Nivolumab for Recurrent/Metastatic Carcinosarcoma

Study Overview
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Brief Summary
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Carcinosarcoma is a malignant neoplasm that is composed of both epithelial and mesenchymal elements and aggressive tumor that are staged as high-grade cancer in NCCN guideline. They are regarded as rare aggressive malignancies with a high potential to develop distant metastases and are associated with an overall poor survival. The aggressive nature of this malignancy coupled with a high relapse rate defines a poor clinical course for most patients. First line treatment of patients with advanced uterine carcinosarcoma with paclitaxel plus carboplatin achieved an objective response rate of 54% of patients. For this orphan tumor, carcinosarcoma, as these drugs would hypothetically act only on tissues with overexpression of PD-L1, they theoretically provide a more precise therapeutic effect on tumor cells with considerably less side effects. Therefore, the investigators suggest phase II trial of nivolumab for metastatic/recurred carcinosarcoma who have progressed after prior chemotherapy.

Detailed Description
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Single center, prospective phase II trial.

Official Title
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A Phase II Trial of Nivolumab for Recurrent/Metastatic Carcinosarcoma

Conditions
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Recurrent/Metastatic Carcinosarcoma

Intervention / Treatment
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* Drug: nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed recurrent/metastatic carcinosarcoma ECOG performance status of 0 to 1 ≥ 19 years of age At least 1 prior chemotherapy Patients who have at least 1 measurable disease per the RECIST Guideline Ver. 1.1 as confirmed by imaging within 28 days before randomization Subjects who meet the following criteria: Absolute neutrophil count (ANC) ≥ 1500 /µ Platelet count ≥ 75,000/ µL Serum creatinine < 1.5 x upper limit of normal (ULN) AST (SGOT) and ALT (SGPT) < 3 x upper limit of normal (ULN) (If there is Liver Metastasis < 5 x upper limit of normal (ULN)) Total bilirubin < 1.5 x upper limit of normal (ULN) Exclusion Criteria: More than 4 prior cytotoxic agents Prior treatment with systemic PD-L1-directed therapy Patient who has had chemotherapy, radiotherapy, or biological therapy within 2 weeks prior to entering the study, or who has not recovered from the adverse events due to previous agents administered more than 2 weeks prior to study day Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms Patients with multiple primary cancers (with the exception of completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, or superficial bladder cancer, or any other cancer that has not recurred for at least 3 years) History of active non-infectious pneumonitis requiring treatment with steroids, or history or current signs of chronic interstitial lung disease Known active infection

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nivolumab<br> | Drug: nivolumab<br>* nivolumab 3mg/kg (every 2 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free rate (PFR) at 6 months | proportion of patients who did not progress and were alive at 24 weeks (RECIST version 1.1) | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) by RECIST version 1.1 |  | 8 weeks | 
| Progression-free survival (PFS) by RECIST version 1.1 |  | 8 weeks | 
| Overall survival (OS) |  | 8 weeks | 
| Time to progression (TPP) |  | 8 weeks | 
| Drug toxicity and safety analysis by CTCAE Version 5 |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carcinosarcoma, nivolumab