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A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01663272
Recruitment Status : Active, not recruiting
First Posted : August 13, 2012
Last Update Posted : March 21, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Gemcitabine is considered one of the standard drugs for advanced pancreatic cancer and is approved by the FDA to treat it. Cabozantinib is a new drug that has demonstrated effectiveness against pancreatic cancer in laboratory experiments, especially when given with gemcitabine. Initial studies with cabozantinib in pancreatic cancer have shown some activity against the disease. The purpose of this study is to determine the safest and highest dose of cabozantinib that can be given together with standard doses of gemcitabine in patients with pancreatic cancer. This study will determine the safety and tolerability of this two drug combination.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: CABOZANTINIB Drug: gemcitabine Phase 1

Detailed Description:

Preclinical work at the University of Michigan has demonstrated that inhibition of c-Met with cabozantinib prevented the development of metastatic disease in an intra-cardiac injection model in NOD/SCID mice. Additionally, the combination of cabozantinib and gemcitabine demonstrated improved tumor control compared to either agent alone in a relevant orthotopic implantation mouse model.

Combining gemcitabine with the c-Met inhibitor cabozantinib in advanced pancreatic cancer is a novel strategy that takes advantage of an established cytotoxic agent with one that targets a pathway known to be important for the growth, dissemination, and resistance of this disease.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer
Study Start Date : July 2012
Primary Completion Date : January 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: cabozantinib with gemcitabine
The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity
Drug: CABOZANTINIB
Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.
Other Name: XL184
Drug: gemcitabine
Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.
Other Name: Gemzar


Outcome Measures

Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: 5 weeks ]
    The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: day-7 of cycle 1 until PD or death ]
    Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death


Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. pathologically confirmed pancreatic carcinoma.
  2. locally advanced unresectable disease, metastatic disease, or recurrent disease following surgical therapy.
  3. ≥ 18 years old.
  4. Life expectancy of greater than 12 weeks.
  5. ECOG performance status ≤1 (Karnofsky ≥70%) (See Appendix A).
  6. adequate organ and marrow function as follows:
  7. capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  8. use medically accepted barrier methods of contraception
  9. women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

  1. neuroendocrine tumors of the pancreas.
  2. more than 1 prior systemic treatment regimen for pancreatic cancer. may have received prior neoadjuvant or adjuvant therapy, including gemcitabine, provided 6 months have elapsed from completion of that treatment and the start of study therapy.
  3. Previous gemcitabine therapy for advanced pancreatic cancer. Patients who have had chemotherapy within 4 weeks, nitrosoureas/mitomycin C within 6 weeks, or monoclonal antibody within 6 weeks prior to planned initiation of study treatment.
  4. prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.
  5. have received an investigational agent within 28 days of the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is longer.
  6. have received radiation therapy within 14 days of study treatment.
  7. have not recovered from toxicity due to all prior therapies (i.e., return to pretherapy baseline or to CTCAE Grade 0 or 1) except alopecia and non-clinically significant AEs.
  8. known brain metastases.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01663272


Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Mark Zalupski, MD University of Michigan Cancer Center
More Information

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01663272     History of Changes
Other Study ID Numbers: UMCC 2011.105
HUM 62927 ( Other Identifier: University of Michigan IRBMED )
First Posted: August 13, 2012    Key Record Dates
Last Update Posted: March 21, 2016
Last Verified: March 2016

Keywords provided by University of Michigan Cancer Center:
oncology
pancrease

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs