Non-Small Cell Lung Cancer (NSCLC) Patients with KRAS Mutations MedDRA version: 9.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS
Conditions
Interventions
Product Name: Deforolimus
Product Code: MK8669
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: deforolimus
CAS Number: 572924-54-0
Current Sponsor code: MK8669
Concentration unit: m
Sponsors
MERCK & CO., INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient has histologically confirmed stage IIIB/IV non-small cell lung cancer. 2. Patient has a documented mutation of the KRAS gene in tumor tissue. a. Patients with a known KRAS mutation must have documentation in the source documents, and are strongly encouraged to submit archival tissue material for central confirmation of mutation status. b. Patients without a previously documented mutation in the KRAS gene must submit a paraffin block or unstained slides for mutation testing and only those patients who test positive for a KRAS mutation will be eligible (see Study Operations Manual). 3. Patient has measurable disease by protocol-specific RECIST criteria (see the IIOM). 4. Patient has evidence of disease progression following 2 prior chemotherapy regimens, one of which was a platinum doublet. No more than 2 prior chemotherapy regimens for treatment of locally advanced or metastatic disease are allowed. Adjuvant (or neoadjuvant) chemotherapy given less than one year before disease recurrence is considered a prior chemotherapy regimen, but one additional prior cytotoxic chemotherapy regimen is allowed if it was given as adjuvant or neoadjuvant therapy more than one year before recurrence or progression to advanced disease. a. A prior chemotherapy regimen is defined as a drug regimen used for treatment of lung cancer that contains at least one conventional cytotoxic chemotherapy agent. b. Prior kinase inhibitor therapy and prior monoclonal antibody therapy are allowed, alone or in combination with chemotherapy. There is no limit on prior noncytotoxic agents or regimens. 5. A minimum of 4 weeks has elapsed between prior chemotherapy and day 1 of study treatment. A minimum of 14 days has elapsed since prior kinase inhibitor therapy or radiotherapy, and a minimum of 6 weeks has elapsed since prior monoclonal antibody therapy (e.g. cetuximab or bevacizumab). 6. Patient has performance status ≤2 on ECOG Performance Scale (Appendix, 6.1). 7. Patient voluntarily agreed to participate by giving written informed consent. 8. Patient is ≥18 years of age on day of signing informed consent. 9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to start of therapy and must use an approved contraceptive 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
Exclusion criteria: 1. Patient is known to have active brain metastases. Patients with previously treated brain metastases that are stable for > 3 months are eligible if a current brain MRI (within 28 days of day 1 of study treatment) shows no edema or evidence of progression compared to a prior study at least 3 months ago. 2. Patient is currently participating or has participated in a study with an investigational compound in or device within 30 days or 5 half lives of the investigational compound (which ever is greater) of initial dosing with study drug. 3. Patient has previously received rapamycin or rapamycin analogs, including deforolimus, everolimus, or temsirolimus. 4. Patient is receiving corticosteroids administered at doses greater than those used for normal replacement therapy. 5. Patient has a history of prior malignancy except for basal cell carcinoma of the skin, carcinoma in situ of the cervix; or any patient who has undergone potentially curative therapy for malignancy with no evidence of that disease for five years or who is deemed at low risk for recurrence by his treating physician. 6. Patient has known severe hypersensitivity to macrolide antibiotics (ie: clarithomycin, erythromycin, or azythromycin). 7. Patient has NYHA Class III or IV congestive heart failure or any other significant history of cardiac disease including: myocardial infarction within the last 6 months; ventricular arrhythmia or acute congestive heart failure within the last 3 months; uncontrolled angina or uncontrolled hypertension. 8. Patient is known to be HIV positive or has a known history of Hepatitis B or C. 9. Patient has a psychiatric disorder that would interfere with cooperation with the requirements of the trial, is a regular user of illicit drugs (including ``recreational use``), or has a recent history (within the last year) of drug or alcohol dependence. 10. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study. 11. Patient has an active infection requiring prescribed intervention.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of deforolimus in patients with KRAS mutant NSCLC who have progressed after two prior chemotherapy regimens compared to placebo by progression free survival analysis of randomized patients who have stable disease after an 8-week lead-in treatment with deforolimus.;Secondary Objective: chemotherapy regimens, to: Evaluate the safety profile of deforolimus. Evaluate the best overall response rate. Evaluate the overall duration of progression-free survival. Estimate overall survival. Estimate whether continuing therapy with deforolimus improves survival in patients who have experienced stable disease after 8 weeks of therapy with deforolimus.;Primary end point(s): The primary study endpoint is progression free survival (PFS) measured from the time of randomization. | — |
Countries
France, Germany, Italy, Spain
Outcome results
None listed