Study of Cabozantinib (XL184) in Adults With Advanced Malignancies

Brief summary public domain (ClinicalTrials.gov)

This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types.

Detailed description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only [From initial dose through final study visit up to 44 months]. Number, percentage of participants (95% Confidence Interval). Lead-in Stage - CRPC (n=171): 4.7 (2.0 to 8.7); Lead-in Stage - Melanoma (n=77): 5.2 (1.8 to 12.4); Lead-in Stage - NSCLC (n=60): 10 (4.4 to 20.3); Lead-in Stage - Pancreatic Cancer (n=20): 0 (0 to 15.4); Lead-in Stage - Gastric/GEJ (n=21): 4.8 (0.2 to 21.8); Lead-in Stage - Hepatocellular Carcinoma (n=41): 4.9 (0.9 to 16.1); Lead-in Stage - SCLC (n=21): 4.8 (0.2 to 21.8); Lead-in Stage - Ovarian Cancer (n=70): 21.7 (13.1 to 32.4); Lead-in Stage - Metastatic Breast Cancer (n=45): 13.6 (6.0 to 25.7); Lead-in Stage - NRE Ovarian Cancer (n=60): 10.0 (3.3 to 21.8).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Bone Scan Response (BSR) - NRE, CRPC [From initial dose through final study visit up to 15 months]. Number, percentage of participants (95% Confidence Interval). NRE Cohort - CRPC 100 mg (n=93): 74.2 (64.1 to 82.7); NRE Cohort - CRPC 39.4 mg (n=51): 47.1 (32.9 to 61.5).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only [From initial dose through final study visit up to 44 months]. Median, months (95% Confidence Interval). Randomized Phase - CRPC, Cabozantinib Arm (n=14): 5.5 (4.0 to 8.5); Randomized Phase - CRPC, Placebo Arm (n=17): 1.4 (1.25 to 2.73); Randomized Phase - Melanoma, Cabozantinib Arm (n=13): 4.5 (1.8 to 15.4); Randomized Phase - Melanoma, Placebo Arm (n=13): 2.8 (1.45 to 5.45); Randomized Phase - NSCLC, Cabozantinib Arm (n=8): 2.4 (1.3 to 2.9); Randomized Phase - NSCLC, Placebo Arm (n=8): 2.4 (1.4 to 2.7); Randomized Phase - Pancreatic Cancer, Cabozantinib Arm (n=3): 2.8 (1.5 to 2.8); Randomized Phase - Pancreatic Cancer, Placebo Arm (n=3): .07 (.07 to .07); Randomized Phase - Gastric/GEJ, Cabozantinib Arm (n=3): NA (2.3 to NA) [There was only one out of three subjects evaluated; unable to estimate due to insufficient number of patients within cohort.]; Randomized Phase - Gastric/GEJ , Placebo Arm (n=2): 1.0 (.72 to 1.38); Randomized Phase - HCC, Cabozantinib Arm (n=10): 2.5 (1.3 to 6.8); Randomized Phase - HCC, Placebo Arm (n=12): 1.4 (1.3 to 4.2); Randomized Phase - SCLC, Cabozantinib Arm (n=8): 5.5 (1.9 to 6.9); Randomized Phase - SCLC, Placebo Arm (n=2): 1.5 (.85 to 2.23); Randomized Phase - Ovarian Cancer, Cabozantinib Arm (n=7): 4.9 (3.9 to 13.6); Randomized Phase - Ovarian Cancer, Placebo Arm (n=6): 1.4 (1.3 to 1.6); Randomized Phase - MBC, Cabozantinib Arm (n=5): 6.9 (5.1 to 13.5); Randomized Phase - MBC, Placebo Arm (n=5): 1.1 (.7 to 1.3).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Objective Response (OR) - Responders From Lead-in Stage [From initial dose through final study visit up to 44 months]. Median, Months (95% Confidence Interval). CRPC (n=15): 5.59 (4.27 to 8.34); Melanoma (n=6): 5.55 (2.99 to 13.86); NSCLC (n=6): 6.90 (5.29 to 10.74); Hepatocellular Carcinoma (n=3): 4.21 (2.99 to NA) [Unable to estimate due to low numbers.]; Ovarian Cancer (n=15): 11.24 (7.20 to NA) [Unable to estimate due to low numbers.]; Metastatic Breast Cancer (n=6): 3.29 (2.79 to 4.21).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS) - Throughout the Study [From initial dose through final study visit up to 44 months]. Median, months (Inter-Quartile Range). CRPC (n=171): 6.8 (3.9 to 9.7); Melanoma (n=77): 2.8 (1.4 to 6.9); NSCL (n=60): 4.0 (1.4 to 5.7); Pancreatic Cancer (n=20): 2.7 (1.3 to 5.5); Gastric/GEJ (n=21): 1.4 (1.3 to NA) [Unable to estimate as number of events is too low.]; Hepatocellular Carcinoma (n=41): 5.2 (3.6 to 9.3); SCLC (n=21): 3.4 (1.4 to 8.2); Ovarian Cancer (n=70): 5.5 (2.7 to 11.0); Metastatic Breast Cancer (n=45): 4.3 (1.4 to 8.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Bone Scan Response - NRE Cohorts, CRPC Only [From initial dose through final study visit up to 15 months]. Median, months (95% Confidence Interval). NRE Cohort - CRPC 100 mg (n=69): 5.2 (4.07 to 6.67); NRE Cohort - CRPC 39.4 mg (n=24): NA (NA to NA) [Unable to Estimate due to low numbers.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only [From initial dose through final study visit up to 15 months]. Median, months (95% Confidence Interval). NRE Cohort - CRPC 100 mg (n=93): 11.1 (9.17 to 13.34); NRE Cohort - CRPC 39.4 mg (n=51): 8.0 (7.92 to NA) [Unable to Estimate due to low numbers.]; NRE Cohort - Ovarian 100 mg (n=60): 8.5 (5.88 to 11.73).