Clinical trial NCT00940225
Conditions: Solid Tumors Cancer
Keywords: Metastatic Breast Cancer (MBC) Melanoma Stomach or Gastroesophageal Junction Carcinoma (GEJ) Hepatocellular Carcinoma (HCC) Small Cell Lung Cancer (SCLC) Non-Small Cell Lung Cancer (NSCLC) Ovarian Cancer Pancreatic Cancer Prostate Cancer
Sponsor: Exelixis
Start date: 2009-09-01; Completion date: 2014-06-01
Enrollment: 730 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

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

Detailed description:
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.

Arms: arm 1: Open Label, cabozantinib, 100 mg, po QD for 12 weeks. arm 2: Blinded, cabozantinib, 100 mg, po QD until disease progression. arm 3: Blinded, placebo, 100 mg, po QD until disease progression. arm 4: Open Label, cabozantinib, for subjects that were on placebo during the randomized stage, 100 mg, po QD until disease progression or unacceptable toxicity. arm 5: Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity. arm 6: Open Label, cabozantinib, 39.4, po QD until disease progression or unacceptable toxicity. arm 7: Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.
Interventions: intervention 1: Cabozantinib intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents: