Nivolumab for Recurrent/Metastatic Carcinosarcoma

Phase 2

• Conditions: Recurrent/Metastatic Carcinosarcoma
• Interventions: Drug: nivolumab

• Registration Number: NCT05224999
• Lead Sponsor: Yonsei University

Brief Summary

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

Single center, prospective phase II trial.

Study Timeline

• Study Start: 2019-11-13
• Study First Submitted: 2022-01-24
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-03
• Last Update Submitted: 2022-02-03
• Study First Posted: 2022-02-04
• Last Update Posted: 2022-02-04
• Primary Completion: 2023-01
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Histologically confirmed recurrent/metastatic carcinosarcoma

2. ECOG performance status of 0 to 1

3. ≥ 19 years of age

4. At least 1 prior chemotherapy

5. Patients who have at least 1 measurable disease per the RECIST Guideline Ver. 1.1 as confirmed by imaging within 28 days before randomization

6. 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

1. More than 4 prior cytotoxic agents
2. Prior treatment with systemic PD-L1-directed therapy
3. 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
4. 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
5. 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)
6. History of active non-infectious pneumonitis requiring treatment with steroids, or history or current signs of chronic interstitial lung disease
7. Known active infection

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
nivolumab	nivolumab	-

Primary Outcome Measures

Name	Time	Method
Progression free rate (PFR) at 6 months	at 6 months	proportion of patients who did not progress and were alive at 24 weeks (RECIST version 1.1)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of