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

Primary Purpose

Cervical Cancer, Recurrent Cervical Cancer, Metastatic Cervical Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cabozantinib 40 MG oral once a day
Pembrolizumab 200 mg IV every 3 weeks
Sponsored by
University of South Alabama
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring Recurrent Cervical Cancer, Cervical Cancer, Cervical Carcinoma, PD L1 positivity, Immunotherapy, Squamous Carcinoma, Adenocarcinoma, Adenosquamous Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of South Alabama Mitchell Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cabozantinib (XL 184) Plus Pembrolizumab

Arm Description

A Phase II Study of Cabozantinib (XL 184)Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Response Rate
Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria).
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
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
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.

Full Information

First Posted
January 13, 2020
Last Updated
June 3, 2022
Sponsor
University of South Alabama
Collaborators
Exelixis
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1. Study Identification

Unique Protocol Identification Number
NCT04230954
Brief Title
Cabozantinib Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer
Official Title
A Phase II Study of Cabozantinib (XL184) Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Terminated
Why Stopped
PI left institution
Study Start Date
April 16, 2020 (Actual)
Primary Completion Date
February 16, 2022 (Actual)
Study Completion Date
February 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of South Alabama
Collaborators
Exelixis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Drug: Cabozantinib Drug: Pembrolizumab
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Recurrent Cervical Cancer, Metastatic Cervical Cancer, Persistent Cervical Cancer
Keywords
Recurrent Cervical Cancer, Cervical Cancer, Cervical Carcinoma, PD L1 positivity, Immunotherapy, Squamous Carcinoma, Adenocarcinoma, Adenosquamous Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cabozantinib (XL 184) Plus Pembrolizumab
Arm Type
Experimental
Arm Description
A Phase II Study of Cabozantinib (XL 184)Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer
Intervention Type
Drug
Intervention Name(s)
Cabozantinib 40 MG oral once a day
Other Intervention Name(s)
Cabometyx
Intervention Description
Cabozantinib 40 mg oral once a day
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab 200 mg IV every 3 weeks
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab 200 mg IV every 3 weeks
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria).
Time Frame
Up to 24 months
Title
Overall Survival
Description
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
Time Frame
Up to 24 months
Title
Incidence of Emergent Adverse Events
Description
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
Time Frame
Up to 6 Months
Title
Cervical Cancer Quality of Life
Description
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.
Time Frame
Up to 6 Months

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefanie White
Organizational Affiliation
University of South Alabama
Official's Role
Study Director
Facility Information:
Facility Name
University of South Alabama Mitchell Cancer Institute
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19825956
Citation
Karim R, Jordanova ES, Piersma SJ, Kenter GG, Chen L, Boer JM, Melief CJ, van der Burg SH. Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. Clin Cancer Res. 2009 Oct 15;15(20):6341-7. doi: 10.1158/1078-0432.CCR-09-1652. Epub 2009 Oct 13.
Results Reference
background
PubMed Identifier
23521696
Citation
Yang W, Song Y, Lu YL, Sun JZ, Wang HW. Increased expression of programmed death (PD)-1 and its ligand PD-L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia. Immunology. 2013 Aug;139(4):513-22. doi: 10.1111/imm.12101.
Results Reference
background
PubMed Identifier
21926191
Citation
Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16.
Results Reference
background
PubMed Identifier
30943124
Citation
Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3.
Results Reference
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Cabozantinib Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

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