Gemcitabine Hydrochloride With or Without Vismodegib in Treating Patients With Recurrent or Metastatic Pancreatic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01064622
First received: February 5, 2010
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

This randomized phase II trial is studying 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.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: vismodegib
Drug: gemcitabine hydrochloride
Other: hydrocortisone/placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from randomization to disease progression or death from any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated in the two treatment groups by the Kaplan-Meier (1958) method and compared using a stratified logrank test.


Secondary Outcome Measures:
  • Median overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be analyzed in a manner similar to that for PFS, i.e., via stratified logrank tests and Cox regression modeling.

  • Objective response rates [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Response rates will be compared between the combination and gemcitabine alone arm using Fisher's exact test.

  • Incidence of adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Adverse events will be summarized by type and grade and compared between groups using chisquare or Fisher exact tests, as appropriate.


Enrollment: 114
Study Start Date: September 2009
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (gemcitabine hydrochloride and placebo)
Patients 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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: hydrocortisone/placebo
Given PO
Experimental: Arm II (gemcitabine hydrochloride and vismodegib)
Patients 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.
Drug: vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog antagonist GDC-0449
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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-naïve 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
  • 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:

    • They are therapeutic on a stable warfarin dose
    • Their INR target range is no greater than 3
    • They are monitored with weekly INR testing
    • They have no active bleeding or pathological condition that carries high risk of bleeding Other anticoagulants, including enoxaparin (Lovenox) and fondaparinux (Arixtra) are also permitted
  • Women of child-bearing potential and men must use at least one form of contraception (i.e., barrier contraception) at least 4 weeks prior to study entry and then two forms of contraception (i.e barrier contraception and one other method of contraception), for the duration of study participation, and for at least 12 months post-treatment; for appropriate methods of contraception considered acceptable; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Pregnancy Testing: Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days (at initial screening/consideration for the trial - serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of GDC-0449; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing GDC-0449, the investigator must confirm and document the patient's use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of GDC-0449
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with recurrent disease after curative-intent surgical resection must have sufficient archival material for correlative studies (20 unstained 5 micron slides and 20 unstained 10 micron slides, or an archival tissue block

Exclusion Criteria:

  • 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
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GDC-0449; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with GDC-0449; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064622

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope Medical Center
Duarte, California, United States, 91010
University of Southern California
Los Angeles, California, United States, 90033
City of Hope Medical Group Inc
Pasadena, California, United States, 91105
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Evanston CCOP-NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States, 46845
United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
University of Maryland Saint Joseph Medical Center
Towson, Maryland, United States, 21204
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, New York
Montefiore Medical Center-Weiler Division
Bronx, New York, United States, 10461
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
New York University Clinical Cancer Center
New York, New York, United States, 10016-4760
New York University Langone Medical Center
New York, New York, United States, 10016
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Investigators
Principal Investigator: Hedy Kindler University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01064622     History of Changes
Other Study ID Numbers: NCI-2011-01454, NCI-2011-01454, 8418, UCCRC-8418, CDR0000655378, 09-068, 8418, N01CM00071, P30CA014599, N01CM00038
Study First Received: February 5, 2010
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone-17-butyrate
Adenocarcinoma
Carcinoma
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Gemcitabine
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 26, 2014