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

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CABOZANTINIB

gemcitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring oncology, pancrease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

University of Michigan Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cabozantinib with gemcitabine

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose

The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01663272

First Posted

July 24, 2012

Last Updated

September 18, 2018

Sponsor

University of Michigan Rogel Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT01663272

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

July 2012 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

March 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

Keywords

oncology, pancrease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cabozantinib with gemcitabine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

CABOZANTINIB

Other Intervention Name(s)

XL184

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose

Description

The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).

Time Frame

5 weeks

Secondary Outcome Measure Information:

Title

Median Progression-free Survival (PFS)

Description

Time Frame

day-7 of cycle 1 until 30 days post treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Zalupski, MD

Organizational Affiliation

University of Michigan Rogel Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Comprehensive Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27439894

Citation

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.

Results Reference

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

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