Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Small Cell Lung Carcinoma

Breast Neoplasms

Pancreatic Neoplasms

Melanoma

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Small Cell Lung Cancer

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Open Label, cabozantinib, 100 mg, po QD for 12 weeks.

Blinded, cabozantinib, 100 mg, po QD until disease progression.

Blinded, placebo, 100 mg, po QD until disease progression.

Open Label, cabozantinib, for subjects that were on placebo during the randomized stage, 100 mg, po QD until disease progression or unacceptable toxicity.

Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.

Open Label, cabozantinib, 39.4, po QD until disease progression or unacceptable toxicity.

Cabozantinib

Placebo

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 of Cabozantinib (XL184) in Adults With Advanced Malignancies

A Randomized Discontinuation Study of XL184 in Subjects With Advanced Solid Tumors

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.

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.

Progression Free Survival during the Randomized Stage (Randomized Population)

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.

Progression-free survival (PFS) from first dose throughout the study was estimated for all subjects (safety population) using a piecewise method.

The duration of BSR per IRF was calculated for CRPC subjects with an objective response (CR or PR) during the study.

Exelixis

Includes all tumor types from the 203 RDT cohort: castration-resistant prostate cancer (CRPC), melanoma, non-small cell lung cancer (NSCLC), pancreatic cancer, gastric/gastroesophageal junction (GEJ) cancer, hepatocellular carcinoma (HCC), small cell lung cancer (SCLC), ovarian cancer, and metastatic breast cancer

RDT All Cohorts

Subjects received a single oral daily dose of cabozantinib at 100 mg.

NRE Cohort - CRPC 100mg (Castration-Resistant Prostate Cancer)

Subjects received a single oral daily dose of cabozantinib at 39.4 mg.

NRE Cohort - CRPC 39.4mg (Castration-Resistant Prostate Cancer)

NRE Cohort - Ovarian 100mg

Eligible subjects with advanced solid tumors received open-label cabozantinib at a starting daily dose of 100 mg (freebase weight).

RDT Cohort - CRPC

RDT Cohort - Melanoma

RDT Cohort - NSCLC

RDT Cohort - Pancreatic Cancer

RDT Cohort - GEJ

RDT Cohort - HCC

RDT Cohort - SCLC

RDT Cohort - Ovarian Cancer

RDT Cohort - MBC

NRE Cohort - CRPC 100 mg

subjects received a single oral daily dose of cabozantinib at 39.4 mg.

NRE Cohort - CRPC 39.4 mg

subjects received a single oral daily dose of cabozantinib at 100 mg.

NRE Cohort - Ovarian Cancer 100mg

Total

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Exelixis Medical Information

Lead-in Stage - CRPC

Lead-in Stage - Melanoma

Lead-in Stage - NSCLC

Lead-in Stage - Pancreatic Cancer

Lead-in Stage - Gastric/GEJ

Lead-in Stage - Hepatocellular Carcinoma

Lead-in Stage - SCLC

Lead-in Stage - Ovarian Cancer

Lead-in Stage - Metastatic Breast Cancer

Lead-in Stage - NRE Ovarian Cancer

Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only

cabozantinib, 100 milligrams orally, daily for 12 weeks until progression or unacceptable toxicity.

cabozantinib, 39.4 milligrams orally, daily for 12 weeks until progression or unacceptable toxicity.

Bone Scan Response (BSR) - NRE, CRPC

cabozantinib, 100 mg, po QD, ongoing until progression

Randomized Phase - CRPC, Cabozantinib Arm

placebo 100mg, po QD, ongoing until progression

Randomized Phase - CRPC, Placebo Arm

Randomized Phase - Melanoma, Cabozantinib Arm

Placebo, 100mg, po QD, ongoing until progression

Randomized Phase - Melanoma, Placebo Arm

Randomized Phase - NSCLC, Cabozantinib Arm

placebo, 100mg, po QD, ongoing until progression

Randomized Phase - NSCLC, Placebo Arm

Randomized Phase - Pancreatic Cancer, Cabozantinib Arm

Randomized Phase - Pancreatic Cancer, Placebo Arm

Randomized Phase - Gastric/GEJ, Cabozantinib Arm

Randomized Phase - Gastric/GEJ , Placebo Arm

Randomized Phase - HCC, Cabozantinib Arm

placebo, 100 mg, po QD, ongoing until progression

Randomized Phase - HCC, Placebo Arm

Randomized Phase - SCLC, Cabozantinib Arm

Randomized Phase - SCLC, Placebo Arm

Randomized Phase - Ovarian Cancer, Cabozantinib Arm

Randomized Phase - Ovarian Cancer, Placebo Arm

Randomized Phase - MBC, Cabozantinib Arm

Randomized Phase - MBC, Placebo Arm

Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only

cabozantinib, 100 mg, po QD ongoing until progression

CRPC

NSCLC

Hepatocellular Carcinoma

Metastatic Breast Cancer

Duration of Objective Response (OR) - Responders From Lead-in Stage

NSCL

Gastric/GEJ

SCLC

Progression Free Survival (PFS) - Throughout the Study

cabozantinib, 100 milligrams po QD for 12 weeks until progression or unacceptable toxicity.

cabozantinib, 39.4 milligrams po QD for 12 weeks until progression or unacceptable toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Cabozantinib (XL184) in Adults With Advanced Malignancies	NCT00940225	Solid Tumors Cancer	Cabozantinib Placebo	18 Years -	Exelixis
Study of Cabozantinib (XL184) in Adults With Advanced Malignancies	NCT00940225	Solid Tumors Cancer	Cabozantinib Placebo	18 Years -	Exelixis
Study of Cabozantinib (XL184) in Adults With Advanced Malignancies	NCT00940225	Solid Tumors Cancer	Cabozantinib Placebo	18 Years -	Exelixis

Spots Global Cancer Trial Database for stomach or gastroesophageal junction carcinoma (gej)