Clinical Trial - NCT03170960

Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Recruiting

Sponsor: Exelixis

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03170960

Protocol Info

Short Description: Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
Long Description: A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors
MGH Status: Open
Sponsor: Exelixis
Disease Program: GU

Next Steps


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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 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. Subjects enrolled in the SAC cohorts and SAA cohort may receive combination treatment with both cabozantinib and atezolizumab after they experience radiographic progressive disease per the Investigator per RECIST 1.1. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.
Condition Title Intervention Phase
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 cabozantinib atezolizumab cabozantinib cabozantinib Phase 1/Phase 2
Study Type Interventional
Official Title 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

Primary Outcome Measures

Dose Escalation: MTD/Recommended Dose [Time Frame: Up to 6 months] [Designated as safety issue: ]

Dose Expansion: ORR [Time Frame: Up to 31 months] [Designated as safety issue: ]


Secondary Outcome Measures

Incidence and severity of nonserious AEs and SAEs (Safety) [Time Frame: Up to 41 months] [Designated as safety issue: ]

Estimated Enrollment: 1732
Study Start Date: September 2017
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2020
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:atezolizumab
Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).

Experimental:Expansion Cohort 1

RCC subjects with clear cell histology who have not received prior systemic anticancer therapy.
Drug:cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at the Cohort Review Committee-determined recommended dose from the Dose Escalation Stage

Experimental:Expansion Cohort 2

UC subjects (including bladder, renal pelvis, ureter, urethra) who have progressed on or after platinum-containing chemotherapy.

Experimental:Expansion Cohort 3

UC subjects (including bladder, renal pelvis, ureter, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy.

Experimental:Expansion Cohort 4

UC subjects (including bladder, renal pelvis, ureter, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy.

Experimental:Expansion Cohort 5

UC subjects (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (ICI) (anti-PD1 or anti-PD-L1) therapy.

Experimental:Expansion Cohort 6

CRPC subjects who have radiographically progressed in soft tissue on or after enzalutamide and/or abiraterone acetate for metastatic disease.

Experimental:Expansion Cohort 7

Stage IV non-squamous NSCLC subjects who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (ICI) (anti-PD-1 or anti-PD-L1) therapy.

Experimental:Expansion Cohort 8

Stage IV non-squamous NSCLC subjects with positive PD-L1 expression and without prior systemic anticancer therapy.

Experimental:Expansion Cohort 9

Stage IV nonsquamous NSCLC subjects with sensitizing EGFR mutation who have radiographically progressed during or following prior treatment with an EGFR-targeting TKI. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy.

Experimental:Expansion Cohort 10

RCC subjects with non-clear cell histology who have had up to one prior VEGFR-targeting TKI therapy.

Experimental:Expansion Cohort 11

TNBC subjects who have radiographically progressed during or following treatment with at least one prior systemic anticancer therapy. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy.

Experimental:Expansion Cohort 12

OC subjects (including primary peritoneal cancer and fallopian tube cancer) who have platinum-resistant or refractory disease who have had up to two lines of prior systemic anticancer therapy.

Experimental:Expansion Cohort 13

EC subjects (serous or endometrioid histology) who have radiographically progressed during or following treatment with at least one prior systemic anticancer therapy.

Experimental:Expansion Cohort 14

HCC subjects (Child-Pugh score A) who have not received prior systemic anticancer therapy.

Experimental:Expansion Cohort 15

GC/GEJC/LEC subjects who have radiographically progressed during or following platinum-containing or fluoropyrimidine-containing chemotherapy.

Experimental:Expansion Cohort 16

CRC subjects who have radiographically progressed during or following systemic chemotherapy that contained fluoropyrimidine in combination with oxaliplatin or irinotecan.

Experimental:Expansion Cohort 17

H&N cancer subjects who have radiographically progressed during or following prior platinum-containing chemotherapy. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy.

Experimental:Expansion Cohort 18

DTC subjects (follicular, papillary, and poorly differentiated histologies) who are radioactive iodine (RAI) refractory or deemed ineligible for treatment with RAI.

Experimental:Expansion Cohort 19 (SAC)

UC subjects (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior ICI (anti-PD-1 or anti-PD-L1). Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.
Drug:cabozantinib
Supplied as 60-mg and 20-mg tablets; administered orally daily at 60 mg qd

Experimental:Expansion Cohort 20 (SAC)

Stage IV non-squamous NSCLC subjects who have radiographically progressed on or after treatment with one prior ICI (anti-PD-1 or anti-PD-L1). Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.

Experimental:Expansion Cohort 21 (SAC)

Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC. Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.

Experimental:Expansion Cohort 22 (SAA)

Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC. Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.

Experimental:Expansion Cohort 23

Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC

Experimental:Expansion Cohort 24

Metastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with at least one NHT and have received docetaxel for mCRPC

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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 (>10 mg daily prednisone equivalent) 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

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

Locations

  • United States, Arizona
    • Exelixis Clinical Site #53 Gilbert, Arizona, United States, 85234
    • Exelixis Clinical Site #18 Phoenix, Arizona, United States, 85054
  • United States, California
    • Exelixis Clinical Site #1 Duarte, California, United States, 91010
    • Exelixis Clinical Site #20 La Jolla, California, United States, 92090
    • Exelixis Clinical Site #46 Los Angeles, California, United States, 90025
    • Exelixis Clinical Site #51 Newport Beach, California, United States, 92663
    • Exelixis Clinical Site #62 Santa Monica, California, United States, 90404
    • Exelixis Clinical Site #21 Stanford, California, United States, 94305
  • United States, Colorado
    • Exelixis Clinical Site #34 Denver, Colorado, United States, 80218
    • Exelixis Clinical Site #50 Denver, Colorado, United States, 80218
  • United States, Connecticut
    • Exelixis Clinical Site #42 New Haven, Connecticut, United States, 06511
  • United States, District of Columbia
    • Exelixis Clinical Site #48 Washington, District of Columbia, United States, 20007
  • United States, Florida
    • Exelixis Clinical Site #16 Jacksonville, Florida, United States, 32224
    • Exelixis Clinical Site #76 Tampa, Florida, United States, 33612
  • United States, Georgia
    • Exelixis Clinical Site #60 Atlanta, Georgia, United States, 30318
  • United States, Illinois
    • Exelixis Clinical Site #32 Harvey, Illinois, United States, 60426
  • United States, Kansas
    • Exelixis Clinical Site #23 Fairway, Kansas, United States, 66205
  • United States, Kentucky
    • Exelixis Clinical Site #57 Lexington, Kentucky, United States, 40536
  • United States, Louisiana
    • Exelixis Clinical Site #24 New Orleans, Louisiana, United States, 70112
  • United States, Massachusetts
    • Exelixis Clinical Site #10 Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • Exelixis Clinical Site #3 Detroit, Michigan, United States, 48201
  • United States, Minnesota
    • Exelixis Clinical Site #17 Rochester, Minnesota, United States, 55905
  • United States, Missouri
    • Exelixis Clinical Site #65 Bolivar, Missouri, United States, 65613
    • Exelixis Clinical Site #43 Kansas City, Missouri, United States, 64111
  • United States, Nebraska
    • Exelixis Clinical Site #35 Omaha, Nebraska, United States, 68130
    • Exelixis Clinical Site #59 Omaha, Nebraska, United States, 68130
  • United States, Nevada
    • Exelixis Clinical Site #61 Las Vegas, Nevada, United States, 89169
  • United States, New Jersey
    • Exelixis Clinical Site #38 Camden, New Jersey, United States, 08103
    • Exelixis Clinical Site #27 East Brunswick, New Jersey, United States, 08816
    • Exelixis Clinical Site #31 New Brunswick, New Jersey, United States, 08903
  • United States, New York
    • Exelixis Clinical Site #37 Bronx, New York, United States, 10461
    • Exelixis Clinical Site #40 East Setauket, New York, United States, 11733
    • Exelixis Clinical Site #11 New York, New York, United States, 10029
  • United States, Ohio
    • Exelixis Clinical Site #67 Cleveland, Ohio, United States, 44195
    • Exelixis Clinical Site #49 Columbus, Ohio, United States, 43210
    • Exelixis Clinical Site #64 Kettering, Ohio, United States, 45409
  • United States, Oklahoma
    • Exelixis Clinical Site #71 Oklahoma City, Oklahoma, United States, 73104
    • Exelixis Clinical Site #6 Oklahoma City, Oklahoma, United States, 73120
  • United States, Oregon
    • Exelixis Clinical Site #45 Portland, Oregon, United States, 97239
  • United States, Pennsylvania
    • Exelixis Clinical Site #41 Bethlehem, Pennsylvania, United States, 18015
    • Exelixis Clinical Site #15 Philadelphia, Pennsylvania, United States, 19107
    • Exelixis Clinical Site #55 Philadelphia, Pennsylvania, United States, 19111
    • Exelixis Clinical Site #66 Pittsburgh, Pennsylvania, United States, 15232
  • United States, Texas
    • Exelixis Clinical Site #13 Dallas, Texas, United States, 75246
    • Exelixis Clinical Site #26 Dallas, Texas, United States, 75390
    • Exelixis Clinical Site #29 Houston, Texas, United States, 77030
    • Exelixis Clinical Site #39 Houston, Texas, United States, 77030
    • Exelixis Clinical Site #44 Houston, Texas, United States, 77030
    • Exelixis Clinical Site #33 Lubbock, Texas, United States, 79410
    • Exelixis Clinical Site #63 San Antonio, Texas, United States, 78229
  • United States, Utah
    • Exelixis Clinical Site #2 Salt Lake City, Utah, United States, 84112
  • United States, Virginia
    • Exelixis Clinical Site #30 Blacksburg, Virginia, United States, 24060
    • Exelixis Clinical Site #14 Charlottesville, Virginia, United States, 22908
  • Belgium,
    • Exelixis Clinical Site #52 Gent, , Belgium, 9000
    • Exelixis Clinical Site #54 Leuven, , Belgium, 3000
  • France, Cedex
    • Exelixis Clinical Site #8 Villejuif, Cedex, France, 94805
  • France,
    • Exelixis Clinical Site #69 Le Mans, , France, 72000
    • Exelixis Clinical Site #78 Paris, , France, 75005
    • Exelixis Clinical Site #7 Paris, , France, 75010
    • Exelixis Clinical Site #68 Paris, , France, 75013
    • Exelixis Clinical Site #72 Paris, , France, 75015
  • Germany, Nordrhein-Westfalen
    • Exelixis Clinical Site #56 Düsseldorf, Nordrhein-Westfalen, Germany, 40225
  • Germany,
    • Exelixis Clinical Site #36 Tübingen, , Germany, 72076
  • Italy, Milano
    • Exelixis Clinical Site #47 Rozzano, Milano, Italy, 20089
  • Italy,
    • Exelixis Clinical Site #25 Milano, , Italy, 20133
    • Exelixis Clinical Site #4 Milano, , Italy, 20133
  • Netherlands, Gelderland
    • Exelixis Clinical Site #12 Nijmegen, Gelderland, Netherlands, 6525 GA
  • Spain, A Coruña
    • Exelixis Clinical Site #74 Santiago De Compostela, A Coruña, Spain, 15706
  • Spain, Baleares
    • Exelixis Clinical Site #70 Palma De Mallorca, Baleares, Spain, 07120 / 07010
  • Spain,
    • Exelixis Clinical Site #75 Barcelona, , Spain, 08003
    • Exelixis Clinical Site #58 Barcelona, , Spain, 08022
    • Exelixis Clinical Site #28 Barcelona, , Spain, 08035
    • Exelixis Clinical Site #9 Barcelona, , Spain, 08035
    • Exelixis Clinical Site #73 Barcelona, , Spain, 08036
    • Exelixis Clinical Site #77 Madrid, , Spain, 28034
    • Exelixis Clinical Site #22 Madrid, , Spain, 28041
    • Exelixis Clinical Site #5 Madrid, , Spain, 28041
  • United Kingdom,
    • Exelixis Clinical Site #19 London, , United Kingdom, EC1M 6BQ

Sponsors and Collaborators

Exelixis

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03170960
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Exelixis:

Kidney

Bladder

Renal pelvis

Ureter

Urethra

Cancer

Prostate

Castration-resistant

Lung

Breast

Ovarian

Endometrial

Liver

Stomach

Additional relevant MeSH terms:

Carcinoma

Endometrial Neoplasms

Triple Negative Breast Neoplasms

Atezolizumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on September 03, 2020