Gamma-Secretase Inhibitor RO4929097 in Treating Patients With Metastatic or Unresectable Solid Malignancies

NCT01096355 | Completed Phase 1

• 6 other identifiers: NCI-2011-01550CDR0000666959PMH-PJC-003PJC-0038501U01CA132123
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial is studying the side effects, best way to give, and best dose of gamma-secretase inhibitor RO4929097 in treating patients with metastatic or unresectable solid malignancies. Enzyme inhibitors, such as gamma-secretase inhibitor RO4929097, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Safety profile of six different administration schedules of RO4929097

  Up to 4 weeks

Secondary Outcomes (3)

• Determination of pharmacokinetic profiles of various administration schedules

  Up to 4 weeks

• Preliminary antitumor activity of RO4929097 assessed using RECIST 1.1 criteria

  Up to 4 weeks

• Pharmacokinetic (PK) parameters of RO4929097 administered using six different dosing schedules

  Up to 4 weeks

Study Arms (6)

Group A

EXPERIMENTAL

Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3 and 8-10. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Group B

EXPERIMENTAL

Patients receive oral RO4929097 once daily on days 1-7. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Group C

EXPERIMENTAL

Patients receive oral RO4929097 once daily on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Group D

EXPERIMENTAL

Patients receive oral RO4929097 once daily on days 1, 8, and 15. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Group E

EXPERIMENTAL

Patients receive oral RO4929097 once daily on days 1, 4, 8, 11, 15, and 18. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Group F

EXPERIMENTAL

Patients receive oral RO4929097 once daily days 1-5, 8-12, and 15-19. Treatment in all groups repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies at baseline and between days 15 and 22 in the first course of treatment. Plasma samples are collected periodically for pharmacokinetic, pharmacodynamic, and pharmacogenomic analysis and to assess levels of adipsin and markers of angiogenesis.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Interventions

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Also known as: R4733, RO4929097

Group A; Group B; Group C; Group D; Group E; Group F

diagnostic laboratory biomarker analysis OTHER

Group A; Group B; Group C; Group D; Group E; Group F

pharmacogenomic studies OTHER

Also known as: Pharmacogenomic Study

Group A; Group B; Group C; Group D; Group E; Group F

pharmacological study OTHER

Also known as: pharmacological studies

Group A; Group B; Group C; Group D; Group E; Group F

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed solid malignancy
• Metastatic or unresectable disease
• Standard curative or palliative measures do not exist or are no longer effective
• 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 70-100%)
• Life expectancy \> 12 weeks
• Leukocytes ≥ 3,000/mm\^3
• ANC ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3
• Hemoglobin ≥ 9 g/dL
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal
• Serum creatinine normal OR creatinine clearance ≥ 60 mL/min
• No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as \< lower limit of normal despite adequate electrolyte supplementation

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

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

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; Pharmacogenomic Testing

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Lillian Siu

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2010
• First Posted: March 31, 2010
• Study Start: February 1, 2010
• Primary Completion: July 1, 2012
• Last Updated: April 2, 2014

Record last verified: 2013-12

Locations

CA (3)