Study of Cabozantinib (XL184) in Adults With Advanced Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT00940225
First received: July 12, 2009
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine whether or not XL184 demonstrates anti-tumor activity in selected tumor types under a randomized discontinuation trial (RDT) design. Subjects who have responded to study drug after 12 weeks of open-label XL184 administration will continue to take XL184. Subjects who are clearly progressing will discontinue study treatment and subjects who demonstrate stable disease will be randomized to either XL184 or placebo. For individual patients, once disease progression is observed, the blind will be broken and subjects who were randomized to placebo will be offered the option to receive open-label XL184. Subjects who progressed while taking XL184 will discontinue study treatment.

Emerging data may support enrollment in an open-label, non-randomized expansion cohort (NRE). There will be NRE cohorts for prostate and ovarian cancers.


Condition Intervention Phase
Solid Tumors
Cancer
Drug: XL184
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Discontinuation Study of XL184 in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • To evaluate the efficacy of XL184 in subjects with advanced solid tumors [ Time Frame: Assessed approximately every 6 weeks using MRI, CT, and/or bone scans ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of XL184 in subjects with advanced solid tumors [ Time Frame: Assessed approximately every 3 weeks, during study visits ] [ Designated as safety issue: Yes ]
  • To correlate the pathway dysfunction of disease-related genes or proteins such as MET and downstream signaling molecules with clinical outcome [ Time Frame: Assessed approximately every 6 weeks through blood samples and tumor biopsies ] [ Designated as safety issue: No ]
  • To further characterize the pharmacokinetic (PK) and pharmacodynamic parameters of XL184 [ Time Frame: Assessed approximately every 6 weeks through blood samples ] [ Designated as safety issue: No ]

Estimated Enrollment: 1300
Study Start Date: August 2009
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
RDT Open-Label
Drug: XL184
All subjects receive 100 mg XL184 (supplied at 19.7-, 50-, and 60-mg strength capsules) daily for 12 weeks. Subjects with a partial or complete response will continue daily XL184 administration until disease progression. Subjects with stable disease will be randomized to Arm 2 or 3.
Experimental: Arm 2
RDT Randomized Blinded-XL184
Drug: XL184
After 12 weeks of open-label daily XL184, subjects with stable disease randomized to Arm 2 will continue to receive XL184 (blinded) administered daily until disease progression.
Placebo Comparator: Arm 3
RDT Randomized Blinded
Drug: Placebo
After 12 weeks of open-label daily XL184, subjects with stable disease randomized to Arm 3 will receive capsules of placebo that are size- and color-matched to XL184 administered daily until disease progression. Subjects will be unblinded at disease progression and, if found to be receiving placebo, given the option to receive XL184.
Experimental: Non-Randomized Expansion (NRE) Cohorts
Drug: XL184
Drug: XL184
All subjects receive open-label, 100 mg XL184 (supplied at 19.7-, 50-, and 60 mg strength capsules) daily until disease progression.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment
  • 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 has a corrected QT interval(QTcF)>500 ms at screening
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00940225

  Hide Study Locations
Locations
United States, Arizona
Pinnacle Oncology of Arizona
Scottsdale, Arizona, United States, 85258
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
University of California, San Francisco
San Francisco, California, United States, 94115
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
Florida Cancer Specialists
Fort Meyers, Florida, United States, 33916
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Indiana
Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46227
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Dana Farber Cancer Center
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Wayne State University
Detroit, Michigan, United States, 48201
United States, Missouri
University of Missouri Health Care
Columbia, Missouri, United States, 65203
Kansas City Cancer Center
Lee's Summit, Missouri, United States, 64064
Midwest Hematology Oncology Consultants
St. Louis, Missouri, United States, 63136
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
NYU Clinical Cancer Center
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State University GYN Oncology
Hilliard, Ohio, United States, 43026
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73190
Cancer Care Associates
Tulsa, Oklahoma, United States, 74104
United States, Oregon
Northwest Cancer Specialists
Tualatin, Oregon, United States, 97062
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Cancer Centers of the Carolinas, ITOR
Greenville, South Carolina, United States, 29605
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology - Central Austin Cancer Center
Austin, Texas, United States, 78731
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
University of Texas, M. D., Anderson Cancer Center
Houston, Texas, United States, 77030
Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Virginia
Fairfax Northern Virginia Hematology Oncology
Fairfax, Virginia, United States, 22031
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Belgium
One Study Location
Brussels, Belgium
One Study Location
Jette, Belgium
Multiple Study Locations
Leuven, Belgium
Liege, Belgium
One Study Location
Mons, Belgium
Israel
One Study Location
Jerusalem, Israel
One Study Location
Tel Aviv, Israel
One Study Location
Tel-Hashomer, Israel
One Study Location
Zerifin, Israel
Taiwan
Multiple Study Locations
Tainan City, Taiwan
Taipei, Taiwan
Taoyuan County, Taiwan
United Kingdom
One Study Location
London, United Kingdom
Sponsors and Collaborators
Exelixis
  More Information

No publications provided by Exelixis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00940225     History of Changes
Other Study ID Numbers: XL184-203
Study First Received: July 12, 2009
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Israel: Ministry of Health
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Exelixis:
Breast Cancer
Melanoma
Stomach or Gastroesophageal Junction Carcinoma
Hepatocellular Carcinoma (HCC)
Small Cell Lung Cancer (SCLC)
Non-Small Cell Lung Cancer (NSCLC)
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer

ClinicalTrials.gov processed this record on October 23, 2014