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

NCT ID: NCT01663272

Last Updated: 2018-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2017-03-01

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

CABOZANTINIB

Intervention Type: DRUG

Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

gemcitabine

Intervention Type: DRUG

Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.

Interventions

CABOZANTINIB

Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.

Intervention Type: DRUG

gemcitabine

Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.

Intervention Type: DRUG

Other Intervention Names

XL184; Gemzar

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Zalupski, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Countries

United States

References

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. doi: 10.1007/s10637-016-0376-1. Epub 2016 Jul 21.

Reference Type: RESULT

PMID: 27439894 (View on PubMed)

Other Identifiers

HUM 62927

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2011.105

Identifier Type: -

Identifier Source: org_study_id