Study of CAbozantinib in Combination with AtezolizumaB for Muscle-Invasive BladdEr Cancer

NCT04289779 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU18-343
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label phase II study assessing the activity of cabozantinib combined with atezolizumab in patients with resectable muscle-invasive urothelial carcinoma who are ineligible for cisplatin-based therapy or decline cisplatin-based therapy. Each cycle equals 21 days. The dose of atezolizumab is 1200 mg IV flat dose every 3 weeks (Day 1) plus cabozantinib 40 mg orally daily (Day 1 through Day 21). Patients will receive three cycles of treatment prior to cystectomy unless they discontinue treatment for unacceptable toxicity or progressive disease by RECIST v1.1 or withdraw consent.

Conditions

Bladder Cancer

Keywords

muscle invasive

Outcome Measures

Primary Outcomes (1)

• Pathologic Response Rate

  Estimate the pathologic response (PaR) rate to neoadjuvant cabozantinib and atezolizumab in subjects with muscle-invasive urothelial cancer of the bladder. Pathologic response rate (PaR) is defined as the absence of residual muscle-invasive cancer in the surgical specimen (pathologic downstaging to ≤ pT1pN0), which includes pT0, pT1, pTa, and pTis

  12 months

Secondary Outcomes (3)

• Frequency and Severity of Adverse Events

  12 months

• Pathologic complete response rate

  12 months

• Event Free Survival

  24 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Cabozantinib 40 mg orally daily x 9 weeks plus Atezolizumab 1200 mg every 3 weeks x 3 doses

Drug: Cabozantinib; Drug: Atezolizumab; Procedure: Cystectomy

Interventions

Cabozantinib DRUG

Cabozantinib 40 mg orally daily for 3 cycles

Also known as: cabometyx

Treatment Arm

Atezolizumab DRUG

Atezolizumab 1200 mg IV every 3 weeks for 3 cycles

Also known as: Tecentriq

Treatment Arm

Cystectomy PROCEDURE

Patients will receive three cycles of treatment prior to cystectomy unless they discontinue treatment for unacceptable toxicity or progressive disease by RECIST v1.1 or withdraw consent.

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥18 years at the time of consent.
• ECOG Performance Status of ≤ 2 within 28 days prior to registration.
• Histological or cytologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle-invasion is allowed.
• Archival tissue is required, if available. The tissue should be identified at screening and shipped after registration, prior to Cycle 3 Day 1. If archival tissue is not available a repeat biopsy is not required, and the subject may still be eligible. Archival tissue should have been obtained within 60 days prior to registration.
• Urothelial carcinoma should be the predominant component (≥ 50%). NOTE: Any neuroendocrine differentiation is not permitted.
• Clinical stage T2-T4aN0/xM0 disease.
• No clinical or radiographic evidence for locally advanced or metastatic disease.
• Medically appropriate candidate for radical cystectomy as assessed by surgeon.
• Patients must have a contraindication to cisplatin or decline cisplatin based neoadjuvant chemotherapy. Absolute or relative contraindication to cisplatin, defined as one or more of the following within 28 days prior to registration (Grading per CTCAE v5):
• Creatinine clearance \< 60 mL/min (Cockcroft-Gault formula will be used to calculate creatinine clearance)
• Grade ≥ 2 hearing loss
• Grade ≥ 2 neuropathy
• No radiation therapy \< 4 weeks of registration. NOTE: prior radiation therapy to the bladder is not allowed.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatment.

You may not qualify if:

• Prior treatment with cabozantinib.
• Severe infection within 4 weeks prior to initiation of study treatment per investigator assessment. Examples include hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Active infection requiring systemic therapy.
• Active tuberculosis.
• Prior history of stem cell or solid organ transplantation.
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the study or within 5 months after the last dose of study drug.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Treatment with any investigational drug within 30 days prior to registration.
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or other cancer for which the subject has been disease-free for at least five years. Patients with localized prostate cancer who are either being followed by an active surveillance program OR planning to undergo definitive treatment are also eligible.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. NOTE: Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies are excluded. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded.
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab or cabozantinib formulation.
• Prior treatment with the following is prohibited unless otherwise specified:
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed).
• Any type of small molecule kinase inhibitor within 2 weeks before first dose of study treatment.

Sponsors & Collaborators

• Deepak Kilari: lead
• Exelixis: collaborator
• Genentech, Inc.: collaborator
• Medical College of Wisconsin: collaborator

Study Sites (6)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

cabozantinib; atezolizumab; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Deepak Kilari, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: February 28, 2020
• Study Start: May 21, 2020
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)