Breast Cancer Clinical Trial
Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors
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. 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.
Full 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. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy
Exploratory SAA Cohort: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent atezolizumab in CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy
Eligibility Criteria
Inclusion Criteria:
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)
Measurable disease per RECIST 1.1 as determined by the investigator.
Tumor tissue material available (archival or recent tumor biopsy)
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.
Age eighteen years or older on the day of consent.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequate organ and marrow function.
Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
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.
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 (>10 mg daily prednisone equivalent) 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.
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There are 115 Locations for this study
Gilbert Arizona, 85234, United States
Phoenix Arizona, 85054, United States
Duarte California, 91010, United States
La Jolla California, 92090, United States
Los Angeles California, 90025, United States
Newport Beach California, 92663, United States
Santa Monica California, 90404, United States
Stanford California, 94305, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
New Haven Connecticut, 06511, United States
Washington District of Columbia, 20007, United States
Jacksonville Florida, 32224, United States
Tampa Florida, 33612, United States
Atlanta Georgia, 30318, United States
Atlanta Georgia, 30341, United States
Harvey Illinois, 60426, United States
Fairway Kansas, 66205, United States
Lexington Kentucky, 40536, United States
New Orleans Louisiana, 70112, United States
Boston Massachusetts, 02215, United States
Detroit Michigan, 48201, United States
Rochester Minnesota, 55905, United States
Bolivar Missouri, 65613, United States
Kansas City Missouri, 64111, United States
Omaha Nebraska, 68130, United States
Omaha Nebraska, 68130, United States
Las Vegas Nevada, 89169, United States
Camden New Jersey, 08103, United States
East Brunswick New Jersey, 08816, United States
New Brunswick New Jersey, 08903, United States
Bronx New York, 10461, United States
East Setauket New York, 11733, United States
New York New York, 10029, United States
Cleveland Ohio, 44195, United States
Columbus Ohio, 43210, United States
Kettering Ohio, 45409, United States
Oklahoma City Oklahoma, 73104, United States
Oklahoma City Oklahoma, 73120, United States
Portland Oregon, 97213, United States
Portland Oregon, 97239, United States
Bethlehem Pennsylvania, 18015, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19111, United States
Pittsburgh Pennsylvania, 15232, United States
Charleston South Carolina, 29414, United States
Dallas Texas, 75246, United States
Dallas Texas, 75390, United States
Fort Worth Texas, 76104, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
Lubbock Texas, 79410, United States
San Antonio Texas, 78229, United States
Salt Lake City Utah, 84112, United States
Blacksburg Virginia, 24060, United States
Charlottesville Virginia, 22908, United States
Albury New South Wales, 2640, Australia
Camperdown New South Wales, 2050, Australia
Gosford New South Wales, 2250, Australia
North Ryde New South Wales, 2109, Australia
Randwick New South Wales, 2031, Australia
St Albans Victoria, 3021, Australia
Gent , 9000, Belgium
Leuven , 3000, Belgium
La Roche-sur-Yon Cedex 9, 85925, France
Villejuif Cedex, 94805, France
Bordeaux , 33076, France
Brest , 29229, France
CAEN Cedex 05 , 14076, France
Le Mans , 72000, France
Lille , 59000, France
Lyon Cedex 08 , 69373, France
Marseille , 13273, France
Nice Cedex 02 , 06189, France
Nîmes Cedex 09 , 30029, France
Paris , 75005, France
Paris , 75010, France
Paris , 75013, France
Paris , 75015, France
Saint-Grégoire , 35760, France
Strasbourg , 67000, France
Suresnes , 92150, France
Vandoeuvre les nancy , 54519, France
Düsseldorf Nordrhein-Westfalen, 40225, Germany
Tübingen , 72076, Germany
Meldola FC, 47014, Italy
Rozzano Milano, 20089, Italy
Milano , 20132, Italy
Milano , 20133, Italy
Milano , 20133, Italy
Milano , 20133, Italy
Napoli , 80131, Italy
Pavia , 27100, Italy
Roma , 00168, Italy
Nijmegen Gelderland, 6525 , Netherlands
Santiago De Compostela A Coruña, 15706, Spain
Elche Alicante, 03203, Spain
Oviedo Asturias, 33011, Spain
Palma De Mallorca Baleares, 07120, Spain
Badalona Barcelona, 08916, Spain
Sabadell Barcelona, 08208, Spain
Jeréz De La Frontera Cádiz, 11407, Spain
Pamplona Navarra, 31008, Spain
La Laguna Santa Cruz De Tenerife, 38320, Spain
Barcelona , 08003, Spain
Barcelona , 08022, Spain
Barcelona , 08023, Spain
Barcelona , 08025, Spain
Barcelona , 08035, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Girona , 17007, Spain
Madrid , 28034, Spain
Madrid , 28040, Spain
Madrid , 28040, Spain
Madrid , 28041, Spain
Madrid , 28041, Spain
Madrid , 28046, Spain
Málaga , 29010, Spain
Middlesex England, HA6 2, United Kingdom
Preston England, PR2 9, United Kingdom
Cardiff Wales, CF14 , United Kingdom
London , EC1M , United Kingdom
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