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

NCT01663272 | Completed Phase 1 Results DMC

• 2 other identifiers: UMCC 2011.105HUM 62927
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

oncology; pancrease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Median Progression-free Survival (PFS)

  day-7 of cycle 1 until 30 days post treatment

Study Arms (1)

cabozantinib with gemcitabine

EXPERIMENTAL

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; Drug: gemcitabine

Interventions

CABOZANTINIB DRUG

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

Also known as: XL184

cabozantinib with gemcitabine

gemcitabine DRUG

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

Also known as: Gemzar

cabozantinib with gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• pathologically confirmed pancreatic carcinoma.
• locally advanced unresectable disease, metastatic disease, or recurrent disease following surgical therapy.
• ≥ 18 years old.
• Life expectancy of greater than 12 weeks.
• ECOG performance status ≤1 (Karnofsky ≥70%) (See Appendix A).
• adequate organ and marrow function as follows:
• capable of understanding and complying with the protocol requirements and has signed the informed consent document.
• use medically accepted barrier methods of contraception
• women of childbearing potential must have a negative pregnancy test at screening.

You may not qualify if:

• neuroendocrine tumors of the pancreas.
• 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.
• 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.
• 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.
• 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.
• have received radiation therapy within 14 days of study treatment.
• 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.
• known brain metastases.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

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

  PMID: 27439894 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Interventions

cabozantinib; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The MTD could not be determined as too many patients experienced toxicity.

Results Point of Contact

• Title: Dr. Mark Zalupski, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

zalupski@med.umich.edu

734-647-8902

Study Officials

• Mark Zalupski, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2012
• First Posted: August 13, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: March 1, 2017
• Last Updated: September 19, 2018
• Results First Posted: September 19, 2018

Record last verified: 2018-09

Locations

US (1)