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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01663272
• Other study ID #: UMCC 2011.105
• Secondary ID: HUM 62927
• Status: Completed
• Phase: Phase 1
• Start date: July 2012
• Est. completion date: March 1, 2017

Study information

• Verified date: September 2018
• Source: University of Michigan Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 1, 2017
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• CABOZANTINIB
Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.
• gemcitabine
Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose	The MTD is defined at the highest dose level at which =25% of patients experience a dose-limiting toxicity (DLT).	5 weeks
Secondary	Median Progression-free Survival (PFS)	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.	day-7 of cycle 1 until 30 days post treatment