Nivolumab for Recurrent/Metastatic Carcinosarcoma

A Phase II Trial of Nivolumab for Recurrent/Metastatic Carcinosarcoma

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent/Metastatic Carcinosarcoma
• Intervention / Treatment: Drug: nivolumab

Detailed Description

Single center, prospective phase II trial.

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyo Song Kim; Phone Number: 82-2-2228-8124; Email: hyosong77@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
    • Contact: Hyo Song Kim; Phone Number: 82-2-2228-8124; Email: hyosong77@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nivolumab	Drug: nivolumab; nivolumab 3mg/kg (every 2 weeks)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: February 3, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: nivolumab; carcinosarcoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Neoplasms, Complex and Mixed; Sarcoma; Recurrence; Carcinosarcoma; Mixed Tumor, Mullerian; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 4-2019-1104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No