Overview

This trial is active, not recruiting.

Conditions adenocarcinoma of the pancreas, recurrent pancreatic cancer, stage iv pancreatic cancer
Treatments gamma-secretase/notch signalling pathway inhibitor ro4929097, diagnostic laboratory biomarker analysis, pharmacological study
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date October 2010
End date July 2012
Trial size 21 participants
Trial identifier NCT01232829, 10-0273, 8490, CDR0000687335, NCI-2011-02537, P30CA046934, U01CA070095, UCHSC-10-0273

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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 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.
gamma-secretase/notch signalling pathway inhibitor ro4929097 R4733
Given PO
diagnostic laboratory biomarker analysis
Correlative studies
pharmacological study pharmacological studies
Correlative studies

Primary Outcomes

Measure
Survival rate
time frame: 6 months

Secondary Outcomes

Measure
Survival
time frame: From registration to death due to any cause, assessed up to 2 years
Tumor response (complete or partial response) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart
time frame: Up to 2 years
Time to disease progression
time frame: From registration to documentation of disease progression, assessed up to 2 years
Duration of response
time frame: From the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 2 years
Time to treatment failure
time frame: From the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 2 years
Adverse events
time frame: Up to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 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 - ECOG performance status (PS) 0-1 (Karnofsky 70-100%) - WBC ≥ 3,000/mm³ - ANC ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Hemoglobin ≥ 9 g/dL - Total bilirubin normal - AST and 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 < 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 - INR must be monitored as clinically indicated - No other concurrent investigational agents - No concurrent strong 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

Additional Information

Official title A Phase II Study of the Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer
Principal investigator Wells Messersmith
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).