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

• ClinicalTrials.gov Identifier: NCT04230954
• Recruitment Status: Recruiting
• First Posted: January 18, 2020
• Last Update Posted: August 20, 2020
• Sponsor: University of South Alabama
• Collaborator: Exelixis
• Information provided by (Responsible Party): University of South Alabama

Tracking Information

• First Submitted Date: January 13, 2020
• First Posted Date: January 18, 2020
• Last Update Posted Date: August 20, 2020
• Actual Study Start Date: April 16, 2020
• Estimated Primary Completion Date: June 28, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2020)

Progression Free Survival [ Time Frame: Up to 24 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 17, 2020)

• Overall Response Rate [ Time Frame: Up to 24 months ]
  Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria).
• Overall Survival [ Time Frame: Up to 24 months ]
  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 [ Time Frame: Up to 6 Months ]
  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 [ Time Frame: Up to 6 Months ]
  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.

Original Secondary Outcome Measures (submitted: January 13, 2020)

• Overall Response Rate [ Time Frame: Up to 24 months ]
  Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria).
• Overall Survival [ Time Frame: Up to 24 months ]
  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
• Safety and Tolerability [ Time Frame: Up to 6 Months ]
  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 [ Time Frame: Up to 6 Months ]
  Quality of life as assessed by EORTC QLQ-CX24 [1] cervical cancer-specific quality of life questionnaire.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cervical Cancer
• Recurrent Cervical Cancer
• Metastatic Cervical Cancer
• Persistent Cervical Cancer

Intervention

• Drug: Cabozantinib 40 MG oral once a day
  Cabozantinib 40 mg oral once a day
  Other Name: Cabometyx
• Drug: Pembrolizumab 200 mg IV every 3 weeks
  Pembrolizumab 200 mg IV every 3 weeks
  Other Name: Keytruda

Study Arms

Experimental: Cabozantinib (XL 184) Plus Pembrolizumab

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

Interventions:

• Drug: Cabozantinib 40 MG oral once a day
• Drug: Pembrolizumab 200 mg IV every 3 weeks

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 13, 2020): 39
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 28, 2022
• Estimated Primary Completion Date: June 28, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wendy Blount, RN, MSN; 251-445-9834; wlblount@health.southalabama.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04230954
• Other Study ID Numbers: IST-67-MCI-1001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of South Alabama
• Study Sponsor: University of South Alabama
• Collaborators: Exelixis

Investigators

• Principal Investigator: Rodney P Rocconi, MD; University of South Alabama

• PRS Account: University of South Alabama
• Verification Date: August 2020