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Trial record 1 of 1 for:    cabozantinib and atezolizumab
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Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified May 2017 by Exelixis
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT03170960
First received: May 23, 2017
Last updated: May 30, 2017
Last verified: May 2017
  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.

Condition Intervention Phase
Urothelial Carcinoma Renal Cell Carcinoma Drug: cabozantinib Drug: atezolizumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose Escalation followed by Dose Expansion
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Dose Escalation: MTD/Recommended Dose [ Time Frame: Up to 6 months ]
    To determine the maximum tolerated dose (MTD) and/or recommended dose and schedule for the subsequent Expansion Stage of daily oral administration of cabozantinib in subjects with solid tumors when taken in combination with atezolizumab.

  • Dose Expansion: ORR [ Time Frame: Up to 26 months ]
    To evaluate preliminary efficacy by estimating the Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1.


Secondary Outcome Measures:
  • Incidence and severity of nonserious AEs and SAEs (Safety) [ Time Frame: Up to 36 months ]
    To assess safety for the combination therapy through the evaluation of incidence and severity of nonserious adverse events (AEs) and serious adverse events (SAEs), including immune-related adverse events (irAEs).


Estimated Enrollment: 156
Anticipated Study Start Date: June 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation
Subjects will accrue in cohorts of 3-6 subjects for evaluation of cabozantinib tablet dose of either 20 mg, 40 mg, and 60 mg orally qd in combination with standard dosing regimen of atezolizumab (1200 mg infusion q3w). A standard "3 plus 3" design will be utilized to determine a recommended combination dosing regimen for the Expansion Stage.
Drug: cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at dose levels of 20 mg, 40 mg, or 60 mg.
Other Names:
  • Cabometyx
  • XL184
Drug: atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
Other Name: Tecentriq
Experimental: Expansion Cohort 1
Subjects with advanced RCC with clear cell histology who have not received prior systemic anticancer therapy.
Drug: atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
Other Name: Tecentriq
Drug: cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at the CRC-determined recommended dose from the Dose Escalation Stage
Other Names:
  • Cabometyx
  • XL184
Experimental: Expansion Cohort 2
Subjects with UC (including bladder, renal pelvis, ureter, urethra) who have progressed on or after platinum-containing chemotherapy.
Drug: atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
Other Name: Tecentriq
Drug: cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at the CRC-determined recommended dose from the Dose Escalation Stage
Other Names:
  • Cabometyx
  • XL184
Experimental: 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.
Drug: atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
Other Name: Tecentriq
Drug: cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at the CRC-determined recommended dose from the Dose Escalation Stage
Other Names:
  • Cabometyx
  • XL184
Experimental: 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.
Drug: atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
Other Name: Tecentriq
Drug: cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at the CRC-determined recommended dose from the Dose Escalation Stage
Other Names:
  • Cabometyx
  • XL184

Detailed Description:
  • Dose Escalation Stage: to determine the schedule and maximum tolerated dose (MTD) and/or recommended Expansion Stage dose of cabozantinib when taken in combination with a standard dosing regimen of atezolizumab (1200 mg infusion, once every 3 weeks).
  • Expansion Stage. Four expansion cohorts with a total of up to 120 subjects with advanced UC or RCC (up to 30 subjects in each cohort) may be enrolled to obtain additional efficacy safety, PK, and pharmacodynamic data at the recommended dose and schedule.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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.

Exclusion Criteria:

  1. 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.
  2. Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment.
  3. Concomitant anticoagulation with oral anticoagulants.
  4. Subject is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
  5. Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
  6. 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).
  7. Pregnant or lactating females.
  8. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  9. Diagnosis of another malignancy within 2 years before first dose of study treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03170960

Contacts
Contact: Exelixis Clinical Trials 1-888-EXELIXIS (888-393-5494) druginfo@exelixis.com
Contact: Backup or International 650-837-7400

Sponsors and Collaborators
Exelixis
  More Information

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT03170960     History of Changes
Other Study ID Numbers: XL184-021
Study First Received: May 23, 2017
Last Updated: May 30, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Exelixis:
Kidney
Bladder
Renal pelvis
Ureter
Urethra
Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2017