Gynecologic CancerPhase 1/2NCT05559879
Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma
A Phase 1/2 study testing Cabo + Dostarlimab in people with Gynecologic Cancer and Carcinoma, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Gynecologic Cancer, Carcinoma, Uterine Cancer
- What is being tested?
- Cabo + Dostarlimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2023to Apr 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- [(140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85 i. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol).
- Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
- 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.
- Females should not breastfeed while receiving treatment on trial.
- 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.
Who cannot join
- 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:
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- 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:
- Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
- Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
- 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.
- 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.
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
- Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose.
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
- Lesions invading or encasing any major blood vessels. f. Other clinically significant disorders that would preclude safe study participation.
- Serious non-healing wound/ulcer/bone fracture ii. Uncompensated/symptomatic hypothyroidism (i.e. inadequately treated hypothyroidism) iii. Moderate to severe hepatic impairment (Child-Pugh B or C)
- 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.
- 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].
- Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
- Inability to swallow tablets.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- 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.
- Patients with concurrent cytotoxic chemotherapy or radiation therapy are excluded.
- 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.
- Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
- 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.
- Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment
- Other clinically significant disorders:
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- 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)
- Malabsorption syndrome
- Requirement for hemodialysis or peritoneal dialysis
- History of solid organ or allogenic stem cell transplant
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Margaret A Thomas, MPH contact
United States1 site, 1 recruiting
- Recruiting
O'Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama, 35294
Margaret Thomas, MPH, margaretathomas@uabmc.edu
Michael Toboni, MD
About this study
Official title: A Phase Ib/II Single Arm Study of Cabozantinib Plus Dostarlimab in Women With Recurrent Gynecologic Carcinosarcoma
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
- Being tested
- Cabo + Dostarlimab
- Keywords
- Gynecologic Cancer, Carcinoma, Uterine Cancer, Endometrial Cancer
- Medical subject headings
- Carcinoma, Uterine Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabo + DostarlimabDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Cabo + Dostarlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2022
- Study start20 Aug 2023
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gynecologic CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Toboni, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05559879
- Sponsor's protocol ID
- IRB-300008749 (UAB21111)
- Other IDs
- 000547299
- Status last verified
- Apr 2026
- First submitted
- 29 Aug 2022
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Single Arm Study of Cabozantinib Plus Dostarlimab in Women With Recurrent Gynecologic Carcinosarcoma
- ClinicalTrials.gov ID
- NCT05559879
- Acronym / sponsor ID
- IRB-300008749 (UAB21111)
- Conditions
- Gynecologic Cancer, Carcinoma, Uterine Cancer, Endometrial Cancer
- Keywords
- Gynecologic Cancer, Carcinoma, Uterine Cancer, Endometrial Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 20 Aug 2023 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 29 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cabo + Dostarlimab | Experimental | Drug: Cabo + DostarlimabCabozantinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (37 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cabo + DostarlimabCombination 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 | Drug | Cabo + Dostarlimab |
Primary outcome
Progression-Free Survival at 6 months
Time frame: 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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Margaret A Thomas, MPH contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cabo + Dostarlimab in people with Gynecologic Cancer and Carcinoma, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Toboni, MD, MSPH ((205) 934-4793, mdtoboni@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.