Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00940225
Other study ID # XL184-203
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date September 2009
Est. completion date June 2014

Study information

Verified date December 2023
Source Exelixis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Completed
Enrollment 730
Est. completion date June 2014
Est. primary completion date May 2013
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Cabozantinib

Placebo


Locations

Country Name City State
Belgium One Study Location Brussels
Belgium One Study Location Jette
Belgium Multiple Study Locations Leuven
Belgium One Study Location Mons
Israel One Study Location Jerusalem
Israel One Study Location Tel Aviv
Israel One Study Location Tel-Hashomer
Israel One Study Location Zerifin
Taiwan Multiple Study Locations Tainan City
Taiwan Chang Gung Medical Foundation, Taoyuan County Taipei
United Kingdom One Study Location London
United States University of Michigan Health System Ann Arbor Michigan
United States Medical College of Georgia Augusta Georgia
United States Texas Oncology - Central Austin Cancer Center Austin Texas
United States Dana Farber Cancer Center Boston Massachusetts
United States University of Missouri Health Care Columbia Missouri
United States Mary Crowley Medical Research Center Dallas Texas
United States Rocky Mountain Cancer Centers Denver Colorado
United States Wayne State University Detroit Michigan
United States Duke University Medical Center Durham North Carolina
United States Fairfax Northern Virginia Hematology Oncology Fairfax Virginia
United States Florida Cancer Specialists Fort Myers Florida
United States Cancer Centers of the Carolinas, ITOR Greenville South Carolina
United States Ohio State University GYN Oncology Hilliard Ohio
United States University of Texas, M. D., Anderson Cancer Center Houston Texas
United States Central Indiana Cancer Centers Indianapolis Indiana
United States Comprehensive Cancer Centers of Nevada Las Vegas Nevada
United States Kansas City Cancer Center Lee's Summit Missouri
United States Mount Sinai Comprehensive Cancer Center Miami Beach Florida
United States Sarah Cannon Research Institute Nashville Tennessee
United States Yale University School of Medicine New Haven Connecticut
United States Tulane University Health Sciences Center New Orleans Louisiana
United States Memorial Sloan Kettering Cancer Center New York New York
United States NYU Clinical Cancer Center New York New York
United States University of Oklahoma Oklahoma City Oklahoma
United States University of Pennsylvania Philadelphia Pennsylvania
United States University of California Davis Cancer Center Sacramento California
United States Midwest Hematology Oncology Consultants Saint Louis Missouri
United States University of California, San Francisco San Francisco California
United States Pinnacle Oncology of Arizona Scottsdale Arizona
United States University of Washington Seattle Washington
United States Stanford University Medical Center Stanford California
United States Northwest Cancer Specialists Tualatin Oregon
United States Cancer Care Associates Tulsa Oklahoma
United States Tyler Cancer Center Tyler Texas

Sponsors (1)

Lead Sponsor Collaborator
Exelixis

Countries where clinical trial is conducted

United States,  Belgium,  Israel,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
From initial dose through final study visit up to 44 months
Primary 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. From initial dose through final study visit up to 15 months
Primary Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only Progression Free Survival during the Randomized Stage (Randomized Population) From initial dose through final study visit up to 44 months
Secondary 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. From initial dose through final study visit up to 44 months
Secondary 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. From initial dose through final study visit up to 44 months
Secondary 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. From initial dose through final study visit up to 15 months
Secondary Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only From initial dose through final study visit up to 15 months
See also
  Status Clinical Trial Phase
Recruiting NCT05346796 - Survivorship Plan HEalth REcord (SPHERE) Implementation Trial N/A
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Completed NCT04867850 - Effect of Behavioral Nudges on Serious Illness Conversation Documentation N/A
Enrolling by invitation NCT04086251 - Remote Electronic Patient Monitoring in Oncology Patients N/A
Completed NCT01285037 - A Study of LY2801653 in Advanced Cancer Phase 1
Completed NCT00680992 - Study of Denosumab in Subjects With Giant Cell Tumor of Bone Phase 2
Completed NCT00062842 - Study of Irinotecan on a Weekly Schedule in Children Phase 1
Active, not recruiting NCT04548063 - Consent Forms in Cancer Research: Examining the Effect of Length on Readability N/A
Completed NCT04337203 - Shared Healthcare Actions and Reflections Electronic Systems in Survivorship N/A
Recruiting NCT04349293 - Ex-vivo Evaluation of the Reactivity of the Immune Infiltrate of Cancers to Treatments With Monoclonal Antibodies Targeting the Immunomodulatory Pathways N/A
Terminated NCT02866851 - Feasibility Study of Monitoring by Web-application on Cytopenia Related to Chemotherapy N/A
Active, not recruiting NCT05304988 - Development and Validation of the EFT for Adolescents With Cancer
Completed NCT04448041 - CRANE Feasibility Study: Nutritional Intervention for Patients Undergoing Cancer Surgery in Low- and Middle-Income Countries
Completed NCT00340522 - Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development
Recruiting NCT04843891 - Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis. Phase 1
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Completed NCT03167372 - Pilot Comparison of N-of-1 Trials of Light Therapy N/A
Completed NCT03109041 - Initial Feasibility Study to Treat Resectable Pancreatic Cancer With a Planar LDR Source Phase 1
Terminated NCT01441115 - ECI301 and Radiation for Advanced or Metastatic Cancer Phase 1
Recruiting NCT06206785 - Resting Energy Expenditure in Palliative Cancer Patients