A Randomized Discontinuation Phase II Trial of Deforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients with KRAS Mutations

Phase 1

• Conditions: on-small cell lung cancer; MedDRA version: 9.1 Level: LLT Classification code 10061873 Term: Non-small cell lung cancer

• Registration Number: EUCTR2008-005942-22-FR
• Lead Sponsor: Merck & Co. Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-03-18
• Study Completion: 2012-08-29
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 150

Inclusion Criteria

1.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 non-cytotoxic 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 method for the entire duration of the study, from the time of study enrollment until 30 days after the last dose of study drug.
a.Approved contraceptive methods include hormonal contraception, intra-uterine device, diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide (spermicides alone are not an acceptable method of contraception.)
b.WOCBP are defined as women who are not surgically sterile or who are not post-menopausal. Post-menopausal women who have been amenorrheic for less than one year are considered to be WOCBP unless they have a documented FSH value in the post-menopausal range.
10.Male partners of WOCBP agree to use approved methods of contraception for the entire duration of the study.
11.Patient must be available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.

Are the trial subjects under 18? no

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.
12.Patient has a requirement for concurrent treatment with medications that are strong inducers or inhibitors of cytochrome P450 (CYP3A) (see Appendix 6.2). Patients should be off these medications for at least 2 weeks prior to the first dose of deforolimus. Concomitant medications that are metabolized by CYP3A are allowed (e.g., simvastatin or atorvastatin).
13.Patient has newly diagnosed (within 3 months before enrollment) or poorly controlled Type 1 or 2 diabetes. Poorly controlled diabetes is defined as a fasting glucose >160 mg/dL during screening or being known to have a HbA1C > 8%.
14.Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study or interfere with the patient's participation for the full duration of the study, or it is not in the best interest of the patient to participate.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified