Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas

NCT02978859 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAQ8661
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.

Conditions

Liposarcoma; Metastatic Liposarcoma

Keywords

MGCD516; Sarcoma; Liposarcoma; Unresectable Liposarcoma; Metastatic Liposarcoma; Sitravatinib

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Were Progression Free

  The number of patients alive and without evidence of disease progression per RECIST criteria v1.1 at the 12-week scan after starting treatment.

  12 weeks

Secondary Outcomes (4)

• Number of Participants Who Experienced a Treatment-related Adverse Event

  12 weeks

• Overall Response Rate (ORR) of MGCD516

  Up to 33 months

• Progression Free Survival (PFS)

  Up to 33 months

• Overall Survival (OS)

  Up to 33 months

Study Arms (1)

MGCD516

EXPERIMENTAL

Patients with locally advanced and unresectable or metastatic sarcoma will receive MGCD516 at the discretion of the principal investigator until disease progression, unacceptable toxicity or adverse event(s) or withdrawal of consent.

Drug: MGCD516

Interventions

MGCD516 DRUG

Administered at 150 mg orally, daily, in continuous 21 day cycles. An orally available, potent small molecular inhibitor of several related receptor tyrosine kinases.

Also known as: Sitravatinib

MGCD516

Eligibility Criteria

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

You may qualify if:

• Stage 1, histologically confirmed well-differentiated or de-differentiated liposarcoma. If stage 1 of the Simon II stage design fails to meet its endpoint for liposarcoma patients, an additional 16 patients will be enrolled, composed of 4 each of MPNST, synovial sarcoma, alveolar rhabdomyosarcoma and alveolar soft part sarcoma (otherwise, an additional 16 patients with well-differentiated or de-differentiated liposarcoma would be enrolled). Pathology review occurs at the center enrolling the patient on this trial.
• Disease must be locally advanced and unresectable or metastatic. Disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligible.
• Patients must have measurable disease by RECIST criteria version 1.1.
• Patients must evidence of disease progression, either clinically or radiographically,within the 8 weeks prior to study enrollment, as determined by the principal investigator.
• Patients must have been treated with at least one prior systemic regimen for sarcoma. Adjuvant systemic therapy qualifies as prior therapy for the purposes of this study. There is no upper limit on previous lines of therapy received. A prior line of systemic therapy may include prior investigational agents received as part of other clinical studies.
• Patients must be age 18 years or older. Because no dosing or adverse event data are currently available for MGCD516 in patients less than 18 years of age, children are excluded from the present study, but will be eligible for future pediatric trials.
• Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must demonstrate normal organ and marrow function.
• Patients must demonstrate adequately controlled blood pressure at the time of study entry, as defined by a blood pressure ≤ 150/100 mmHg at study screening on at least one of two screenings conducted at least 24 hours apart. If blood pressure meets these guidelines on initial measurement, no subsequent measurement for screening is needed. Blood pressure may be assessed by automated or manual methods by an appropriately trained clinician or nurse.
• Patients must have normal left ventricular systolic function, as demonstrated by a transthoracic echocardiogram or multigated acquisition (MUGA) scan showing a normal left ventricular ejection fraction.
• Women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Patients must not have received treatment with any chemotherapy, immunotherapy, radiotherapy or an investigational agent for malignancy within the 28 days preceding study registration. Patients may not have received treatment with nitrosureas or mitomycin within the 42 days prior to study registration. Patients may not have received treatment with a small molecule targeted agent (including off-label or investigational use) within 14 days preceding study registration, provided this represents at least 7 half-lives for that agent. Toxic effects from any prior therapy (except alopecia) must have resolved to grade 1 or less according to NCI CTCAE v4.0 or to the patient's baseline by the time of registration.
• Patients may not be receiving any other investigational agent for any purpose concurrently. Patients may not require ongoing treatment with (a) gastric pH modifying medications including proton pump inhibitors or H2 blockers (patients may switch to antacids), (b) medications which are known to be sensitive substrates or substrates with a narrow therapeutic index for the P-gp and breast cancer resistance protein (BCRP) transporters and/or (c) medications known to cause corrected QT Interval (QTc) prolongation with risk of Torasades. Please see Appendix 1 for a list of such prohibited concomitant medications at study entry.
• Patients with brain metastases which are symptomatic may not be enrolled. Those subjects with untreated brain metastases ≤ 1 cm may who are asymptomatic and for whom there are no plans for surgery, radiation or corticosteroid use may be considered eligible at the discretion of the principal investigator. Subjects with brain metastases that have been treated and are stable for at least 1 month are eligible if they are asymptomatic and not receiving corticosteroids.
• Patients may not have a history of allergic reaction or hypersensitivity to microcrystalline cellulose (Avicel PH302) or polysorbate 80 (Tween 80), which are components of the drug product MGCD516.
• Patients may not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled diabetes mellitus or uncontrolled psychiatric illness that would limit compliance with study requirements in the opinion of the principal investigator. Additionally, patients must be free of any impairment in the ability to swallow and absorb the oral study drug.
• Patients may not be pregnant or nursing. Pregnant women are excluded from this study because the teratogenic effects of MGCD516 have not been adequately studied. A negative pregnancy test must be documented 7 days or less prior to registration. Because there is an unknown but potential risk for adverse events to nursing infants secondary to treatment of the mother with MGCD516, breastfeeding must be discontinued prior to registration for this clinical trial.
• Patients may not have known HIV infection. HIV-positive patients on combination.

Sponsors & Collaborators

• Columbia University: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (3)

Massachussetts General Hospital

Boston, Massachusetts, 02114-2696, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Liposarcoma; Sarcoma

Interventions

sitravatinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Benjamin Izar
• Organization: Columbia University

bi2175@cumc.columbia.edu

212 304 5871

Study Officials

• Benjamin Izar, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 1, 2016
• Study Start: November 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: December 20, 2021
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)