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

NCT ID: NCT00878163

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2026-03-06

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 with or without gemcitabine hydrochloride in patients with unresectable solid tumors.

SECONDARY OBJECTIVES:

I. To describe the adverse events profile associated with these treatment regimens.

II. To describe the responses in patients treated with these regimens. III. To assess the effect of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 on selected biomarkers in circulating tumor cells and tumor biopsy samples from patients with metastatic pancreatic cancer.

IV. To assess the effect of erlotinib hydrochloride and Hedgehog antagonist GDC-0449 on fludeoxyglucose F 18 positron emission tomography imaging in patients with metastatic pancreatic cancer.

V. To study the association between clinical (toxicity and/or tumor response or activity) and biologic (pharmacodynamic) results associated with erlotinib hydrochloride and Hedgehog antagonist GDC-0449 in patients with metastatic pancreatic cancer.

OUTLINE: This is a dose-escalation study of erlotinib hydrochloride.

Patients receive Hedgehog antagonist GDC-0449 orally (PO) once daily (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.

Patients treated at the maximum tolerated dose undergo fludeoxyglucose F 18 positron emission tomography at baseline and on day 28. These patients also undergo tumor tissue and blood sample collection at baseline and periodically during study for correlative laboratory studies. Samples are analyzed for tyrosine phosphorylated or total MAP-K, EGFR, AKT, and other potential biomarkers of activity/response and for levels of genes transcriptionally activated (e.g., BCL-2, GLI, BFL-1/A1, 4-1BB, PTC1) by immunofluorescence, IHC, and quantitative-PCR.

After completion of study therapy, patients are followed at 3 months.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (vismodegib, erlotinib hydrochloride, gemcitabine)

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.

Group Type EXPERIMENTAL

Diagnostic Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Erlotinib Hydrochloride

Intervention Type DRUG

Given PO

Gemcitabine Hydrochloride

Intervention Type DRUG

Given IV

Vismodegib

Intervention Type DRUG

Given PO

Interventions

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Diagnostic Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Erlotinib Hydrochloride

Given PO

Intervention Type DRUG

Gemcitabine Hydrochloride

Given IV

Intervention Type DRUG

Vismodegib

Given PO

Intervention Type DRUG

Other Intervention Names

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CP 358 CP-358 Cp-358,774 CP358 OSI 774 OSI-774 OSI774 Tarceva dFdCyd Difluorodeoxycytidine Hydrochloride Gemcitabine HCI Gemzar LY 188011 LY-188011 LY188011 Erivedge GDC 0449 GDC-0449 GDC0449 Hedgehog Antagonist GDC-0449

Eligibility Criteria

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Inclusion Criteria

* 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
* Able to swallow or have medication administered through a G-tube and absorb the medication
* Participant agrees to use an acceptable form of contraception; acceptable forms of contraception:

* Latex condom (always used with spermicide)
* Diaphragm (always used with spermicide)
* Cervical cap (always used with spermicide)

Acceptable forms of secondary contraceptions, when used along with a barrier method:

* Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. "Mini-pill")
* Tubal ligation
* Partner's vasectomy
* Intrauterine device (IUD) (non-progesterone T)
* Vaginal sponge (containing spermicide)
* 100% commitment to abstinence

Unacceptable forms of contraception for women of childbearing potential:

* Oral contraception containing progestins only
* IUD progesterone T
* Female condom
* Natural family planning (rhythm method) or breastfeeding
* Fertility awareness
* Withdrawal
* Cervical shield

* Willing to abstain from smoking
* Willing to complete a daily pill diary

Exclusion Criteria

* 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
* Men or women of childbearing potential who are unwilling to employ adequate contraception until 12 months after last study drug dose
* Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \[FDA\]-approved indication and in the context of a research investigation)
* Current therapy with a CYP3A4 inhibitor or inducer
* Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy (HAART) treatment
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
* History of myocardial infarction =\< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
* More than 2 prior chemotherapy regimens for the current metastatic malignancy; full dose chemotherapy used in conjunction with concurrent radiation therapy will be included as prior therapy; Note: prior hormonal therapy (e.g. leuprolide, aromatase inhibitors, tamoxifen) will be allowed and not included as a prior chemotherapy
* Previous therapy with a hedgehog inhibitor
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charles Erlichman

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

Orlando Health Cancer Institute

Orlando, Florida, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2011-01400

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000638302

Identifier Type: -

Identifier Source: secondary_id

MAYO-MC0811

Identifier Type: -

Identifier Source: secondary_id

MC0811

Identifier Type: OTHER

Identifier Source: secondary_id

8231

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50CA102701

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01400

Identifier Type: -

Identifier Source: org_study_id

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