A Phase 2 Study of CAbozantinib in Combination with AtezolizumaB As NeoAdjuvant Treatment for Muscle-Invasive BladdEr Cancer
Overview
- Phase
- Phase 2
- Intervention
- Cabozantinib
- Conditions
- Bladder Cancer
- Sponsor
- Deepak Kilari
- Enrollment
- 46
- Locations
- 6
- Primary Endpoint
- Pathologic Response Rate
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
Deepak Kilari
Sponsor-Investigator
Hoosier Cancer Research Network
Eligibility Criteria
Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Treatment Arm
Cabozantinib 40 mg orally daily x 9 weeks plus Atezolizumab 1200 mg every 3 weeks x 3 doses
Intervention: Cabozantinib
Treatment Arm
Cabozantinib 40 mg orally daily x 9 weeks plus Atezolizumab 1200 mg every 3 weeks x 3 doses
Intervention: Atezolizumab
Treatment Arm
Cabozantinib 40 mg orally daily x 9 weeks plus Atezolizumab 1200 mg every 3 weeks x 3 doses
Intervention: Cystectomy
Outcomes
Primary Outcomes
Pathologic Response Rate
Time Frame: 12 months
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
Secondary Outcomes
- Event Free Survival(24 months)
- Frequency and Severity of Adverse Events(12 months)
- Pathologic complete response rate(12 months)