GDC-0449 and Erlotinib Hydrochloride With or Without Gemcitabine Hydrochloride in Treating Patients With Metastatic Pancreatic Cancer or Solid Tumors That Cannot Be Removed by Surgery

NCT00878163 | Active Not Recruiting Phase 1

• 8 other identifiers: NCI-2011-01400CDR0000638302MAYO-MC0811MC08118231P30CA015083P50CA102701U01CA069912
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 4

Brief Summary

This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with GDC-0449 with or without gemcitabine hydrochloride in treating patients with metastatic pancreatic cancer or solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as GDC-0449 and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving GDC-0449 together with erlotinib hydrochloride with or without gemcitabine hydrochloride may kill more tumor cells.

Conditions

Adult Solid Neoplasm; Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v6 and v7; Recurrent Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of erlotinib hydrochloride defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients

  DLT will be defined as an adverse event, according to CTCAE version 3.0, attributed (definitely, probably, or possibly to the study treatment.

  28 days

Secondary Outcomes (7)

• Adverse events as assessed by NCI CTCAE v3.0

  Up to 3 months after completion of study treatment

• Toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, graded using the NCI CTCAE version 3.0

  Up to 3 months after completion of study treatment

• Response as assessed by modified RECIST criteria

  Up to 3 months after completion of study treatment

• Time until treatment related grade 3+ toxicity

  Up to 3 months after completion of study treatment

• Time until hematologic nadirs (WBC, ANC, platelets)

  Up to 3 months after completion of study treatment

Study Arms (1)

Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)

EXPERIMENTAL

Patients receive Hedgehog antagonist GDC-0449 PO QD and erlotinib hydrochloride PO QD on days 1-28. Some patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Interventions

Gemcitabine Hydrochloride DRUG

Given IV

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

Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC 0449, GDC-0449, GDC0449, Hedgehog Antagonist GDC-0449

Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: CP 358, CP-358, Cp-358,774, CP358, OSI 774, OSI-774, OSI774, Tarceva

Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)

Diagnostic Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)

Eligibility Criteria

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

You may qualify if:

• Histologic proof of a solid tumor that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
• Metastatic adenocarcinoma of the pancreas amenable to biopsies (cohort II MTD only)
• Absolute neutrophil count (ANC) \>= 1,500/μL
• Platelets \>= 100,000/μL
• Total bilirubin =\< upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =\< 3 times upper limit of normal (ULN)
• Creatinine =\< 1.5 times ULN
• Hemoglobin \>= 9.0 g/dL
• International Normalized Ratio (INR) within normal limits (for patients treated at the MTD)
• Ability to provide informed consent
• Willingness to return to Mayo Clinic for follow up
• Life expectancy \>= 12 weeks
• Willingness to provide the biologic specimens as required by the protocol
• Negative serum pregnancy test done =\< 7 days prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• 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
• Any of the following prior therapies:
• Chemotherapy =\< 4 weeks prior to registration
• Mitomycin C/nitrosoureas =\< 6 weeks prior to registration
• Immunotherapy =\< 4 weeks prior to registration
• Biologic therapy =\< 4 weeks prior to registration
• Radiation therapy =\< 4 weeks prior to registration
• Radiation to \> 25% of bone marrow
• Failure to fully recover from acute, reversible effects of prior therapy regardless of interval since last treatment
• New York Heart Association classification III or IV
• Seizure disorder
• Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, and use of steroids, or seizure disorder
• Pregnant women
• Nursing women

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Erlotinib Hydrochloride; 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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Charles Erlichman

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 8, 2009
• Study Start: March 31, 2009
• Primary Completion: January 22, 2013
• Study Completion (Estimated): March 6, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (4)