LiposarcomaPhase 2NCT02978859
Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas
A Phase 2 study testing MGCD516 in people with Liposarcoma and Metastatic Liposarcoma, run by Columbia University at 3 sites in United States.
Trial summary
The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liposarcoma, Metastatic Liposarcoma
- What is being tested?
- MGCD516
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2016to 20 Dec 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachussetts General Hospital
Boston, Massachusetts, 02114-2696
Columbia University Irving Medical Center
New York, New York, 10032
Washington University
St Louis, Missouri, 63130
About this study
Official title: A Phase II Trial of Sitravatinib (MGCD516), a Multi-receptor Tyrosine Kinase Inhibitor, in Advanced Liposarcoma and Other Soft Tissue Sarcomas
The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.
Read the detailed description
Sarcomas are a group of cancers which arise from connective tissue and bone, of which more than 50 subtypes exist. Approximately 12,000 people are diagnosed with sarcoma annually in the United States.
Liposarcoma is one of the more common types of soft tissue sarcoma. The primary treatment for liposarcoma is surgery when possible. When liposarcoma is not amenable to surgery, various systemic treatments, including chemotherapy, are used. However, the effectiveness of existing treatments for liposarcoma is limited.
Sitravatinib is an oral, targeted drug which inhibits receptor tyrosine kinases. Receptor tyrosine kinases are proteins on the surface of the liposarcoma cell which play a role in cancer growth. In laboratory work, Sitravatinib effectively suppressed the growth of liposarcoma models. The purpose of this study is to evaluate the safety and efficacy of Sitravatinib in patients with liposarcoma which cannot be removed by surgery.
- Conditions
- Liposarcoma, Metastatic Liposarcoma
- Being tested
- MGCD516
- Keywords
- MGCD516, Sarcoma, Liposarcoma, Unresectable Liposarcoma, Metastatic Liposarcoma, Sitravatinib
- Medical subject headings
- Liposarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MGCD516Drug
Also called Sitravatinib
Administered at 150 mg orally, daily, in continuous 21 day cycles. An orally available, potent small molecular inhibitor of several related receptor tyrosine kinases.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MGCD516 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (4)
Number of Participants Who Experienced a Treatment-related Adverse Event
Measured: 12 weeks
Overall Response Rate (ORR) of MGCD516
The ORR was defined as the number of patients having a best objective tumor status of complete or partial response per RECIST v1.1 criteria lasting at least 4 weeks divided by the number of evaluable patients.
Measured: Up to 33 months
Progression Free Survival (PFS)
PFS was defined from the date of enrollment to the date of progression or death, the last progression-free scan for patients who withdrew consent or had unexpected adverse events, or the last follow-up for patients who withdrew consent prior to the first scan, whichever occurred first.
PFS and OS were estimated using the Kaplan-Meier method.
Measured: Up to 33 months
Overall Survival (OS)
OS was defined from the date of enrollment to the date of death or last follow-up, whichever occurred first.
PFS and OS were estimated using the Kaplan-Meier method.
Measured: Up to 33 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2016 (estimated)
- Study startNov 2016
- Primary completionJan 2020
- Study completion20 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LiposarcomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Mirati Therapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Benjamin Izar, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02978859
- Sponsor's protocol ID
- AAAQ8661
- Status last verified
- Jul 2024
- First submitted
- 29 Nov 2016
- Last updated
- 18 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Sitravatinib (MGCD516), a Multi-receptor Tyrosine Kinase Inhibitor, in Advanced Liposarcoma and Other Soft Tissue Sarcomas
- ClinicalTrials.gov ID
- NCT02978859
- Acronym / sponsor ID
- AAAQ8661
- Conditions
- Liposarcoma, Metastatic Liposarcoma
- Keywords
- MGCD516, Sarcoma, Liposarcoma, Unresectable Liposarcoma, Metastatic Liposarcoma, Sitravatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Mirati Therapeutics Inc.
- Study start
- Nov 2016 (actual)
- Primary completion
- Jan 2020 (actual)
- Study completion
- 20 Dec 2021 (actual)
- First posted
- 1 Dec 2016 (estimated)
- Results
- Posted 18 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.
Detailed description
Sarcomas are a group of cancers which arise from connective tissue and bone, of which more than 50 subtypes exist. Approximately 12,000 people are diagnosed with sarcoma annually in the United States.
Liposarcoma is one of the more common types of soft tissue sarcoma. The primary treatment for liposarcoma is surgery when possible. When liposarcoma is not amenable to surgery, various systemic treatments, including chemotherapy, are used. However, the effectiveness of existing treatments for liposarcoma is limited.
Sitravatinib is an oral, targeted drug which inhibits receptor tyrosine kinases. Receptor tyrosine kinases are proteins on the surface of the liposarcoma cell which play a role in cancer growth. In laboratory work, Sitravatinib effectively suppressed the growth of liposarcoma models. The purpose of this study is to evaluate the safety and efficacy of Sitravatinib in patients with liposarcoma which cannot be removed by surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MGCD516 | Experimental | Drug: MGCD516Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MGCD516Also: SitravatinibAdministered at 150 mg orally, daily, in continuous 21 day cycles. An orally available, potent small molecular inhibitor of several related receptor tyrosine kinases. | Drug | MGCD516 |
Primary outcome
Number of Participants Who Were Progression Free
Time frame: 12 weeks
The number of patients alive and without evidence of disease progression per RECIST criteria v1.1 at the 12-week scan after starting treatment.
4 secondary outcomes
Number of Participants Who Experienced a Treatment-related Adverse Event
Time frame: 12 weeks
Overall Response Rate (ORR) of MGCD516
Time frame: Up to 33 months
Progression Free Survival (PFS)
Time frame: Up to 33 months
Overall Survival (OS)
Time frame: Up to 33 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Izar, MD principal investigator
Columbia University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MGCD516 in people with Liposarcoma and Metastatic Liposarcoma, run by Columbia University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Were Progression Free (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2024.