Phase II Trial of Androgen Deprivation Therapy (ADT) and Pembrolizumab for Advanced Stage Androgen Receptor-positive Salivary Gland Carcinoma: Big Ten Cancer Research Consortium BTCRC-HN17-111
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Salivary Gland Carcinoma
- Sponsor
- Manish Patel
- Enrollment
- 20
- Locations
- 7
- Primary Endpoint
- Objective Response Rate
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
A Phase II, multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation.
Detailed Description
This is a Phase II multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation. Eligible patients will include both those with no prior systemic therapy and those who have failed prior systemic therapy. Patients who have received previous ADT or immunotherapy will be excluded. ADT will consist of goserelin acetate every 4 weeks with the first injection given approximately 2 weeks prior to the first dose of pembrolizumab. Pembrolizumab 200 mg will be given on day 1 of 21-day cycles, starting 2 weeks after initiation of goserelin acetate. Each 21-day period is considered a treatment cycle with therapy continuing for up to 35 cycles, until disease progression, significant toxicity, or patient refusal. Except for fatigue, we do not expect overlapping toxicities with pembrolizumab and ADT, thus the starting doses will be the FDA-approved doses. This study will use a Simon 2-stage phase II trial design. The first stage of the Simon 2-stage design will have a sample size of nine patients. If at least two patients have an objective response by RECIST 1.1 then enrollment will proceed to stage 2 with an additional 11 patients, to a goal of 20 patients. If less than 4 patients out of 20 respond, then the combination treatment will be rejected. Patients will be staged with CT of neck, chest, abdomen, and pelvis at baseline and every 12 weeks while on study. Treatment with both ADT and pembrolizumab will continue until disease progression or intolerable side effects. Archival tumor biopsy tissue must be available at baseline to evaluate for expression of androgen receptor (AR), PD-L1, and tumor-infiltrating lymphocytes (TIL). An optional biopsy will be performed after 4 doses of pembrolizumab to evaluate immune response to combined therapy. Blood will be collected at baseline, cycle 1 day 1, cycle 2 day 1 and cycle 3 day 1 to evaluate for change in lymphocyte subsets by flow cytometry.
Investigators
Manish Patel
Sponsor-Investigator
Big Ten Cancer Research Consortium
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •Locally advanced, recurrent, or metastatic salivary gland carcinoma that is not amenable to curative surgery or radiation
- •ECOG Performance Status of 0 or 1 within 28 days prior to registration.
- •Local, pathologic testing of androgen receptor-positive salivary gland carcinoma will be performed as standard of care. Archival tissue must be available for central confirmation of androgen receptor-positive disease and for correlative studies. AR positivity will be defined according to IHC staining of tumor tissue with at least 20% of tumor staining positive with moderate intensity (1+ or greater).
- •Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.
- •For patients who have been treated with prior therapy, patients must have documented progression of disease on their prior therapy for entry into the study.
- •Patients with prior chemotherapy, radiation, or surgery as part of curative intent therapy are allowed. Any number of prior lines of systemic therapy is permitted for entry into this study so long as prior therapy did not include anti-androgen therapy or immune checkpoint blockade.
- •If prior cancer treatment, the subject must have recovered from toxic effects of prior cancer treatment (other than alopecia) to ≤ Grade
- •Adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
Exclusion Criteria
- •Women of childbearing age with a positive serum pregnancy test within 72 hours prior to study registration.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
- •Has received prior androgen deprivation therapy including orchiectomy, gonadotropin-releasing hormone (GnRH) agonists/antagonists, androgen receptor blocker, abiraterone, or enzalutamide.
- •Has received prior systemic anti-cancer therapy including investigational agents within 14 days prior to registration.
- •Has had an allogenic tissue or solid organ transplant.
- •Has received prior palliative radiotherapy within 7 days of start of study treatment. Participants must have recovered from all radiation-related toxicities and require less than 10mg of prednisone (or equivalent corticosteroid) daily.
- •Has received a live vaccine or live-attenuated vaccine within 28 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- •Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 14 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
Arms & Interventions
Goserelin Acetate + Pembrolizumab
Goserelin Acetate, 3.6 mg, every four weeks, SQ Pembrolizumab, 200mg, every three weeks, IV
Intervention: Pembrolizumab
Goserelin Acetate + Pembrolizumab
Goserelin Acetate, 3.6 mg, every four weeks, SQ Pembrolizumab, 200mg, every three weeks, IV
Intervention: Goserelin Acetate
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: 35 months
Objective response rate to therapy (complete and partial responses) at 3 month intervals after beginning goserelin and pembrolizumab based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Secondary Outcomes
- Overall Survival(12 Months)
- Assess Adverse Events(35 months)
- Progression Free Survival(12 Months)
- Disease Control Rate(35 Months)