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

This study is currently recruiting participants.
Verified January 2013 by University of Michigan Cancer Center
Sponsor:
Information provided by (Responsible Party):
Mark Zalupski, M.D., University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01663272
First received: July 24, 2012
Last updated: January 17, 2013
Last verified: January 2013
History of Changes
  Purpose

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 Intervention Phase
Pancreatic Cancer
 Drug: CABOZANTINIB
Drug: gemcitabine
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Michigan Cancer Center:

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


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: day-7 of cycle 1 until PD or death ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 24
Study Start Date: July 2012
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01663272

Contacts
Contact: Cancer AnswerLine 1-800-865-1125 canceranswerline@umich.edu

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Mark Zalupski     734-615-3969     zalupski@med.umich.edu    
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Mark Zalupski, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Mark Zalupski, M.D., Professor, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01663272     History of Changes
Other Study ID Numbers: UMCC 2011.105, HUM 62927
Study First Received: July 24, 2012
Last Updated: January 17, 2013
Health Authority: United States: Food and Drug Administration

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
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on May 16, 2013