL patients only) will be taken and blood samples will be taken to check the level of selinexor in the blood at certain timepoints, and to test the binding of selinexor in the blood. Follow-up visits will occur 30 and 60 days after the last dose of selinexor, then participants will be contacted every 3 months to check on their disease status and other treatments.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52950 0
Dr Judith Trotman
Address 52950 0
Concord Repatriation General Hospital
1A Hospital Road, Concord NSW 2139
Country 52950 0
Australia
Phone 52950 0
+612 97675000
Fax 52950 0
Email 52950 0
[email protected]
Contact person for public queries
Name 52951 0
Tracey Marshall
Address 52951 0
Karyopharm Therapeutics
85 Wells Avenue
Newton, MA 02459
Country 52951 0
United States of America
Phone 52951 0
+1617-658-0558
Fax 52951 0
+1617-224-9420
Email 52951 0
[email protected]
Contact person for scientific queries
Name 52952 0
Hagop Youssoufian
Address 52952 0
Karyopharm Therapeutics
85 Wells Avenue
Newton, MA 02459
Country 52952 0
United States of America
Phone 52952 0
+1617-658-0534
Fax 52952 0
+1617-224-9420
Email 52952 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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