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

• 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: University of Michigan Rogel Cancer Center
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

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: 12 participants
• Allocation: N/A
• 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
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: March 1, 2017

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. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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

Locations

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Mark Zalupski, MD; University of Michigan Rogel Cancer Center

More Information

Publications of Results:

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.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT01663272
• Other Study ID Numbers: UMCC 2011.105; HUM 62927 ( Other Identifier: University of Michigan IRBMED )
• First Posted: August 13, 2012
• Results First Posted: September 19, 2018
• Last Update Posted: September 19, 2018
• Last Verified: September 2018

Keywords provided by University of Michigan Rogel 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