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BRIEF TITLE: Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors


  • Org Study ID: XL184-021
  • Secondary ID:
  • NCT ID: NCT03170960
  • NCT Alias:
  • Sponsor: Exelixis - Industry
  • Source: Exelixis

Brief Summary

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 multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric cancer/gastroesophageal junction cancer/lower esophageal cancer (GC/GEJC/LEC), colorectal cancer (CRC), head and neck (H&N) cancer, and differentiated thyroid cancer (DTC). 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. Three exploratory single-agent cabozantinib (SAC) cohorts may also be enrolled with UC, NSCLC, or CRPC subjects. One exploratory single-agent atezolizumab (SAA) cohort may also be enrolled with CRPC subjects. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.

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: to determine the preliminary efficacy (objective response rate [ORR]
per RECIST 1.1) and safety of the recommended combination dose of cabozantinib with
atezolizumab in eighteen tumor-specific cohorts including subjects with advanced UC,
RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N, and DTC.

- Exploratory SAC Cohorts: Descriptive efficacy, safety, PK, and biomarker analyses of
single-agent cabozantinib in UC, NSCLC, and CRPC subjects

- Exploratory SAA Cohort: Descriptive efficacy, safety, PK, and biomarker analyses of
single-agent atezolizumab in CRPC subjects

Overal Status Start Date Phase Study Type
Recruiting September 5, 2017 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Dose Escalation: MTD/Recommended Dose

Primary Outcome 1 - Time Frame: Up to 6 months

Primary Outcome 2 - Measure: Dose Expansion: ORR

Primary Outcome 2 - Time Frame: Up to 31 months

Condition:

  • Urothelial Carcinoma
  • Renal Cell Carcinoma
  • Non-Small Cell Lung Cancer
  • Castration-resistant Prostate Cancer
  • Triple Negative Breast Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Hepatocellular Carcinoma
  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma
  • Colorectal Cancer
  • Head and Neck Cancer
  • Differentiated Thyroid Cancer
  • Lower Esophageal Cancer

Eligibility

Criteria:
Inclusion Criteria:

1. Cytologically or histologically and radiologically confirmed solid tumor that is
inoperable, locally advanced, metastatic, or recurrent:

- Dose-Escalation Stage:

- Subjects with UC (including renal pelvis, ureter, bladder, urethra) after
prior platinum-based therapy, or

- Subjects with RCC (clear cell, non-clear cell histology) with or without
prior systemic anticancer therapy

- Expansion Stage:

- Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC,
TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N cancer, and DTC as outlined above)

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 except in Expansion Cohorts
5, 7, 9, 11, 17, 19 and 20. 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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Exelixis Clinical Trials

Phone: 1-888-EXELIXIS (888-393-5494)

Email: druginfo@exelixis.com

Locations

Facility Status Contact
Exelixis Clinical Site #53
Gilbert, Arizona 85234
United States
Recruiting
Exelixis Clinical Site #18
Phoenix, Arizona 85054
United States
Recruiting
Exelixis Clinical Site #1
Duarte, California 91010
United States
Recruiting
Exelixis Clinical Site #20
La Jolla, California 92090
United States
Recruiting
Exelixis Clinical Site #46
Los Angeles, California 90025
United States
Recruiting
Exelixis Clinical Site #51
Newport Beach, California 92663
United States
Recruiting
Exelixis Clinical Site #21
Stanford, California 94305
United States
Recruiting
Exelixis Clinical Site #34
Denver, Colorado 80218
United States
Recruiting
Exelixis Clinical Site #50
Denver, Colorado 80218
United States
Recruiting
Exelixis Clinical Site #42
New Haven, Connecticut 06511
United States
Recruiting
Exelixis Clinical Site #48
Washington, District of Columbia 20007
United States
Recruiting
Exelixis Clinical Site #16
Jacksonville, Florida 32224
United States
Recruiting
Exelixis Clinical Site #32
Harvey, Illinois 60426
United States
Recruiting
Exelixis Clinical Site #23
Fairway, Kansas 66205
United States
Recruiting
Exelixis Clinical Site #57
Lexington, Kentucky 40536
United States
Recruiting
Exelixis Clinical Site #24
New Orleans, Louisiana 70112
United States
Recruiting
Exelixis Clinical Site #10
Boston, Massachusetts 02215
United States
Recruiting
Exelixis Clinical Site #3
Detroit, Michigan 48201
United States
Recruiting
Exelixis Clinical Site #17
Rochester, Minnesota 55905
United States
Recruiting
Exelixis Clinical Site #43
Kansas City, Missouri 64111
United States
Recruiting
Exelixis Clinical Site #35
Omaha, Nebraska 68130
United States
Recruiting
Exelixis Clinical Site #38
Camden, New Jersey 08103
United States
Recruiting
Exelixis Clinical Site #27
East Brunswick, New Jersey 08816
United States
Recruiting
Exelixis Clinical Site #31
New Brunswick, New Jersey 08903
United States
Recruiting
Exelixis Clinical Site #37
Bronx, New York 10461
United States
Recruiting
Exelixis Clinical Site #40
East Setauket, New York 11733
United States
Recruiting
Exelixis Clinical Site #11
New York, New York 10029
United States
Recruiting
Exelixis Clinical Site #49
Columbus, Ohio 43210
United States
Recruiting
Exelixis Clinical Site #6
Oklahoma City, Oklahoma 73120
United States
Recruiting
Exelixis Clinical Site #45
Portland, Oregon 97239
United States
Recruiting
Exelixis Clinical Site #41
Bethlehem, Pennsylvania 18015
United States
Recruiting
Exelixis Clinical Site #15
Philadelphia, Pennsylvania 19107
United States
Recruiting
Exelixis Clinical Site #55
Philadelphia, Pennsylvania 19111
United States
Recruiting
Exelixis Clinical Site #13
Dallas, Texas 75246
United States
Recruiting
Exelixis Clinical Site #26
Dallas, Texas 75390
United States
Recruiting
Exelixis Clinical Site #29
Houston, Texas 77030
United States
Recruiting
Exelixis Clinical Site #39
Houston, Texas 77030
United States
Recruiting
Exelixis Clinical Site #44
Houston, Texas 77030
United States
Recruiting
Exelixis Clinical Site #33
Lubbock, Texas 79410
United States
Recruiting
Exelixis Clinical Site #2
Salt Lake City, Utah 84112
United States
Recruiting
Exelixis Clinical Site #30
Blacksburg, Virginia 24060
United States
Recruiting
Exelixis Clinical Site #14
Charlottesville, Virginia 22908
United States
Recruiting
Exelixis Clinical Site #52
Gent, 9000
Belgium
Recruiting
Exelixis Clinical Site #54
Leuven, 3000
Belgium
Recruiting
Exelixis Clinical Site #8
Villejuif, Cedex 94805
France
Recruiting
Exelixis Clinical Site #7
Paris, 75010
France
Recruiting
Exelixis Clinical Site #56
Düsseldorf, Nordrhein-Westfalen 40225
Germany
Recruiting
Exelixis Clinical Site #36
Tübingen, 72076
Germany
Recruiting
Exelixis Clinical Site #47
Rozzano, Milano 20089
Italy
Recruiting
Exelixis Clinical Site #25
Milano, 20133
Italy
Recruiting
Exelixis Clinical Site #4
Milano, 20133
Italy
Recruiting
Exelixis Clinical Site #12
Nijmegen, Gelderland 6525 GA
Netherlands
Recruiting
Exelixis Clinical Site #28
Barcelona, 08035
Spain
Recruiting
Exelixis Clinical Site #9
Barcelona, 08035
Spain
Recruiting
Exelixis Clinical Site #22
Madrid, 28041
Spain
Recruiting
Exelixis Clinical Site #5
Madrid, 28041
Spain
Recruiting
Exelixis Clinical Site #19
London, EC1M 6BQ
United Kingdom
Recruiting