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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University of Michigan Cancer Center
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01663272
First received: July 24, 2012
Last updated: October 16, 2014
Last verified: October 2014

July 24, 2012
October 16, 2014
July 2012
May 2015   (final data collection date for primary outcome measure)
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).
Maximum tolerated dose [ Time Frame: 4 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).
Complete list of historical versions of study NCT01663272 on ClinicalTrials.gov Archive Site
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
Same as current
Not Provided
Not Provided
 
A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer
A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • 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
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
Interventions:
  • Drug: CABOZANTINIB
  • Drug: gemcitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
January 2019
May 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Cancer AnswerLine 1-800-865-1125 canceranswerline@umich.edu
United States
 
NCT01663272
UMCC 2011.105, HUM 62927
Yes
University of Michigan Cancer Center
University of Michigan Cancer Center
Not Provided
Principal Investigator: Mark Zalupski, MD University of Michigan Cancer Center
University of Michigan Cancer Center
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP