A Randomized Discontinuation Phase II Trial of Ridaforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients With KRAS Mutations
- Conditions
- -C34 Malignant neoplasm of bronchus and lungMalignant neoplasm of bronchus and lungC34
- Registration Number
- PER-038-09
- Lead Sponsor
- MERCK SHARP & DOHME PERU S.R.L.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 0
• The patient has histologically confirmed stage IIIB / IV non-small cell lung cancer.
• The patient has a documented mutation of the KRAS gene in tumor tissue.
• The patient has a quantifiable disease according to the RECIST criteria specific to the protocol (see IIOM).
• The patient has evidence of disease progression after 2 previous chemotherapy regimens, one of which was a platinum double. No more than 2 previous chemotherapy regimens are allowed for the treatment of a locally advanced or metastatic disease. The adjuvant (or neoadjuvant) chemotherapy provided in less than one year before the recurrence of the disease is considered as a previous chemotherapy regimen, but an additional previous cytotoxic chemotherapy regimen is allowed if it was provided as an adjuvant or neoadjuvant therapy more than one year before the recurrence or evolution to an advanced disease.
• A minimum of 4 weeks has elapsed between previous chemotherapy and day 1 of the study treatment. A minimum of 14 days has elapsed since the previous therapy with a kinase inhibitor or radiotherapy, and a minimum of 6 weeks has elapsed since the previous therapy with a monoclonal antibody (for example, cetuximab or bevacizumab).
• The patient has a general status ^ on the General Status Scale according to the ECOG (Appendix, 6.1).
• The patient agreed to participate voluntarily by providing written informed consent.
• The patient is> 18 years of age on the day of signing the informed consent.
• Potentially fertile women (WOCBP) must have a negative serum pregnancy test within 7 days prior to the start of therapy and must use an approved contraceptive method throughout the study, from the time of study enrollment up to 30 days after the last dose of the study drug.
• WOCBP male partners agree to use approved contraceptive methods throughout the study.
• The patient should be available for periodic blood sampling, evaluations related to the study, and management at the treating institution throughout the study.
• The patient has an adequate organic function as indicated by laboratory values
• It is known that the patient has active brain metastases. Patients with previously treated brain metastases that are stable for> 3 months are eligible if a current MRI of the brain (within 28 days of day 1 of the study treatment) does not show edema or evidence of evolution compared to a study previous of at least 3 months ago.
• The patient is currently participating or has participated in a study with a compound or device under investigation within 30 days or 5 half-lives of the compound under investigation (whichever is greater) of the initial dose administration of the study drug .
• The patient has previously received rapamycin or rapamycin analogues, such as deforolimus, everolimus or temsirolimus.
• The patient is receiving administered corticosteroids
• The patient has a history of previous malignancy except for cutaneous basal cell carcinoma, carcinoma in situ of the cervix; or any patient who has undergone a potentially curative therapy for malignancy without evidence of said disease for five years, or who is considered by their attending physician to have a low risk of recurrence.
• The patient has known severe hypersensitivity to macrolide antibiotics (ie clarithromycin, erythromycin or azithromycin).
• The patient has Class III or IV congestive heart failure according to the NYHA or any other significant history of heart disease such as: myocardial infarction within the last 6 months; ventricular arrhythmia or acute congestive heart failure within the last 3 months; uncontrolled angina or uncontrolled hypertension.
• It is known that the patient is HIV positive or has a known history of Hepatitis B or C.
• The patient has a psychiatric disorder that could interfere with the cooperation with the test requirements, is a regular user (including recreational use) of illicit drugs, or has a recent history (within the last year) of Drug or alcohol dependence.
• The patient is pregnant or breastfeeding, or hopes to conceive within the projected duration of the study.
• The patient has an active infection that requires prescription intervention.
• The patient requires concurrent treatment with drugs that are strong inducers or inhibitors of cytochrome P450 (CYP3A) (see Appendix 6.2). Patients should not receive these drugs for a minimum of 2 weeks before the first dose of deforolimus. Concomitant drugs that are metabolized by CYP3A are allowed (for example, simvastatin or atorvastatin)
• The patient has recently diagnosed Type 1 or 2 diabetes (within 3 months prior to enrollment) or poorly controlled.
• The patient has a current history or evidence of any laboratory condition, therapy or abnormality that could confuse the results of the study or interfere with the patient´s participation throughout the study, or it is not convenient for the patient to participate.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Defined, in the randomized population, as the time from randomization to progressive disease or death, whichever is earlier. Patients without an event at the time of analysis will be censored at the date of the last tumor assessment.<br>Measure:Progression-free Survival (PFS) in the randomized population<br>Timepoints:Randomization (Week 8) and every 8 weeks until progressive disease or death<br>
- Secondary Outcome Measures
Name Time Method