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Alveolar Soft Part SarcomaPhase 2NCT02636725

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

A Phase 2 study testing Axitinib and Pembrolizumab in people with Alveolar Soft Part Sarcoma and Soft Tissue Sarcomas, run by Jonathan Trent, MD, PhD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
Axitinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteUnited States
Study dates
19 Apr 2016to 3 Mar 2023
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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,
  • spindle cell sarcoma, not otherwise specified (NOS)
  • malignant myoepithelioma.
  • The following histologies may be enrolled only if refractory to at least one line of chemotherapy or if the patient refuses to undergo standard of care treatment:
  • solitary fibrous tumor/hemangiopericytoma.
  • The following histologies may be enrolled only if refractory to at least first-line targeted therapy or if the patient refuses to undergo standard of care treatment:
  • gastrointestinal stromal tumors,
  • extraskeletal myxoid chondrosarcoma,
  • PEComa.
  • Primary tumors of bone including Ewing's sarcoma, osteosarcoma, and dedifferentiated chondrosarcoma may only be enrolled if there are measurable target lesions occurring in soft tissue and they are refractory to standard of care anthracycline-based chemotherapy.
  • Any other histology or standard of care therapy not specifically addressed will be reviewed by the principal investigator and pathologist for final determination of eligibility.
  • Measurable disease as defined by RECIST v1.1.
  • Radiographic progression as defined by RECIST v1.1, based on comparison between two radiographic studies no greater than 6 months apart.
  • Inability to undergo complete resection of the disease by surgery.
  • Adequate organ function as defined:
  • Hematological
  • Absolute neutrophil count (ANC) ≥1,000 / microliter (mcL)
  • Platelets ≥75,000 / mcL
  • Hemoglobin ≥8 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Renal
  • Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. (GFR can also be used in place of creatinine or CrCl). Creatinine clearance should be calculated per institutional standard.
  • Hepatic
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN.
  • Aspartate Aminotransferase (AST/SGOT) and Alanine Transaminase (ALT/SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases.
  • Albumin >2.5 mg/dL
  • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Age ≥ 16 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Patients must consent and be willing to undergo three core needle biopsies at baseline, prior to starting Cycle 3, and at off-study. At least one tumor site must be amenable to biopsy in the judgment of the interventional radiologist.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Females of child bearing potential that are sexually active must agree to either practice 2 medically accepted highly effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 120 days after the last dose of study drug. See Appendix G for protocol-approved highly effective methods of contraceptive combinations. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Negative test for pregnancy is required of females of child-bearing potential; A female of child bearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1. has not undergone a hysterectomy or bilateral oophorectomy; or 2. has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months or 730 days).
  • Conception while on treatment must be avoided
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Prior history of vasectomy does NOT replace requirement for contraceptive use.
  • Suitable venous access to allow for all study related blood sampling
  • Ability to understand and willingness to sign a written informed consent document.
  • For minors that are 16 to 18 years of age, assent and parental (or legally acceptable representative) written informed consent must be obtained.

Who cannot join

  • 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.
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  • Patients with end-organ dysfunction as defined in inclusion criterion (i.e. #11 above).
  • 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
  • Prolonged corrected QT (QTc) interval on Screening EKG >475 ms.
  • Ejection Fraction <40% by 2D echocardiogram (ECHO) at Screening.
  • Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Miami

    Miami, Florida, 33136

Other trials in United States

About this study

Official title: A Phase II Trial of Concurrent Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma (ASPS) and Other Soft Tissue Sarcomas (STS)

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.

Read the detailed description

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

Being tested
Axitinib, Pembrolizumab
Keywords
Advanced Alveolar Soft Part Sarcoma, ASPS, STS
Medical subject headings
Sarcoma, Alveolar Soft Part, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AxitinibDrug

    Also called Inlyta

    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.

  • PembrolizumabDrug

    Also called MK-3475, Keytruda

    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.

Study groups in NCT02636725
Study groupRoleWhat they receive
Axitinib Plus Pembrolizumab GroupExperimentalParticipants 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.
Receives: Drug: Axitinib; Drug: Pembrolizumab
Axitinib Plus Pembrolizumab Expansion CohortExperimentalExpansion 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.
Receives: Drug: Axitinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 3 Months

Secondary outcomes (5)

  1. Percentage of Evaluable Participants Achieving Objective Response Rate (ORR)

    Objective Response Rate (ORR) is defined as achieving complete response (CR) or partial response (PR) from imaging measures using (RECIST) 1.1.

    Measured: Up to 2 Years

  2. Percentage of Evaluable Participants Achieving Clinical Benefit Response (CBR)

    CBR is defined as achieving complete response (CR), partial response (PR) or stable disease (SD) from imaging measures using (RECIST) 1.1.

    Measured: Up to 2 Years

  3. Time to Progression (TTP)

    Time to progression (TTP) is defined as time from treatment initiation until documented disease progression according to Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1) or death (by any cause, in the absence of progression). In progression-free patients, PFS will be censored at the last evaluable tumor assessment.

    Measured: Up to 2 years

  4. Overall Survival (OS)

    OS is (OS) is defined as the time from treatment initiation to death from any cause, whichever is earlier. Participants alive or those lost to follow-up will be censored at the last date of contact (or last date known to be alive).

    Measured: Up to 5 years

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

    The number of participants experiencing serious adverse events (SAEs), dose-limiting toxicities (DLTs), and grade 3 or higher treatment-emergent adverse events (AEs). AEs, SAEs and DLTs will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. Treatment-emergent adverse events are those found to be definitely, probably and possibly related to study therapy.

    Measured: Up to 25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2015 (estimated)
  2. Study start19 Apr 2016
  3. Primary completion8 May 2018
  4. Study completion3 Mar 2023

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02636725
Sponsor's protocol ID
20150932
Status last verified
Jul 2024
First submitted
14 Dec 2015
Last updated
12 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31078463

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Axitinib and Pembrolizumab in people with Alveolar Soft Part Sarcoma and Soft Tissue Sarcomas, run by Jonathan Trent, MD, PhD at 1 site 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 53 inclusion and 20 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 12 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 1 site 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 26 Nov 2021). 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?

Percentage of Evaluable Participants Achieving Progression-Free Survival (PFS) at 3 Months (time frame: 3 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02636725, which also lists 1 linked publication.

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 12 Jul 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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