Synergy of Pembrolizumab Anti-PD-1 Immunotherapy With Chemotherapy for Poorly Chemo-responsive Thyroid and Salivary Gland Tumors. The iPRIME Study.
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Thyroid Cancer
- Sponsor
- University of Chicago
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Rate of response
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
Phase II, 2-cohort, single arm trial treated with the combination of the following two agents:
- Pembrolizumab (MK3475) 200mg, every three weeks, iv
- Docetaxel 75mg/m2, every three weeks, iv
Detailed Description
Eligible patients will be divided into two cohorts. Cohort 1: salivary gland tumors without SOC treatment option Cohort 2: 'aggressive' thyroid cancer without SOC treatment option Both cohorts will undergo a biopsy and will begin immunotherapy plus chemotherapy. Pembrolizumab and steroid sparing taxane: docetaxel will be given every three weeks for 3 to 6 cycles. For accessible tumors only, at week three patients will receive an on-treatment biopsy. Patients will move on to immunotherapy maintenance after completing their cycles. Pembrolizumab will be given every three weeks until disease progression or up to 35 cycles (about 2 years).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed disease that is unresectable and not amenable to curative intent therapy:
- •Cohort A: salivary gland cancers (mucoepidermoid carcinoma, adenocarcinoma, adenoidcystic carcinoma, acinic cell carcinoma, or other histology) originating in salivary glands.
- •Cohort B: thyroid cancer, RAI-refractory and after failure, intolerance to or refusal of anti-antiangiogenic therapy, or with evidence of dedifferentiated or anaplastic histology.
- •ECOG performance status 0 or
- •Consent to undergo on treatment biopsy if tumor is accessible and safe to biopsy
- •Measurable disease per RECIST 1.1, bone only metastatic disease may be allowed on approval from study PI.
- •Life expectancy of greater than 12 weeks.
- •Available tissue for PD-L1 staining (archival or new core needle biopsy at baseline if no archival tissue available). A minimum of 10 slides are required (unless approval from the PI is obtained)
- •Age greater than or equal to 18 years on day of signing informed consent.
- •Demonstrate reasonable organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of prednisone 10mg/24h equivalent, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Has hypersensitivity to pembrolizumab, docetaxel or any of its excipients.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1, or targeted small molecule therapy within 2 weeks prior to study Day 1, or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier, with the exception of lymphopenia or asymptomatic aberrancies of sodium, amylase, lipase or alkaline phosphatase.
- •Has not recovered from prior surgery, chemotherapy or radiation therapy from adverse events due to a previous treatment/administered agent (i.e., ≤ Grade 1 or return to baseline prior to treatment).
- •Note: Subjects with ≤ Grade 2 neuropathy, any grade hearing loss or tinnitus, or typical side effects from radiotherapy 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.
- •Has a known additional 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 or other cancers that are not likely to influence life expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy).
- •Has known active (growing) central nervous system (CNS) metastases and/or carcinomatous meningitis. Prior radiation or resection is acceptable if clinically stable for at least 4 weeks.
Arms & Interventions
Cohort 1: salivary gland tumors without SOC treatment option
All patients will receive pembrolizumab and docetaxel. First pembrolizumab and docetaxel will be given together. After which patients will receive pembrolizumab alone until disease progression or up to 35 cycles (about 2 years).
Intervention: Pembrolizumab
Cohort 1: salivary gland tumors without SOC treatment option
All patients will receive pembrolizumab and docetaxel. First pembrolizumab and docetaxel will be given together. After which patients will receive pembrolizumab alone until disease progression or up to 35 cycles (about 2 years).
Intervention: Docetaxel
Cohort 2: 'aggressive' thyroid cancer without SOC treatment op
All patients will receive pembrolizumab and docetaxel. First pembrolizumab and docetaxel will be given together. After which patients will receive pembrolizumab alone until disease progression or up to 35 cycles (about 2 years).
Intervention: Pembrolizumab
Cohort 2: 'aggressive' thyroid cancer without SOC treatment op
All patients will receive pembrolizumab and docetaxel. First pembrolizumab and docetaxel will be given together. After which patients will receive pembrolizumab alone until disease progression or up to 35 cycles (about 2 years).
Intervention: Docetaxel
Outcomes
Primary Outcomes
Rate of response
Time Frame: From the start of treatment until the first documented record of response, up to 100 months, whichever comes first.
Secondary Outcomes
- Overall rate of survival(From the start of treatment until the first record of death by any cause, up to 100 months, whichever comes first.)
- Rate of progression free survival(From the start of treatment to the first record of disease progression or death by any cause, up to 100 months, whichever comes first.)
- Number of adverse events(Up to 24 months.)