Gamma Secretase Inhibitor RO4929097 In Previously Treated Metastatic Pancreas Cancer

Study Overview

Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer

This phase II trial is studying how well RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) works in treating patients with previously treated metastatic pancreatic cancer. RO4929097 may stop the growth of tumor cells by blocking some enzymes needed for cell growth.

PRIMARY OBJECTIVES: I. To determine the 6-month survival of patients with previously treated metastatic pancreas cancer treated with gamma secretase RO4929097. II. To determine the adverse events of RO4929097 in this patient population. III. To correlate changes in tumor markers with RO4929097 exposure. SECONDARY OBJECTIVES: I. To evaluate the response rate and overall survival of this population treated with RO4929097. II. To correlate clinical outcome with tumor markers (including stem cell markers) obtained from pre- and post- treatment biopsies. (exploratory) III. To assess variants in genes involved in RO4929097 disposition and their relation to RO4929097 exposure. OUTLINE: This is a multicenter study. Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy at baseline and on days 16 or 17 of course one for biomarker and other correlative studies. Blood samples may also collected at baseline and periodically during study for pharmacokinetic and angiogenesis marker studies. After completion of study therapy, patients are followed up periodically for 2 years.

Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer

DRUG: gamma-secretase/Notch signalling pathway inhibitor RO4929097

NCI-2011-02537
NCI-2011-02537 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CDR0000687335
10-0273 (OTHER Identifier) (OTHER: Colorado Multiple Institutional Review Board)
8490 (OTHER Identifier) (OTHER: CTEP)
U01CA070095 (U.S. NIH Grant/Contract)
P30CA046934 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-10-30	Results First Submitted 2014-11-19	Last Update Submitted that met QC Criteria 2014-11-19
First Submitted that Met QC Criteria 2010-10-30	Results First Submitted that Met QC Criteria 2014-11-19	Last Update Posted (ESTIMATED) 2014-11-26
First Posted (ESTIMATED) 2010-11-02	Results First Posted 2014-11-26	Last Verified 2014-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (RO4929097) Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may underg	DRUG: gamma-secretase/Notch signalling pathway inhibitor RO4929097 Given PO

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (RO4929097)

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients may underg

DRUG: gamma-secretase/Notch signalling pathway inhibitor RO4929097

Given PO

Primary Outcome Measures	Measure Description	Time Frame
Survival Rate	The primary endpoint of the study was 6-month survival. The proportion of successes was estimated by the number of successes divided by the total number of evaluable patients.	6 months

Secondary Outcome Measures	Measure Description	Time Frame
Survival	Survival was estimated using the Kaplan-Meier (1958) method.	From registration to death due to any cause, assessed up to 2 years
Time to Disease Progression	Eighteen patients were evaluable for the time to disease progression endpoint.	From registration to documentation of disease progression, assessed up to 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma

Not amenable to potentially curative surgical resection
At least 1 prior regimen of chemotherapy, preferably gemcitabine-based, for metastatic disease

Evidence of disease progression
Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
Available archived tumor tissue (baseline core biopsies or surgical tumor blocks)

No diagnosis by fine-needle aspiration only
No known brain metastases
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (Karnofsky 70-100%)
White blood cell count (WBC) ≥ 3,000/mm³
Absolute neutrophil count (ANC) ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Total bilirubin normal
Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Willingness to undergo 2 tumor biopsies, if required
Fertile patients must use 2 forms of contraception (i.e., barrier contraception and one other method of contraception) ≥ 4 weeks prior to, during, and for ≥ 12 months after completion of therapy
Negative pregnancy test
Not pregnant or nursing
Able to swallow pills
No patients with 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
Not serologically positive for hepatitis A, B, or C
No history of liver disease, other forms of hepatitis, or cirrhosis
No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation
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)
No other malignancy within the past 5 years except curatively treated basal cell carcinoma of the skin or carcinoma in-situ of the uterine cervix
No combination antiretroviral therapy for HIV-positive patients
Recovered to < Common Toxicity Criteria for Adverse Effects (NCI CTCAE) grade 2 toxicities from prior therapy
More than 3 weeks since prior chemotherapy for metastatic disease (6 weeks for carmustine or mitomycin C)
At least 4 weeks since prior radiotherapy
Concurrent low-molecular weight heparin (LMWH) or full-dose coumadin allowed

International normalized ratio (INR) must be monitored as clinically indicated
No other concurrent investigational agents
No concurrent strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers, including the following:

Strong inhibitors: Amiodarone, erythromycin, clarithromycin, grapefruit juice, isoniazid, ketoconazole, itraconazole, or nefazodone

Patients taken off strong inhibitors allowed provided they have ≥ 1-week washout period
Strong inducers: Carbamazepine, pentobarbital, phenobarbital, phenytoin, Rifabutin, Rifampin, or St. John wort

Patients taken off strong inducers allowed provided they have ≥ 2-week washout period
No concurrent antiarrhythmics or other medications known to prolong QTc

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Wells Messersmith, University of Colorado Cancer Center - Anschutz Cancer Pavilion

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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