Cabozantinib Plus Nivolumab and Ipilimumab in Women With Recurrent Gynecologic Carcinosarcoma

NCT04149275 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB-300003948
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of Cabozantinib in combination with Nivolumab and Ipilimumab and see what affects that this combination treatment has on those with recurrent carcinosarcomas.

Conditions

Carcinosarcoma of Ovary; Carcinosarcoma of Uterus; Carcinosarcoma of Vagina

Keywords

Cabozantinib; Nivolumab; Ipilimumab; tyrosine-kinase inhibitor; anti-PD-1; anti-CTLA-4

Outcome Measures

Primary Outcomes (1)

• Percent progression free survival according to RECIST v1.1

  To estimate the proportion of patients with recurrent carcinosarcoma, who survive progression-free for at least 6 months, treated with cabozantinib + nivolumab + ipilimumab in the second-line and beyond setting (per iRECIST).

  Baseline through 6 months

Secondary Outcomes (3)

• Percent time to progression according to RECIST v1.1

  Baseline through 2 years

• Percent overall survival according to RECIST v1.1

  Baseline through 2 years

• Percent of patients with toxicity according to CTCAE v4.03

  Baseline through 2 years

Study Arms (1)

Cabozantinib + Nivolumab + Ipilimumab

EXPERIMENTAL

All recurrent carcinosarcomas

Drug: Cabozantinib; Drug: Ipilimumab; Drug: Nivolumab

Interventions

Cabozantinib DRUG

Treatment with oral Cabozantinib once daily

Also known as: tyrosine kinase inhibitor

Cabozantinib + Nivolumab + Ipilimumab

Ipilimumab DRUG

IV administration of Ipilimumab on 21 day cycles

Also known as: anti-CTLA-4

Cabozantinib + Nivolumab + Ipilimumab

Nivolumab DRUG

IV administration of Nivolumab on 21 day cycles, followed by Nivolumab maintenance on 28 day cycles

Also known as: anti-PD-1

Cabozantinib + Nivolumab + Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of carcinosarcoma (independent of organ of origin).
• Received at least one prior chemotherapy regimen for their cancer.
• Must have measurable or evaluable lesion defined by iRECIST.
• Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
• Karnofsky performance status greater than or equal to 70% or ECOG PS = 0\~2
• Age ≥ 18 years.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
• White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases.
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Serum albumin ≥ 2.8 g/dl.
• Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85

You may not qualify if:

• Prior treatment with cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
• Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
• Low-dose low molecular weight heparins (LMWH) are permitted.
• Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
• iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
• b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Interventions

cabozantinib; Tyrosine Kinase Inhibitors; Ipilimumab; Nivolumab; spartalizumab

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rebecca C Arend, MD, MSPH

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: November 4, 2019
• Study Start: February 1, 2021
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)