Clinical Trials /

Androgen Deprivation Therapy (ADT) and Pembrolizumab for Advanced Stage Androgen Receptor-positive Salivary Gland Carcinoma

NCT03942653

Description:

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.

Related Conditions:
  • Salivary Gland Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Androgen Deprivation Therapy (ADT) and Pembrolizumab for Advanced Stage Androgen Receptor-positive Salivary Gland Carcinoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BTCRC-HN17-111
  • NCT ID: NCT03942653

Conditions

  • Salivary Gland Carcinoma

Interventions

DrugSynonymsArms
Goserelin AcetateGoserelin Acetate + Pembrolizumab
PembrolizumabGoserelin Acetate + Pembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Goserelin Acetate + PembrolizumabExperimentalGoserelin Acetate, 3.6 mg, every four weeks, SQ Pembrolizumab, 200mg, every three weeks, IV
  • Goserelin Acetate
  • Pembrolizumab

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 1.

          -  Adequate organ function as defined below; all screening labs to be obtained within 28
             days prior to registration.

               -  Absolute neutrophil count (ANC) ≥1500/µL

               -  Platelets ≥75,000/µL

               -  Hemoglobin ≥8.0 g/dL or ≥5 mmol/L

               -  Creatinine (Cr) OR Measured or calculated creatinine clearance (GFR can also be
                  used in place of Cr or creatinine clearance) ≤1.5 × ULN OR

                  ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN

               -  Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
                  bilirubin levels >1.5 × ULN

               -  AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver
                  metastases) o International normalized ratio (INR) OR prothrombin time (PT) &
                  aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as
                  PT or aPTT is within therapeutic range of intended use of anticoagulants

          -  A male participant must agree to use contraception during the treatment period and for
             at least 8 months after the last dose of study treatment and refrain from donating
             sperm during this period.

          -  Females of childbearing potential must have a negative serum pregnancy test within 72
             hours prior to registration. NOTE: Females are considered of child bearing potential
             unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
             12 consecutive months

          -  Females of childbearing potential and males with partners of childbearing potential
             must be willing to abstain from heterosexual activity or to use a highly effect form
             of contraception from the time of informed consent until 8 months after treatment
             discontinuation.

          -  As determined by the enrolling physician or protocol designee, ability of the subject
             to understand and comply with study procedures for the entire length of the study

        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 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 within 28 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella (MMR), varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist®) are live attenuated vaccines and are not 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.

          -  Has ≥Grade 3 hypersensitivity to pembrolizumab and/or any of its excipients.

          -  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, levothyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a known history of Human Immunodeficiency Virus (HIV).

          -  Has a known history of active TB (Bacillus Tuberculosis).

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of trial treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:35 months
Safety Issue:
Description:Determine the objective response rate (ORR) of pembrolizumab when given with goserelin in patients with locally recurrent or metastatic androgen receptor-positive salivary gland carcinoma not amenable to curative-intent treatment with surgery or radiation, per RECIST 1.1 Criteria

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:12 Months
Safety Issue:
Description:Determine progression free survival (PFS) at 12 months, according to RECIST 1.1 criteria
Measure:Disease Control Rate
Time Frame:35 Months
Safety Issue:
Description:Disease control rate as defined by stable disease plus objective response (SD+PR+CR), according to RECIST 1.1 criteria
Measure:Overall Survival
Time Frame:12 Months
Safety Issue:
Description:Determine overall survival (OS) at 12 months, according to RECIST 1.1 criteria
Measure:Number of participants with grade 3, 4, 5 adverse events
Time Frame:35 months
Safety Issue:
Description:To evaluate the safety and tolerability of pembrolizumab when given with goserelin, grade 3,4,5 adverse events will be summarized according to CTCAE v5 criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Big Ten Cancer Research Consortium

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