A Phase II Trial of Pembrolizumab in Combination With Cisplatin or Carboplatin and Etoposide in Chemotherapy naïve Patients With Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung (Excluding Small Cell) Neuroendocrine Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Neuroendocrine Carcinoma
- Sponsor
- Ochsner Health System
- Locations
- 1
- Primary Endpoint
- Progression Free Survival
- Status
- Withdrawn
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to test the efficacy, safety, and tolerability of the combination of chemotherapy treatment, which could be either Cisplatin or carboplatin and etoposide, and the research study drug, Pembrolizumab (also known as MK-3475) in patients with high grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve. The chemotherapy treatment you receive will be either Cisplatin or carboplatin and etoposide. the participant's doctor will discuss this choice with you and determined which chemotherapy treatment is best for you.
Detailed Description
Combination chemotherapy is the mainstay of treatment for patients with high grade GEPNETs and neuroendocrine carcinomas of the lung. This study will utilize pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus blocks a protective mechanism of cancer cells and thereby allows the immune system to destroy them, in combination with chemotherapy. Combination chemotherapy and pembrolizumab was recently FDA approved and ongoing trials are utilizing this or similar combination with preliminary data demonstrating a promising safety profile.
Investigators
Robert Ramirez
Principal Investigator
Ochsner Health System
Eligibility Criteria
Inclusion Criteria
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be 18 years of age on day of signing informed consent.
- •Must have cytologically or histologically proven high grade neuroendocrine carcinoma of the gastroenteropancreatic system or large cell neuroendocrine carcinoma as defined by the 2010 WHO classification.
- •a. GEPNETs need to have Ki-67 greater than 55%.
- •Have metastatic or unresectable disease.
- •No prior systemic chemotherapy or immunotherapy for metastatic disease allowed.
- •Concurrent use of somatostatin analogs is allowed for symptom control.
- •Life expectancy greater than 12 weeks.
- •Have measurable disease based on RECIST 1.
- •Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day
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 4 weeks of the first dose of treatment.
- •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 history of active TB (Bacillus Tuberculosis)
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had prior systemic anti-cancer therapy for metastatic or unresectable neuroendocrine tumors other than somatostatin analogs.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 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.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation 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 a previously administered agent.
- •Note: 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.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Arms & Interventions
Single Arm
Pembrolizumab 200mg IV day 1 with Carboplatin AUC 6 IV day 1 or Cisplatin 80mg/m2 day 1 with etoposide 100mg/m2 days 1-3 of 21 day cycle. Repeat 4-6 cycles to be followed by maintenance Pembrolizumab 200mg IV day 1 every 21 days until progression or intolerance for up to 2 years.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: 1 year
Assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary Outcomes
- Combination therapy will be safe and tolerable compared to historical controls(Continuous from the signing of the informed consent to 28 days after last study treatment)