Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma

NCT03534804 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI104688
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open label, non-randomized phase 2 study of the combination of pembrolizumab and cabozantinib to assess overall response rate (ORR), progression free survival at 6 months (PFS6), and overall survival (OS) in patients with metastatic urothelial carcinoma (UC) ineligible for cisplatin.

Conditions

Metastatic Urothelial Carcinoma; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Count of Participants With Response Measured by RECIST 1.1

  To evaluate measurable disease overall response. Subjects were evaluated by CT scans at regular intervals for disease assessment by RECISTv1.1 criteria for the duration of treatment. Response Evaluation Criteria in Solid Tumors (RECIST) is a standard measure of how well cancer patients respond to treatment. Possible scores are CR (Complete Response; total disappearance of all target lesions), PR (Partial Response; at least a 30% decrease of the sum of the longest diameter of all target lesions), PD (Progressive Disease; at least a 20% increase of the sum of the longest diameter of all target lesions), and SD (Stable Disease; neither a sufficient decrease for PR, or sufficient increase for PD). Overall response is the count of PR and CR scores among the participants' best RECISTv1.1 responses.

  From baseline disease assessment to best response disease assessment, measured up to 28 months.

Secondary Outcomes (3)

• Count of Participants Who Were Progression-free at the Completion of Study Follow-up (PFS).

  Up to 34 months from the start of the study treatment.

• Count of Overall Survival (OS) at Completion of Study Follow-up

  Up to 34 months from the start of the study treatment.

• Occurrence of Adverse Events and Serious Adverse Events

  Up to 31 months from the start of study treatment.

Study Arms (1)

Cabozantinib and Pembrolizumab, all patients

EXPERIMENTAL

Drug: Cabozantinib; Drug: Pembrolizumab

Interventions

Cabozantinib DRUG

Cabozantinib is administered at 40 mg oral daily

Also known as: XL184

Cabozantinib and Pembrolizumab, all patients

Pembrolizumab DRUG

Pembrolizumab will be administered at a fixed dose of 200mg intravenously every 3 weeks.

Cabozantinib and Pembrolizumab, all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven transitional cell or urothelial carcinoma.
• Patients with locally advanced or metastatic urothelial carcinoma must meet one of the following:
• Patients who are not eligible for cisplatin-containing chemotherapy AND whose tumors express PD-L1 (Combined Positive Score (CPS) ≥ 10 as determined by an FDA-approved test; OR
• Patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
• Metastatic (any N+ or M1) or locally advanced, unresectable (T4bN0) disease.
• Measurable disease is required as determined by RECIST v1.1.
• Performance Status ECOG 0-2
• Cisplatin-ineligibility based on ≥1 of the following:
• Estimated creatinine clearance between ≥30 and \<60 ml/min (Cockcroft-Gault formula)
• ECOG PS\>1
• Hearing loss
• Baseline neuropathy \> grade 1.
• Patient refusal
• Be greater to or equal to 18 years of age on day of signing informed consent.
• Serum albumin ≥ 2.8 g/dl

You may not qualify if:

• Prior chemotherapy for metastatic urothelial carcinoma.
• Prior chemotherapy for localized urothelial carcinoma that has been completed less than 6 months before registration.
• Variant histologies other than urothelial carcinoma will not be allowed. Patients with a component of variant histologies will be allowed to enroll, if urothelial carcinoma is the predominant histology per investigator judgement. Patients with any component of small cell will be excluded.
• Has received prior treatment with cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other checkpoint inhibitors previously.
• Radiation therapy for bone metastasis ≤ 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Concomitant anticoagulation with oral anticoagulants except for those specified below.
• Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
• Low-dose low molecular weight heparins (LMWH) are permitted.
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban is allowed in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before the first dose of study treatment without, clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 × ULN within 14 days before the first dose of study treatment.

Sponsors & Collaborators

• University of Utah: lead
• Exelixis: collaborator

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

cabozantinib; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: IIT Data Management Team
• Organization: Research Compliance Office, Huntsman Cancer Institute

IITDataManagement@hci.utah.edu

801-213-6215

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label, non-randomized phase 2 study

Study Record Dates

• First Submitted: May 11, 2018
• First Posted: May 23, 2018
• Study Start: September 18, 2018
• Primary Completion: August 2, 2023
• Study Completion: April 15, 2024
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)