A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
Condition: Urothelial Carcinoma, Renal Cell Carcinoma
- Drug: cabozantinib
- Drug: atezolizumab
- Drug: cabozantinib
Purpose: This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in subjects with advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra) or renal cell carcinoma (RCC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination with standard dosing regimen of atezolizumab will be established. In the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy of the combination treatment in these tumor indications.
Study Type: Interventional
Clinical Trials Identifier NCT 8-digits: NCT03170960
Primary Outcome Measures:
- Measure: Dose Escalation: MTD/Recommended Dose
- Time Frame: Up to 6 months
- Safety Issue:
- Measure: Dose Expansion: ORR
- Time Frame: Up to 26 months
- Safety Issue:
Secondary Outcome Measures:
- Measure: Incidence and severity of nonserious AEs and SAEs (Safety)
- Time Frame: Up to 36 months
- Safety Issue:
Estimated Enrollment: 156
Study Start Date: September 5, 2017
Phase: Phase 1/Phase 2
- Age: minimum 18 Years maximum N/A
- Gender: All
- 1. Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:
- Dose-Escalation Stage:
- a. Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
- b. Subjects with RCC (clear cell, non-clear cell) with or without prior systemic anticancer therapy
- Expansion Stage:
- c. Expansion Cohort 1: Subjects with RCC with clear cell histology who have not received prior systemic anticancer therapy
- d. Expansion Cohort 2: Subjects with UC (including renal pelvis, ureter, bladder, urethra) who have progressed on or after platinum-containing chemotherapy
- e. Expansion Cohort 3: Subjects with UC (including bladder, renal pelvis, ureter, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced, or metastatic disease [Ineligible for cisplatin-based chemotherapy is defined by meeting one of the following criteria: impaired renal function (glomerular filtration rate [GFR] > 30 mL/min/1.73 m2 and < 60 mL/min/1.73 m2), hearing loss of ≥ 25 dB at two contiguous frequencies, or ≥ Grade 2 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v4.]
- f. Expansion Cohort 4: Subjects with UC (including bladder, renal pelvis, ureter, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced, or metastatic disease 2. Measurable disease per RECIST 1.1 as determined by the investigator. 3. Tumor tissue material available (archival or recent tumor biopsy) 4. Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. 5. Age eighteen years or older on the day of consent. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 7. Adequate organ and marrow function. 8. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception. 9. Female subjects of childbearing potential must not be pregnant at screening.
- Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy. Other restrictions regarding prior therapy may apply.
- Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment.
- Concomitant anticoagulation with oral anticoagulants.
- Subject is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
- The subject has uncontrolled, significant intercurrent or recent illness, including, but not limited to, an active or history of autoimmune disease or immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C).
- Pregnant or lactating females.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Diagnosis of another malignancy within 2 years before first dose of study treatment.
- Exelixis Clinical Trials
- 1-888-EXELIXIS (888-393-5494)
- Exelixis Clinical Site #1
- Duarte California 91010 United States
- Exelixis Clinical Site #2
- Salt Lake City Utah 84112 United States
View trial on ClinicalTrials.gov