RO4929097 Before Surgery in Treating Patients With Pancreatic Cancer

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

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Brief Summary

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This phase I trial is studying the side effects of RO4929097 before surgery in treating patients with pancreatic cancer. RO4929097 may stop the growth of tumor cells by blocking some enzymes needed for cell growth. Giving RO4929097 before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate the effects of neoadjuvant gamma-secretase inhibitor RO4929097 on Notch inhibition via interrogation of Hes-1 expression in patients with pancreatic cancer.

SECONDARY OBJECTIVES:

I. To evaluate the effects of this regimen on pancreatic cancer stem cell self-renewal and tumorigenesis as compared to pancreatic stem cells from controls (patients who do not receive treatment).

II. To evaluate the safety of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral gamma-secretase inhibitor RO4929097 on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Beginning 7 days after completion of gamma-secretase inhibitor RO4929097, patients undergo complete resection comprising pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy based on the anatomic location of the cancer. Tumor tissue from biopsy and surgery and blood samples are collected periodically for pharmacodynamic studies.

After completion of study therapy, patients are followed up every 6 months for 1 year.

Conditions

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Adenocarcinoma of the Pancreas Stage IA Pancreatic Cancer Stage IB Pancreatic Cancer Stage IIA Pancreatic Cancer Stage IIB Pancreatic Cancer

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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Arm I

Patients receive oral gamma-secretase inhibitor RO4929097 on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Beginning 7 days after completion of gamma-secretase inhibitor RO4929097, patients undergo complete resection comprising pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy based on the anatomic location of the cancer. Tumor tissue from biopsy and surgery and blood samples are collected periodically for pharmacodynamic studies.

Group Type EXPERIMENTAL

gamma-secretase/Notch signalling pathway inhibitor RO4929097

Intervention Type DRUG

Given orally

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

pharmacological study

Intervention Type OTHER

Correlative studies

neoadjuvant therapy

Intervention Type PROCEDURE

therapeutic conventional surgery

Intervention Type PROCEDURE

Interventions

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gamma-secretase/Notch signalling pathway inhibitor RO4929097

Given orally

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

pharmacological study

Correlative studies

Intervention Type OTHER

neoadjuvant therapy

Intervention Type PROCEDURE

therapeutic conventional surgery

Intervention Type PROCEDURE

Other Intervention Names

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R4733 RO4929097 pharmacological studies

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed pancreatic adenocarcinoma

* T1-3, N0-1, and M0 disease
* Surgically resectable disease confirmed by a surgeon experienced in pancreatic surgery

* No borderline resectable disease defined as any of the following:

* Tumors with severe unilateral or bilateral SMV/portal involvement impingement
* Abutment (or) encasement of hepatic artery
* SMA or celiac encasement (or) presence of SMV occlusion by tumor
* No metastatic disease
* ECOG performance status 0-1
* Life expectancy \> 6 months
* WBC ≥ 3,000/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 9 g/dL
* Total bilirubin ≤ 2 mg/dL
* AST and ALT ≤ 2.5 times upper limit of normal
* Creatinine ≤ 2 mg/dL
* Calcium, magnesium, phosphorous, and potassium normal
* Negative pregnancy test
* Not pregnant or nursing
* Fertile patients must use effective barrier-method contraception 4 weeks before, during, and for ≥ 12 months after completion of treatment
* Able to swallow tablets
* No malabsorption syndrome or other condition that would interfere with intestinal absorption
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or other agents used in the study
* No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation

* Grade 1 hyponatremia with sodium ≤ 131 mg/dL is permissible
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

* Ongoing or active infection
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Cardiac arrhythmia other than chronic
* Stable atrial fibrillation
* Psychiatric illness/social situations that would limit compliance with study requirements
* No baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female)
* Patients with a prior cancer with evidence of active cancer are excluded from this study

* Patients with a prior cancer are permitted to enter this study as long as there is no documented evidence of active malignancy
* No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, and hypokalemia
* No symptomatic congestive heart failure, unstable angina pectoris, and a history of torsades de pointes or other significant cardiac arrhythmias
* No requirement for antiarrhythmics or other medications known to prolong QTc
* No other concurrent anticancer agents or therapies
* Recovered to \< grade 2 toxicity related to prior therapy
* No prior chemotherapy or radiotherapy for pancreatic cancer
* No other concurrent investigational agents
* No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®), ketoconazole, or grapefruit juice
* No concurrent strong inducers or inhibitors of CYP3A4
* No concurrent combination antiretroviral therapy for HIV-positive patients

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edward Kim

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

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Tower Cancer Research Foundation

Beverly Hills, California, United States

Site Status

City of Hope Medical Center

Duarte, California, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

Fort Wayne, Indiana, United States

Site Status

Countries

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United States