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Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas

Primary Purpose

Soft Tissue Sarcoma

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Selinexor

Doxorubicin

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent
Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Age ≥ 18 years.
Patients must have histologically confirmed locally advanced/unresectable or metastatic soft tissue sarcoma.
Patients must have not received prior doxorubicin.
Patient must show evidence of progressive disease on study entry or newly diagnosed patients with de novo metastatic measurable disease
Patient must have measureable disease as defined by RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Adequate hematopoietic function
Adequate hepatic function:
Adequate renal function
Adequate cardiac function13
Patients must agree to use methods of contraception as a agreed upon by the patient and study doctor

Exclusion Criteria:

Patient is pregnant or lactating
Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy.
Major surgery within 4 weeks before initiation of therapy
Unstable cardiovascular function
Active, ongoing or uncontrolled active infection within one week prior to first dose.
Malignancies other than disease under study within 2 years prior to Cycle 1, Day 1.
Known to be HIV seropositive
Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B virus (HBV) surface antigen (HBsAg)
Patients with active CNS malignancy.
Patients with any gastrointestinal dysfunctions that could interfere with the absorption of Selinexor or patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
Inability or unwillingness to take supportive medications such as anti-nausea and anti anorexia agents.
In the opinion of the Investigator, patients who are significantly below their ideal body weight
Serious psychiatric or medical conditions that could interfere with treatment
Concurrent therapy with approved or investigational anticancer therapeutic agents
Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results

Sites / Locations

Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Selinexor plus Doxorubicin

Arm Description

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.

Outcomes

Primary Outcome Measures

To evaluate the Incidence of Treatment-Emergent Adverse Events, graded and categorized according to the CTCAE v4.0.

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

The RP2D will be determined according to interim mTPI monitoring algorithm (Figure 5.1) using the dose determining set.

Secondary Outcome Measures

Rate of Grade 3 Toxicities

Response Rate

Progression-free Survival Rate

Full Information

NCT ID

NCT03042819

First Posted

February 1, 2017

Last Updated

November 26, 2021

Sponsor

University Health Network, Toronto

Collaborators

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT03042819

Brief Title

Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas

Official Title

A Phase 1b Trial of Selinexor Plus Doxorubicin in Advanced Soft Tissue Sarcomas (STS)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Completed

Study Start Date

May 16, 2017 (Actual)

Primary Completion Date

November 30, 2019 (Actual)

Study Completion Date

June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

Collaborators

Karyopharm Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Soft Tissue Sarcoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Selinexor plus Doxorubicin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Selinexor

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

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.

Primary Outcome Measure Information:

Title

To evaluate the Incidence of Treatment-Emergent Adverse Events, graded and categorized according to the CTCAE v4.0.

Description

Time Frame

3 years

Title

To determine the recommended phase II dose (RP2D) of Selinexor in combination with doxorubicin

Description

The RP2D will be determined according to interim mTPI monitoring algorithm (Figure 5.1) using the dose determining set.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Rate of Grade 3 Toxicities

Time Frame

3 years

Title

Response Rate

Time Frame

3 years

Title

Progression-free Survival Rate

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Age ≥ 18 years. Patients must have histologically confirmed locally advanced/unresectable or metastatic soft tissue sarcoma. Patients must have not received prior doxorubicin. Patient must show evidence of progressive disease on study entry or newly diagnosed patients with de novo metastatic measurable disease Patient must have measureable disease as defined by RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Adequate hematopoietic function Adequate hepatic function: Adequate renal function Adequate cardiac function13 Patients must agree to use methods of contraception as a agreed upon by the patient and study doctor Exclusion Criteria: Patient is pregnant or lactating Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy. Major surgery within 4 weeks before initiation of therapy Unstable cardiovascular function Active, ongoing or uncontrolled active infection within one week prior to first dose. Malignancies other than disease under study within 2 years prior to Cycle 1, Day 1. Known to be HIV seropositive Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B virus (HBV) surface antigen (HBsAg) Patients with active CNS malignancy. Patients with any gastrointestinal dysfunctions that could interfere with the absorption of Selinexor or patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. Inability or unwillingness to take supportive medications such as anti-nausea and anti anorexia agents. In the opinion of the Investigator, patients who are significantly below their ideal body weight Serious psychiatric or medical conditions that could interfere with treatment Concurrent therapy with approved or investigational anticancer therapeutic agents Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Albiruni Razak, M.D.

Organizational Affiliation

Princess Margaret Cancer Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas

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