Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas

NCT02636725 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20150932
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test if Axitinib together with Pembrolizumab can slow tumor growth and know the side effects of the combination treatment.

Conditions

Alveolar Soft Part Sarcoma; Soft Tissue Sarcomas

Keywords

Advanced Alveolar Soft Part Sarcoma; ASPS; STS

Outcome Measures

Primary Outcomes (1)

• Percentage of Evaluable Participants Achieving Progression-Free Survival (PFS) at 3 Months

  Percentage of participants who are disease progression free 3 months after initiation of therapy. Disease progression will be evaluated from imaging measures using the Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.

  3 Months

Secondary Outcomes (5)

• Percentage of Evaluable Participants Achieving Objective Response Rate (ORR)

  Up to 2 Years

• Percentage of Evaluable Participants Achieving Clinical Benefit Response (CBR)

  Up to 2 Years

• Time to Progression (TTP)

  Up to 2 years

• Overall Survival (OS)

  Up to 5 years

• Number of Participants Experiencing Serious Adverse Events (SAEs), Dose-Limiting Toxicities, and Grade 3 or Higher Treatment-Emergent Adverse Events

  Up to 25 months

Study Arms (2)

Axitinib Plus Pembrolizumab Group

EXPERIMENTAL

Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Drug: Axitinib; Drug: Pembrolizumab

Axitinib Plus Pembrolizumab Expansion Cohort

EXPERIMENTAL

Expansion cohort for up to 10 additional patients with alveolar soft part sarcoma. Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Drug: Axitinib; Drug: Pembrolizumab

Interventions

Axitinib DRUG

5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Also known as: Inlyta

Axitinib Plus Pembrolizumab Expansion Cohort; Axitinib Plus Pembrolizumab Group

Pembrolizumab DRUG

200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Also known as: MK-3475, Keytruda

Axitinib Plus Pembrolizumab Expansion Cohort; Axitinib Plus Pembrolizumab Group

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed sarcoma with pathology review required for any outside samples.
• The following histologies may be enrolled without prior treatment:
• alveolar soft part sarcoma,
• clear cell sarcoma,
• epithelioid hemangioendothelioma, and
• chordoma.
• The following histologies may be enrolled only if refractory to anthracycline-based chemotherapy or if the patient refuses to undergo standard of care treatment:
• synovial sarcoma,
• rhabdomyosarcoma,
• malignant peripheral nerve sheath tumors,
• dedifferentiated, pleomorphic or myxoid/round cell liposarcoma,
• leiomyosarcoma,
• malignant phylloides tumor,
• high grade undifferentiated pleomorphic sarcomas (HGUPS/MFH),
• angiosarcoma,

You may not qualify if:

• Prior therapy with axitinib. Patients are permitted to have received prior tyrosine kinase inhibitor (TKI) therapy including imatinib, sunitinib, pazopanib, or similar. Patients may have received prior Programmed death 1 (PD-1)/Programmed death-ligand 1 (PD-L1) directed therapy.
• Hypersensitivity to axitinib, pembrolizumab or any of its excipients.
• Patients may not be receiving any other investigational agents (within 4 weeks prior to Cycle 1, day 1).
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Cycle 1, day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1, Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
• Patients with bone-only lesions.
• Patients with underlying immune deficiency, chronic infections including HIV, hepatitis, or tuberculosis (TB) or autoimmune disease.
• Patients with underlying hematologic issues including bleeding diathesis, known previous GI bleeding requiring intervention within the past 6 months, active pulmonary emboli or deep vein thromboses (DVT) that are not stable on anticoagulation regimen.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Concomitant (or receipt of) treatment with medications that may affect the metabolism of pembrolizumab and/or axitinib within 7 days prior to Cycle 1, day 1 of axitinib.
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia

Sponsors & Collaborators

• Jonathan Trent, MD, PhD: lead
• Merck Sharp & Dohme LLC: collaborator
• Pfizer: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (1)

• Wilky BA, Trucco MM, Subhawong TK, Florou V, Park W, Kwon D, Wieder ED, Kolonias D, Rosenberg AE, Kerr DA, Sfakianaki E, Foley M, Merchan JR, Komanduri KV, Trent JC. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol. 2019 Jun;20(6):837-848. doi: 10.1016/S1470-2045(19)30153-6. Epub 2019 May 8.

  PMID: 31078463 RESULT

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part; Sarcoma

Interventions

Axitinib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Arm 2, the Axitinib Plus Pembrolizumab Expansion Cohort, did not open.

Results Point of Contact

• Title: Jonathan Trent MD
• Organization: University of Miami

JTrent@med.miami.edu

305-243-2581

Study Officials

• Jonathan C Trent, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 14, 2015
• First Posted: December 22, 2015
• Study Start: April 19, 2016
• Primary Completion: May 8, 2018
• Study Completion: March 3, 2023
• Last Updated: July 12, 2024
• Results First Posted: November 26, 2021

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)