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

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ClinicalTrials.gov Identifier: NCT01663272
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Tracking Information
First Submitted Date  ICMJE July 24, 2012
First Posted Date  ICMJE August 13, 2012
Results First Submitted Date  ICMJE May 18, 2017
Results First Posted Date  ICMJE September 19, 2018
Last Update Posted Date September 19, 2018
Study Start Date  ICMJE July 2012
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2013)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2012)
Maximum Tolerated Dose [ Time Frame: 4 weeks ]
The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).
Change History Complete list of historical versions of study NCT01663272 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
Median Progression-free Survival (PFS) [ Time Frame: day-7 of cycle 1 until 30 days post treatment ]
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. Patients removed from treatment for progression or other reasons will be followed for 30 days after their last dose.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2012)
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer
Official Title  ICMJE A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Publications * Zhen DB, Griffith KA, Ruch JM, Camphausen K, Savage JE, Kim EJ, Sahai V, Simeone DM, Zalupski MM. A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer. Invest New Drugs. 2016 Dec;34(6):733-739. Epub 2016 Jul 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 18, 2018)
12
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2012)
24
Actual Study Completion Date  ICMJE March 1, 2017
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01663272
Other Study ID Numbers  ICMJE UMCC 2011.105
HUM 62927 ( Other Identifier: University of Michigan IRBMED )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Michigan Rogel Cancer Center
Study Sponsor  ICMJE University of Michigan Rogel Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark Zalupski, MD University of Michigan Rogel Cancer Center
PRS Account University of Michigan Rogel Cancer Center
Verification Date September 2018

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