Vismodegib and Gemcitabine Hydrochloride in Treating Patients With Advanced Pancreatic Cancer

NCT01195415 | Completed Phase 2 Results DMC

• 4 other identifiers: NCI-2011-03746UMCC 2010-0038417P30CA046592
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies vismodegib and gemcitabine hydrochloride in treating patients with advanced pancreatic cancer. Vismodegib may stop the growth of pancreatic cancer by blocking blow flow to the tumor. Gemcitabine hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib and gemcitabine hydrochloride may kill more tumor cells.

Conditions

Recurrent Pancreatic Carcinoma; Stage IV Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Median Percent at Baseline and 3 Weeks in CD44+/ CD24+/ ESA+ Cells From Needle Biopsy Calculated Using FACS

  The median percentage of CD44+CD24+ESA+ cells from needle biopsy were calculated at baseline and at 3 weeks using FACS. The difference between the two time points was calculated.

  3 weeks

Secondary Outcomes (3)

• The Number of Participants With an Objective Best Response (CR + PR)

  Up to 4 weeks

• Median Progression Free Survival

  Up to 24 months

• Percentage of Treated Patients Experiencing Grade 3+ Toxicity Per National Cancer Institute Common Toxicity Criteria (CTC) Version 3.0

  Up to 4 weeks

Study Arms (1)

Treatment (vismodegib, gemcitabine hydrochloride)

EXPERIMENTAL

Patients receive vismodegib PO QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 (beginning in course 2). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Vismodegib

Interventions

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Treatment (vismodegib, gemcitabine hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vismodegib, gemcitabine hydrochloride)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

Treatment (vismodegib, gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed pancreas cancer
• Patients must have metastatic disease or recurrent disease following surgical therapy
• 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) \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• Patients must have disease accessible for core needle biopsy both prior to initiation of therapy and on day 21 (+ or - 1 day) of GDC-0449 treatment
• No previous systemic therapy for metastatic pancreas cancer is permitted; prior neoadjuvant or adjuvant therapy with chemotherapy and/or radiation is allowed provided that the last day of therapy was at least 6 months prior to registration
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 2.0 mg/dl
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal; \< 5 x if liver involved in tumor
• Creatinine \< 2.0 mg/dl
• The effects of GDC-0449 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because hedgehog (Hh) signal pathway inhibitors as well as gemcitabine are known to be teratogenic, women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, 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: omen of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL beta-human chorionic gonadotropin \[bHCG\]) within 10-14 days and within 24 hours prior to the first dose of GDC-0449 (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

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 6 months prior to entering the study or those who have not recovered from adverse events due to agents administered more than 6 months earlier
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study
• Patients on anticoagulation with Coumadin are ineligible; however anticoagulation with enoxaparin is acceptable for study entry
• 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 hypomagnesemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
• Patients with \> grade 1 hyponatremia or hypocalcemia are excluded from this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because GDC-0449 is a Hh pathway inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GDC-0449, 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Kim EJ, Sahai V, Abel EV, Griffith KA, Greenson JK, Takebe N, Khan GN, Blau JL, Craig R, Balis UG, Zalupski MM, Simeone DM. Pilot clinical trial of hedgehog pathway inhibitor GDC-0449 (vismodegib) in combination with gemcitabine in patients with metastatic pancreatic adenocarcinoma. Clin Cancer Res. 2014 Dec 1;20(23):5937-5945. doi: 10.1158/1078-0432.CCR-14-1269. Epub 2014 Oct 2.

  PMID: 25278454 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; HhAntag691

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; 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

Results Point of Contact

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

zalupski@umich.edu

734-615-3969

Study Officials

• Mark Zalupski

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2010
• First Posted: September 6, 2010
• Study Start: June 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: October 10, 2014
• Last Updated: August 7, 2017
• Results First Posted: October 7, 2015

Record last verified: 2017-08

Locations

US (1)