This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types.
The goal of this clinical trial was to learn about the efficacy, safety, and tolerability of cabozantinib against a placebo in subjects with Metastatic Breast Cancer (MBC), Gastric and Gastroesophageal Junction Cancer (GEJ), Hepatocellular Carcinoma (HCC), Melanoma, Non-small Cell Lung Cancer (NSCLC), Ovarian (primary peritoneal or fallopian tube carcinoma), Pancreatic Cancer, Castration-Resistant Prostate Cancer (CRPC), or Small cell Lung Cancer (SCLC) with advanced tumors. The main questions this study aimed to answer were: * What is the efficacy of cabozantinib in subjects with advanced solid tumors? * What is the safety and efficacy of cabozantinib at two starting dose levels 100 milligrams (mg) once daily (po QD) and 39.4 mg po QD? Please note: that the 39.4 mg, po QD was only used in the Non-Randomized Expansion (NRE) part of the study There were three stages to the Randomized Discontinuation Trial (RDT): 1. The Lead in Stage: This stage enrolled eligible patients with advanced solid tumors who received open-label cabozantinib at 100 mg once daily for 12 weeks. 2. The Randomized Stage: Subjects who demonstrated stable disease (SD) at the end of 12 weeks of the Lead-in Stage were randomized to receive cabozantinib or placebo (a look-alike substance that contains no active drug) in a blinded manner. After randomization, when a patient developed progressive disease (PD), study treatments were discontinued and the treatment blind was broken. If the subject was on a placebo, the subject was offered the opportunity to receive cabozantinib. If the subject was already on cabozantinib, the subject entered the Post-Treatment Period where they were followed until death. 3. Open-Label Extension: Subjects who were deemed with partial response (PR) or complete response (CR) at Week 12 of the Lead-In Stage were not randomized but allowed to participate in the "Open Label Extension". Patients were given the cabozantinib treatment of 100 mg, po QD. The emerging data supported enrollment in an open-label, Non-Randomized Expansion cohort (NRE). These cohorts targeted patients with prostate and ovarian cancers. For the patients with prostate, they were assigned to either 100 mg, po QD or 39.4 mg, po QD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
730
Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only
Objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.0 per investigator The analysis of ORR in the RDT Cohorts were defined as the proportion of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per mRECIST 1.0 during the 12-week Lead-In Stage. In the NRE Ovarian Cohort, mRECIST 1.1 was used. ORR for the NRE CRPC Cohorts was not a primary objective and is therefore not captured in the table below.
Time frame: From initial dose through final study visit up to 44 months
Bone Scan Response (BSR) - NRE, CRPC
The reduction of bone scan lesion area (BSLA) by \> 30% was used as the quantitative measure of BSR. BSR was a primary outcome measure for only the NRE CRPC Cohorts.
Time frame: From initial dose through final study visit up to 15 months
Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only
Progression Free Survival during the Randomized Stage (Randomized Population)
Time frame: From initial dose through final study visit up to 44 months
Duration of Objective Response (OR) - Responders From Lead-in Stage
Duration of objective response was defined as the time from the tumor assessment that first documented PR or CR that was subsequently confirmed at least 28 days later until the date of documented progression. There were either few or no responders in the Gastric/GEJ, SCLC, and pancreatic cohorts so these cohorts are excluded.
Time frame: From initial dose through final study visit up to 44 months
Progression Free Survival (PFS) - Throughout the Study
Progression-free survival (PFS) from first dose throughout the study was estimated for all subjects (safety population) using a piecewise method.
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Pinnacle Oncology of Arizona
Scottsdale, Arizona, United States
University of California Davis Cancer Center
Sacramento, California, United States
University of California, San Francisco
San Francisco, California, United States
Stanford University Medical Center
Stanford, California, United States
Rocky Mountain Cancer Centers
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Florida Cancer Specialists
Fort Myers, Florida, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
Medical College of Georgia
Augusta, Georgia, United States
Central Indiana Cancer Centers
Indianapolis, Indiana, United States
...and 37 more locations
Time frame: From initial dose through final study visit up to 44 months
Duration of Bone Scan Response - NRE Cohorts, CRPC Only
The duration of BSR per IRF was calculated for CRPC subjects with an objective response (CR or PR) during the study.
Time frame: From initial dose through final study visit up to 15 months
Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only
Time frame: From initial dose through final study visit up to 15 months