Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma

NCT05559879 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-300008749 (UAB21111)000547299
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Immunotherapy has gained a significant amount of attention recently, but its efficacy as a single agent in gynecological cancers has been disappointing. Pre-clinical evidence supports the combination of using Vascular Endothelial Growth Factors (VEGF) inhibitors with immunotherapy. VEGF inhibitors suppress the activation of tumor-associated macrophages (TAMs) and VEGF has been shown to affect the functional maturation of dendritic cells; therefore, VEGF inhibitors could improve the function of antigen presentation. In this study, Cabozantinib (VEGF inhibitor) and Dostarlimab (immunotherapeutic drug) will be admnistered as a combination to patients with recurrent gynecologic carcinosarcoma.

Conditions

Gynecologic Cancer; Carcinoma; Uterine Cancer; Endometrial Cancer

Keywords

Gynecologic Cancer; Carcinoma; Uterine Cancer; Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival at 6 months

  To estimate the proportion of patients with recurrent carcinosarcoma-who survive progression-free for at least 6 months from the start of treatment-treated with cabozantinib + dostarlimab in the second line setting and beyond (per imaging Response Evaluation Criteria in Solid Tumours).

  6 months

Study Arms (1)

Cabo + Dostarlimab

EXPERIMENTAL

Cabozantinib 40 mg by mouth every day + Dostarlimab 500 mg intravenous every 3 weeks followed by maintenance therapy: Cabozantinib 40 mg by mouth every day + Dostarlimab 1000 mg intravenous every 6 weeks

Drug: Cabo + Dostarlimab

Interventions

Cabo + Dostarlimab DRUG

Combination of standard dose of cabozantinib and 500 mg dostarlimab for first 4 cycles followed by standard dose of cabozantinib and 1000 mg of dostarlimab until 2 years of treatment

Cabo + Dostarlimab

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 gynecologic 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 v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• ECOG Performance Status of 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 patients 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:

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 or 5 half-lives (whichever is longer) 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. Patients 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 patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixabin, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The patient 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 patient 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) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., 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 patient has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., 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.
• ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

O'Neal Comprehensive Cancer Center at UAB

Birmingham, Alabama, 35294, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma; Uterine Neoplasms; Endometrial Neoplasms

Interventions

VMBP protocol; dostarlimab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Michael Toboni, MD, MSPH

CONTACT

(205) 934-4793; mdtoboni@uabmc.edu

Margaret A Thomas, MPH

CONTACT

margaretathomas@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a phase Ib/II, single-arm, combination therapy of the safety and efficacy of therapy involving a tyrosine kinase inhibitor along with immunotherapy in the setting of recurrent carcinosarcoma.

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: September 29, 2022
• Study Start: August 20, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)