Cabozantinib Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

Study Overview
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Brief Summary
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Drug: Cabozantinib Drug: Pembrolizumab

Detailed Description
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This study is a multi-center, single arm, open label trial to evaluate the efficacy and safety of Cabozantinib (XL184) plus Pembrolizumab in recurrent, persistent and/or metastatic cervical cancer with PD-L1 tumor positivity.

Official Title
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A Phase II Study of Cabozantinib (XL184) Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

Conditions
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Cervical Cancer, Recurrent Cervical Cancer, Metastatic Cervical Cancer, Persistent Cervical Cancer

Intervention / Treatment
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* Drug: Cabozantinib 40 MG oral once a day
* Drug: Pembrolizumab 200 mg IV every 3 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent or persistent cervical cancer after prior systemic chemotherapy for which there is no curative intent option Documented histologic cervical cancer (acceptable histologies: squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma) Patients must have PD-L1 tumor positivity as defined as CPS>/= 1 Age greater than 18 and ECOG performance status of <= 2 Adequate organ and marrow function Exclusion Criteria: Prior treatment with cabozantinib or pembrolizumab Receipt of any type of small molecule kinase inhibitor Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery Anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel) Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: Cardiovascular disorders: Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias Uncontrolled hypertension despite optimal antihypertensive treatment, stroke Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose Active autoimmune disease requiring systemic therapy within the past 2 years Active infection requiring systemic therapy within the past month History of immunodeficiency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib (XL 184) Plus Pembrolizumab<br>A Phase II Study of Cabozantinib (XL 184)Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer | Drug: Cabozantinib 40 MG oral once a day<br>* Cabozantinib 40 mg oral once a day<br>* Other names: Cabometyx;Drug: Pembrolizumab 200 mg IV every 3 weeks<br>* Pembrolizumab 200 mg IV every 3 weeks<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Six months progression free survival as defined by RECIST v1.1 measured from signed written consent to the date of first documented tumor progression using RECIST v1.1, or death due to any cause or 24 months after the end of study treatment. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria). | Up to 24 months | 
| Overall Survival | Overall survival will be defined as the time from signed written consent to the date of death or 24 months after the end of study treatment. A patient who has not died will be censored at the last known date of contact | Up to 24 months | 
| Incidence of Emergent Adverse Events | Evaluate the safety and tolerability measured by incidence of adverse events and serious adverse events, deaths, and laboratory abnormalities as measured by Common Terminology Criteria for Adverse Events v.4.0 | Up to 6 Months | 
| Cervical Cancer Quality of Life | Quality of life as assessed by FACT Cx quality of life questionnaire. This frequency questionnaire is scaled from 0-4 with 0 being not at all and 4 being very much. | Up to 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Cervical Cancer, Cervical Cancer, Cervical Carcinoma, PD L1 positivity, Immunotherapy, Squamous Carcinoma, Adenocarcinoma, Adenosquamous Carcinoma