Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas

NCT03042819 | Completed Phase 1 DMC

• 1 other identifier: SAR-002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• 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.

  3 years

• 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.

  3 years

Secondary Outcomes (3)

• Rate of Grade 3 Toxicities

  3 years

• Response Rate

  3 years

• Progression-free Survival Rate

  3 years

Study Arms (1)

Selinexor plus Doxorubicin

EXPERIMENTAL

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.

Drug: Selinexor; Drug: Doxorubicin

Interventions

Selinexor DRUG

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).

Selinexor plus Doxorubicin

Doxorubicin DRUG

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.

Selinexor plus Doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Sarcoma

Interventions

selinexor; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Albiruni Razak, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 3, 2017
• Study Start: May 16, 2017
• Primary Completion: November 30, 2019
• Study Completion: June 30, 2021
• Last Updated: December 9, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)