Gamma-Secretase Inhibitor RO4929097 and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors

NCT01145456 | Completed Phase 1

• 5 other identifiers: NCI-2011-01433CDR0000674950PHL-0788575U01CA132123
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial is studying the side effects and best dose of gamma-secretase inhibitor RO4929097 when given together with gemcitabine hydrochloride in treating patients with advanced solid tumors. Gamma-secretase inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gamma-secretase inhibitor RO4929097 together with gemcitabine hydrochloride may kill more tumor cells.

Conditions

Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose of RO4929097 in combination with gemcitabine hydrochloride, defined as the dose level in which no more than 1 of 6 patients or 0/3 experience DLT, graded according to NCI CTCAE version 4.0

  28 days

Secondary Outcomes (2)

• Cmax, Tmax, t 1/2, AUC0-24, and clearance of gamma-secretase/Notch signalling pathway inhibitor RO4929097 and gemcitabine hydrochloride when given together

  Before dosing and at 1, 2, 4, 6, 8, and 24 hours after dosing on days 1 and 10; before dosing on days 3, 9, and 15; before dosing and 1 and 2 hours after dosing on day 8; and any time on day 22 of course 1 and before drug dosing on day 1 of course 2

• Objective response according to RECIST criteria 1.1

  Up to 1 year

Study Arms (1)

Treatment (RO4929097 and gemcitabine hydrochloride)

EXPERIMENTAL

Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, 15-17, and 22-24 and 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.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Drug: gemcitabine hydrochloride; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Given orally

Also known as: R4733, RO4929097

Treatment (RO4929097 and gemcitabine hydrochloride)

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Treatment (RO4929097 and gemcitabine hydrochloride)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (RO4929097 and gemcitabine hydrochloride)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (RO4929097 and gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Meets one of the following sets of criteria:
• Histologically and/or cytologically confirmed solid malignancy
• Metastatic or unresectable disease
• Disease for which standard curative or palliative measures do not exist or are no longer effective
• Histologically and/or cytologically confirmed adenocarcinoma of the pancreas (for patients in the expansion cohort)
• Locally advanced or metastatic disease
• No prior chemotherapy for advanced disease
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• No known brain metastases
• ECOG performance status (PS) 0-1 (Karnofsky PS 60-100%)
• Life expectancy \> 12 weeks
• Hemoglobin ≥ 90 g/L (or ≥ 9 g/dL)
• Leukocytes ≥ 3,000/mm\^3
• ANC ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Philippe Bedard

  University Health Network-Princess Margaret Hospital

  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: June 15, 2010
• First Posted: June 16, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2013
• Last Updated: February 24, 2014

Record last verified: 2013-12

Locations

CA (2)