Gemcitabine Hydrochloride With or Without Vismodegib in Treating Patients With Recurrent or Metastatic Pancreatic Cancer
A Multi-center, Double Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine Plus GDC-0449 (NSC 747691), a Hh Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer (10052747)
12 other identifiers
interventional
118
1 country
25
Brief Summary
This randomized phase I/II trial studies gemcitabine hydrochloride and vismodegib to see how well they work compared with gemcitabine hydrochloride alone in treating patients with recurrent or metastatic pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vismodegib may slow the growth of tumor cells. It is not yet known whether giving gemcitabine hydrochloride together with vismodegib is more effective than gemcitabine hydrochloride alone in treating patients with pancreatic cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2009
Typical duration for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 3, 2009
CompletedFirst Submitted
Initial submission to the registry
February 5, 2010
CompletedFirst Posted
Study publicly available on registry
February 8, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 9, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2013
CompletedResults Posted
Study results publicly available
February 13, 2015
CompletedNovember 19, 2024
October 1, 2017
3.3 years
February 5, 2010
January 29, 2015
October 28, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival
Time from randomization to disease progression or death from any cause. Estimated in the two treatment groups by the Kaplan-Meier method and compared using a stratified logrank test.
Up to 3 years
Secondary Outcomes (4)
Overall Survival
Up to 3 years
Objective Response Rate
Up to 6 months
Incidence of Adverse Events
Up to 3 years
Activity (Overall Response Rate) in Crossover Patients
Up to 6 months
Study Arms (2)
Arm I (gemcitabine hydrochloride and placebo)
ACTIVE COMPARATORPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and placebo PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients are unblinded and may crossover to arm II.
Arm II (gemcitabine hydrochloride and vismodegib)
EXPERIMENTALPatients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and vismodegib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
- Patients must have either:
- Newly diagnosed chemo-naĂ¯ve metastatic pancreatic cancer; only patients who have not received any chemotherapy for their metastatic disease are eligible
- Recurrent disease after curative-intent surgery which has now recurred and is metastatic; patients who have recurrent disease may have received adjuvant chemotherapy or adjuvant chemoradiation, but may not have received any chemotherapy for metastatic disease; adjuvant therapy must have been completed \>= 6 months prior to the diagnosis of recurrent disease, or if not adjuvant therapy received, surgery must have been performed \>= 6 months prior to the diagnosis of recurrent disease
- Age \>= 21 years
- Life expectancy \> 3 months
- Karnofsky performance status \>= 80%
- Granulocytes \>= 1,500/mcL
- Platelet count \>= 100,000/mcL
- Total bilirubin =\< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 times upper limit of normal (ULN) (=\< 5 times ULN in the presence of liver metastases)
- Creatinine within normal institutional limit (\< 1.5) OR creatinine clearance \>= 65 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- International normalized ratio (INR) =\< 1.5 (=\< 3 for patients on warfarin)
- Patients who are on warfarin anticoagulation are allowed to participate as long as they fit the following 4 criteria:
- +8 more criteria
You may not qualify if:
- No prior chemotherapy for metastatic pancreatic cancer; patients who have received any chemotherapy and/or radiation therapy in the adjuvant setting must have completed this therapy ≥6 months prior to enrollment on the trial at the time of recurrence
- Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to hedgehog antagonist GDC-0449 or any other agents used in this study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
- GDC-0449 inhibits CYP2C8, CYP2C9, and CYP2C19 drug metabolism enzymes in vitro at concentrations that may be clinically relevant. Therefore, caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8, CYP2C9, and CYP2C19 and have narrow therapeutic windows
- Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow capsules
- Patients with clinically active liver disease, including active viral or other hepatitis or cirrhosis are ineligible
- Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia, defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
- No currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix; patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years
- Uncontrolled intercurrent illness including, but not limited to,
- Ongoing or active infection,
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
Tower Cancer Research Foundation
Beverly Hills, California, 90211, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Illinois CancerCare-Peoria
Peoria, Illinois, 61615, United States
Central Illinois Hematology Oncology Center
Springfield, Illinois, 62702, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, 46845, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
UM Saint Joseph Medical Center
Towson, Maryland, 21204, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, Marsh R, Wallace J, Kozloff M, Rajdev L, Cohen D, Wade J, Sleckman B, Lenz HJ, Stiff P, Kumar P, Xu P, Henderson L, Takebe N, Salgia R, Wang X, Stadler WM, de Sauvage FJ, Kindler HL. Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer. J Clin Oncol. 2015 Dec 20;33(36):4284-92. doi: 10.1200/JCO.2015.62.8719. Epub 2015 Nov 2.
PMID: 26527777DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Hedy Kindler, MD
- Organization
- University of Chicago
Study Officials
- PRINCIPAL INVESTIGATOR
Hedy L Kindler
University of Chicago Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2010
First Posted
February 8, 2010
Study Start
September 3, 2009
Primary Completion
December 9, 2012
Study Completion
January 31, 2013
Last Updated
November 19, 2024
Results First Posted
February 13, 2015
Record last verified: 2017-10