Study of Cabozantinib (XL184) in Adults With Advanced Malignancies

NCT ID: NCT00940225

Last Updated: 2024-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 730 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2014-06-30

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.

Conditions

Solid Tumors; Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lead-in Stage - cabozantinib (XL184)

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

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Randomized Stage - cabozantinib (XL184)

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

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Randomized Stage - placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Open-Label Extension - cabozantinib (XL184)

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

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg

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

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg

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

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

A. Non-Randomized Expansion (NRE) Cohort - Ovarian

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

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Interventions

Cabozantinib

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

XL184

Eligibility Criteria

Inclusion Criteria

• The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below:

• Pancreatic Cancer
• Castration-Resistant Prostate Cancer (CRPC)
• Hepatocellular Carcinoma (HCC)
• Gastric or Gastroesophageal Junction Cancer
• Melanoma
• Small Cell Lung Cancer (SCLC)
• Ovarian cancer, primary peritoneal or fallopian tube carcinoma
• Breast cancer that is one of the following subtypes: estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative), or inflammatory (regardless of receptor status) disease histology
• Non-Small Cell Lung Cancer (NSCLC)
• Certain requirements for prior therapies may apply
• The subject has documented progressive disease at screening
• Subjects having any tumor type of other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan
• The subject has recovered to baseline or CTCAE ≤ Grade 1 from toxicities related to prior treatment (some exceptions apply)
• The subject is ≥ 18 years old on the day of consent
• Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• The subject has adequate organ function
• The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
• Sexually active fertile subjects (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug(s)
• Female subjects of childbearing potential must have a negative pregnancy test at screening

Exclusion Criteria

• The subject has experienced clinically-significant hematemesis or hemoptysis of >0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• The subject has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel
• Certain restrictions on prior treatments apply
• The subject has known symptomatic or uncontrolled brain metastases or epidural disease
• The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3x)the laboratory upper limit of normal
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (low-dose aspirin (≤81 mg/day), low-dose warfarin (≤1mg/day, and prophylactic low molecular weight heparin (LMWH) are permitted)
• The subject has a corrected QT interval(QTcF)>500 ms at screening
• The subject has uncontrolled, significant intercurrent illness
• The subject is unable to swallow capsules
• The subject is pregnant or breastfeeding
• The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation
• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
• The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Dana Farber Cancer Center

Boston, Massachusetts, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Wayne State University

Detroit, Michigan, United States

University of Missouri Health Care

Columbia, Missouri, United States

Kansas City Cancer Center

Lee's Summit, Missouri, United States

Midwest Hematology Oncology Consultants

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

NYU Clinical Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University GYN Oncology

Hilliard, Ohio, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Cancer Care Associates

Tulsa, Oklahoma, United States

Northwest Cancer Specialists

Tualatin, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Cancer Centers of the Carolinas, ITOR

Greenville, South Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Texas Oncology - Central Austin Cancer Center

Austin, Texas, United States

Mary Crowley Medical Research Center

Dallas, Texas, United States

University of Texas, M. D., Anderson Cancer Center

Houston, Texas, United States

Tyler Cancer Center

Tyler, Texas, United States

Fairfax Northern Virginia Hematology Oncology

Fairfax, Virginia, United States

University of Washington

Seattle, Washington, United States

One Study Location

Brussels, , Belgium

One Study Location

Jette, , Belgium

Multiple Study Locations

Leuven, , Belgium

Liège, , Belgium

One Study Location

Mons, , Belgium

One Study Location

Jerusalem, , Israel

One Study Location

Tel Aviv, , Israel

One Study Location

Tel Litwinsky, , Israel

One Study Location

Ẕerifin, , Israel

Multiple Study Locations

Tainan City, , Taiwan

Chang Gung Medical Foundation, Taoyuan County

Taipei, , Taiwan

Taipei, , Taiwan

One Study Location

London, , United Kingdom

Countries

United States; Belgium; Israel; Taiwan; United Kingdom

References

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Other Identifiers

XL184-203

Identifier Type: -

Identifier Source: org_study_id