A phase II study of orally administered RO4929097, a gamma-secretase inhibitor, as a single agent in patients with recurrent or refractory Non-Small Cell Lung Cancer (NSCLC).

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-006384-37-NL
• Date of registration: 20/07/2009
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A phase II study of orally administered RO4929097, a gamma-secretase inhibitor, as a single agent in patients with recurrent or refractory Non-Small Cell Lung Cancer (NSCLC).
• Scientific title: A phase II study of orally administered RO4929097, a gamma-secretase inhibitor, as a single agent in patients with recurrent or refractory Non-Small Cell Lung Cancer (NSCLC).
• Date of first enrolment: 06/10/2009
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006384-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent
2. Patient ability to comply with protocol requirements (visits and assessment schedules).
3. Stage IIIB/IV histologically-confirmed NSCLC that is recurrent or refractory to at most 2 lines of therapy for metastatic disease. Therapy is limited to:
• First line - platinum containing regimen - bevacizumab
• Second line - Single-agent EGFR targeted therapies. Acceptable agents include either smallmolecule tyrosine kinase inhibitors (i.e. gefitinib or erlotinib) or monoclonal antibodies. Acceptable agents include either smallmolecule tyrosine kinase inhibitors (i.e. gefitinib or erlotinib) or monoclonal antibodies.
Other therapies are not allowed.
4. Patients must have a measurable disease by contrast enhanced CT and detectable by PET scanning. Screening tumor evaluation should be performed within 7 days before the first study drug administration. The Investigator/designee with assess the PET and CT scans to confirm patient eligibility.
5. Adult patients aged =18 yrs.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
7. Adequate liver function: Total bilirubin = 1.5 mg/dL, AST and ALT = 2.5x institutional ULN (or = 5 x ULN if liver metastases present); alkaline phosphatase = 2.5x ULN (or = 5 x ULN if liver or bones metastases present).
8. Adequate renal function: serum creatinine = 1.5 mg/dL or creatinine clearance estimate = 45 mL/min (according to Cockroft-Gault formula)
9. Adequate bone marrow function, defined by: ANC = 1.5 x 10 exp9/L, platelets = 100 x 10 exp9/L, and hemoglobin = 8.5 g/dL. Patients should not require chronic supportive growth factor administration or transfusions to meet treatment eligibility criteria (e.g., G-CSF for ANC eligibility).
10. Women of child-bearing potential and women less than 2 years after menopause must have a negative urine pregnancy test result within 72 hours prior to the start of study drug administration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Treatment with any investigational agent within 28 days of first receipt of study drug.
2. Prior chemotherapy or radiotherapy within 4 weeks (other than a short cycle of palliative radiotherapy for bone pain) of first receipt of study treatment.
3. Patients unable to swallow oral medications or with preexisting GI disorders that might interfere with proper absorption of the oral drug.
4. History of other malignancy, either primary or recurrent, within the past 2 years, except basal cell skin carcinoma or in situ cervical carcinoma.
5. History of active seizure disorder (e.g. event = 2 months prior to start of study).
6. Patients with a history of CNS metastases or leptomeningeal metastases, except for those who have clinically stable disease characterized by all the following:
• surgical resection and/or radiotherapy completed = 2 months prior to first dosing.
• no corticosteroid requirements for CNS disease for = 4 weeks prior to first dosing.
• stable disease measured by CT or MRI within 4 weeks of first dosing.
• stable neurologic exam (no new global or focal abnormalities) for at least 4 weeks prior to first dosing.
To confirm eligibility, a discussion between the Investigator and Sponsor is required for patients with CNS disease.
7. Serious cardiovascular illness including but not confined to symptomatic CHF, unstable angina pectoris, symptomatic cardiac arrhythmia or cardiac pacemaker requirement.
8. QTcF > 450 msec (males) and QTcF > 470 msec (females) at screening.
9. Other uncontrollable, concurrent illness including, but not limited to: significant hypoxia requiring chronic oxygen therapy; active or uncontrolled infection, altered mental status or psychiatric illness that would limit compliance with study requirements.
10. Pregnant women and women who are breast feeding.
11. Unwillingness or inability to use acceptable (e.g. barrier) method of contraception during study and up to 4 weeks post last dose of study medication for non-sterile men and women of child-bearing potential and women less than 2 years after menopause.
12. Patients receiving CYP3A4 substrates, or inhibitors within 7 days prior to receipt of study drug and CYP3A4 inducers within 14 days prior receipt of study drug.
13. Major surgery within 28 days of first receipt of study drug.
14. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that in the opinion of the Investigator, contraindicates the use of an investigational drug, or that may render the patient at excessively high risk for treatment complications.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with recurrent or refractory stage IIIB/IV NSCLC.
MedDRA version: 9.1 Level: LLT Classification code 10029515 Term: Non-small cell lung cancer recurrent
MedDRA version: 9.1 Level: LLT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB
MedDRA version: 9.1 Level: LLT Classification code 10029522 Term: Non-small cell lung cancer stage IV

Intervention(s)

Product Name: gamma-secretase inhibitor
Product Code: RO4929097/F01
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not yet available
Current Sponsor code: RO4929097
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Product Name: gamma-secretase inhibitor
Product Code: RO4929097/F02
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not yet available
Current Sponsor code: RO4929097
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: gamma-secretase inhibitor
Product Code: RO4929097/F03
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not yet available
Current Sponsor code: RO4929097
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: To evaluate the effect of RO4929097 on tumor blood flow and tumor metabolic activity.

Secondary Objective: • To evaluate the effect of RO4929097 on defined pharmacodynamic (PD) parameters.
To evaluate the pharmacokinetic profile of RO4929097, assessed in the first two cycles of therapy.
• To characterize overall safety and tolerability of RO4929097 in this patient population
• To evaluate RO4929097 anti-tumor activity in this indication, assessed by Response rate (RECIST) and Time to tumor progression (TTP)
• To perform an exploratory analysis of both baseline response-predictive markers and PD markers.
Exploratory Objectives
The Roche Clinical Repository (RCR) will be used to:
• Study the association of biomarkers with efficacy and / or adverse events associated with medicinal products; and/ or
• Increase knowledge and understanding of disease biology; and/or
• Develop biomarker or diagnostic assays and/or establish the performance characteristics of these assays

Primary end point(s): The primary endpoint of this study is the assessment of changes in tumor blood flow and tumor metabolic response rate following treatment with RO4929097 (see section 8.1 in the protocol).

Secondary ID(s)

NP22383