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

Cervical Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04230954
• Other study ID #: IST-67-MCI-1001
• Status: Terminated
• Phase: Phase 2
• Start date: April 16, 2020
• Est. completion date: February 16, 2022

Study information

• Verified date: June 2022
• Source: University of South Alabama
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Drug: Cabozantinib Drug: Pembrolizumab

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: February 16, 2022
• Est. primary completion date: February 16, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Metastatic Cervical Cancer
• Persistent Cervical Cancer
• Recurrent Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of South Alabama	Exelixis

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response Rate	Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria).	Up to 24 months
Secondary	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
Secondary	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
Secondary	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