Clinical trial NCT04230954: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: University of South Alabama
Sponsor class: OTHER
Collaborators: name: Exelixis
First posted: 2020-01-18
Enrollment: 5
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Up to 24 months
measure: Overall Survival
timeFrame: Up to 24 months
measure: Incidence of Emergent Adverse Events
timeFrame: Up to 6 Months
measure: Cervical Cancer Quality of Life
timeFrame: Up to 6 Months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
Study officials:
affiliation: University of South Alabama
name: Stefanie White
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.