Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas
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|ClinicalTrials.gov Identifier: NCT03042819|
Recruitment Status : Active, not recruiting
First Posted : February 3, 2017
Last Update Posted : May 22, 2019
This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in patients with locally advanced or metastatic soft tissue sarcoma. The purpose of this study is to determine how safe and tolerable the combination is, as well as the best dose of the study drugs in this patient population.
Selinexor (also called KPT-330), works by trapping "tumor suppressor proteins" within the cell and thus causing the cancer cells to die or stop growing.
|Condition or disease||Intervention/treatment||Phase|
|Soft Tissue Sarcoma||Drug: Selinexor Drug: Doxorubicin||Phase 1|
This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in patients with locally advanced or metastatic soft tissue sarcoma.
Patients will be screened for eligibility within 28 days of the start of the study drugs. In addition to standard tests and procedures, research tumor tissue (archival or fresh biopsy) will be collected for collection for pharmacodynamics. Participants will also be asked if they agree to optional biopsies at 6 cycles if their cancer is responding and at disease progression.
Eligible participants will then receive the study drugs in 21 day cycles. Selinexor will be given by mouth and doxorubicin will be given by vein, once a week, for 6 cycles.
Participants will be restaged every 2 cycles. If participants respond to treatment after 6 cycles, they may be able to continue the selinexor alone as a maintenance treatment until progression or unacceptable toxicity.
While receiving the study drug, many of the screening tests will be repeated. Additional tests and procedures include blood sample collection for pharmacokinetics and pharmacodynamics.
When participants stop the study drug permanently for any reason, an end of treatment visit, 28-day follow-up, and long term follow up every 90 days will occur.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Trial of Selinexor Plus Doxorubicin in Advanced Soft Tissue Sarcomas (STS)|
|Actual Study Start Date :||May 16, 2017|
|Estimated Primary Completion Date :||May 16, 2020|
|Estimated Study Completion Date :||November 16, 2020|
Experimental: Selinexor plus Doxorubicin
Selinexor will be given by mouth (orally) once a week:
Dose Level -1 = 40 mg Dose Level 1 (Starting Dose) = 60 mg Dose Level 2 = 80 mg
Doxorubicin will be given by vein (intravenously) at a dose of 75 mg/m2 once every 3 weeks.
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor proteins (TSPs).
Doxorubicin is currently approved for various cancers. Doxorubicin inhibits DNA synthesis and repair by inhibiting topoisomerase II and also by intercalation between base pairs on the DNA helix. These actions result in the blockade of DNA and RNA synthesis and fragmentation of DNA.
- To evaluate the Incidence of Treatment-Emergent Adverse Events, graded and categorized according to the CTCAE v4.0. [ Time Frame: 3 years ]All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. SAE specific incidence and exact 95% confidence interval will be provided where appropriate.
- To determine the recommended phase II dose (RP2D) of Selinexor in combination with doxorubicin [ Time Frame: 3 years ]The RP2D will be determined according to interim mTPI monitoring algorithm (Figure 5.1) using the dose determining set.
- Rate of Grade 3 Toxicities [ Time Frame: 3 years ]
- Response Rate [ Time Frame: 3 years ]
- Progression-free Survival Rate [ Time Frame: 3 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03042819
|Princess Margaret Cancer Centre|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Albiruni Razak, M.D.||Princess Margaret Cancer Centre|