RECRUITING

Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma

Conditions

Gynecologic Cancer Carcinoma Uterine Cancer Endometrial Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase Ib/II Single Arm Study of Cabozantinib Plus Dostarlimab in Women with Recurrent Gynecologic Carcinosarcoma

Quick Facts

Study Start:2023-08-20

Study Completion:2026-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05559879

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Histologically confirmed diagnosis of carcinosarcoma (independent of organ of gynecologic origin) 2. Received at least one prior chemotherapy regimen for their cancer 3. Must have measurable or evaluable lesion defined by iRECIST 4. 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 5. ECOG Performance Status of 0-2 6. Age ≥ 18 years 7. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment: 1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support. 2. White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L). 3. Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion. 4. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 5. 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. 6. Total bilirubin ≤ 1.5 x ULN (for patients with Gilbert's disease ≤ 3 x ULN). 7. Serum albumin ≥ 2.8 g/dl. 8. Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation: 8. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document. 9. Women of childbearing potential (WOCBP) ie. sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment. 10. Females should not breastfeed while receiving treatment on trial. 11. Female patients of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had a prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression, or other reasons.	1. Prior treatment with cabozantinib. 2. 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. 3. Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment. 4. 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. 5. 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. 6. 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: 1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2. 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. 7. 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. 8. The patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: 9. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. 10. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment \[add reference for Fridericia formula\]. 11. Inability to swallow tablets. 12. Previously identified allergy or hypersensitivity to components of the study treatment formulations. 13. Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. 14. Patients with concurrent cytotoxic chemotherapy or radiation therapy are excluded. 15. Patients with a serious chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment. 16. Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded. 17. Presence of a known active acute or chronic infection including: a urinary tract infection, HIV or viral hepatitis; however, it is acceptable to treat an acute infection and then re-screen or re-evaluate eligibility. 18. Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment 19. Other clinically significant disorders: 1. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. 2. Active, known, or suspected autoimmune disease (exceptions: type 1 diabetes mellitus, hypothyroidism, skin disorders, conditions not expected to recur in the absence of an external trigger) 3. Malabsorption syndrome 4. Requirement for hemodialysis or peritoneal dialysis 5. History of solid organ or allogenic stem cell transplant

Inclusion Criteria

Exclusion Criteria

1. Histologically confirmed diagnosis of carcinosarcoma (independent of organ of gynecologic origin)
2. Received at least one prior chemotherapy regimen for their cancer
3. Must have measurable or evaluable lesion defined by iRECIST
4. 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
5. ECOG Performance Status of 0-2
6. Age ≥ 18 years
7. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
2. White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
3. Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion.
4. Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
5. 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.
6. Total bilirubin ≤ 1.5 x ULN (for patients with Gilbert's disease ≤ 3 x ULN).
7. Serum albumin ≥ 2.8 g/dl.
8. Serum creatinine ≤ 2.0 x ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation:
8. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
9. Women of childbearing potential (WOCBP) ie. sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment.
10. Females should not breastfeed while receiving treatment on trial.
11. Female patients of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had a prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression, or other reasons.

1. Prior treatment with cabozantinib.
2. 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.
3. Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
4. 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.
5. 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.
6. 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:
1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
2. 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.
7. 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.
8. The patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
9. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
10. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment \[add reference for Fridericia formula\].
11. Inability to swallow tablets.
12. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
13. Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy.
14. Patients with concurrent cytotoxic chemotherapy or radiation therapy are excluded.
15. Patients with a serious chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment.
16. Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
17. Presence of a known active acute or chronic infection including: a urinary tract infection, HIV or viral hepatitis; however, it is acceptable to treat an acute infection and then re-screen or re-evaluate eligibility.
18. Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment
19. Other clinically significant disorders:
1. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
2. Active, known, or suspected autoimmune disease (exceptions: type 1 diabetes mellitus, hypothyroidism, skin disorders, conditions not expected to recur in the absence of an external trigger)
3. Malabsorption syndrome
4. Requirement for hemodialysis or peritoneal dialysis
5. History of solid organ or allogenic stem cell transplant

Contacts and Locations

Study Contact

Rebecca Arend, MD, MSPH

CONTACT

2059344986

rarend@uabmc.edu

Pamela Hardwick, RN

CONTACT

205-975-5387

pamdixon@uab.edu

Study Locations (Sites)

O'Neal Comprehensive Cancer Center at UAB

Birmingham, Alabama, 35294

United States

Collaborators and Investigators

Sponsor: University of Alabama at Birmingham

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-20

Study Completion Date2026-01

Study Record Updates

Study Start Date2023-08-20

Study Completion Date2026-01

Terms related to this study

Keywords Provided by Researchers

Gynecologic Cancer
Carcinoma
Uterine Cancer
Endometrial Cancer

Additional Relevant MeSH Terms

Gynecologic Cancer
Carcinoma
Uterine Cancer
Endometrial Cancer