A study to test a new drug for treating non-small cell lung cancer
- Conditions
- Advanced non-small cell lung cancer and BRAF mutationsMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001161-41-NL
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 166
Subjects eligible for enrolment in the study and previously enrolled subjects crossing over from monotherapy to combination therapy must meet all of the following criteria:
1. Signed written informed consent;
2. Histologically- or cytologically-confirmed diagnosis of NSCLC stage IV (according to AJCC Staging 7th Edition);
3. Documented tumor progression (based on radiological imaging) after receiving at least one prior approved platinum-based chemotherapy regimen for advanced stage/metastatic NSCLC. An alternate chemotherapeutic agent/regimen is an acceptable substitute in the event that the subject was intolerant to, or ineligible to receive platinum based chemotherapy. Subjects enrolled in Cohort B cannot have more than 3 prior systemic treatments for advanced stage/metastatic NSCLC (neoadjuvant and adjuvant therapies are not counted in number of prior regimens and maintenance therapy is not counted as a separate regimen). Subjects in Cohort C will be required to have not received prior systemic anti-cancer therapies for metastatic disease (i.e., dabrafenib/trametinib will be 1st line treatment for metastatic disease)
4. Measurable disease according to RECIST v1.1 [Eisenhauer, 2009]. Refer to Section 7.2.3.1 for the definition of a measurable lesion;
5. Male or female =18 years of age;
6. Anticipated life expectancy of at least 3 months;
7. Presence of a BRAF V600E mutation in lung cancer tissue. Mutation must be locally confirmed in a CLIA-certified laboratory (or equivalent). An adequate amount of umor tissue (archived tumor tissue, or fresh biopsy if archived tissue is not available) must be available at the time of enrolment for central validation of BRAF mutation see Section 7.1.1 for testing details and requirements regarding central confirmation);
8. Able to swallow and retain oral medication;
9. Women of childbearing potential must have a negative serum pregnancy test within 14 days before the first dose of study treatment and agree to use effective contraception, as defined in Section 7.4, during the study;
NOTE: Oral contraceptives are not reliable due to potential drug-drug interaction with dabrafenib
10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 [Oken, 1982];
11. Must have adequate baseline organ function as definedin Table 1:
Hematologica
ANC = 1.5 × 109/L
Hemoglobin = 9 g/dL
Platelet count = 100 x 109/L
PT/INRb and PTT = 1.3 x ULN
Hepatic
Total bilirubin = 1.5 x ULN
AST and ALT = 2.5 x ULN
Renal (at least one of the following):
Serum creatininec = 1.5 mg/dL
Creatinine clearancec = 50 mL/min
Cardiac
Left Ventricular Ejection fraction (LVEF)d = LLN by ECHO
12. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
13. Previously tested for presence of EGFR and ALK mutations in lung cancer tissue confirmed in a CLIA-certified laboratory (or equivalent). Subjects with EGFR or ALK mutation are eligible if they have previously received EGFR or ALK inhibitor(s) respectively.
Further protocol-defined inclusion criteria may apply
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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
Subjects eligible for enrolment in the study and previously enrolled subjects crossing over from monotherapy to combination therapy must not meet any of the following criteria:
1. Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, LGX818, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) prior to start of study treatment
(Note: Prior treatment with dabrafenib is allowed for crossover subjects in Cohort A);
2. Anti-Cancer therapy including chemotherapy, radiation-therapy, immunotherapy, biologic therapy or major surgery within 14 days prior to start of study treatment (Note: Dabrafenib monotherapy within 14 days prior to starting combination therapy
is allowed for crossover subjects in Cohort A);
3. Use of any investigational anti-cancer drug within 14 days or 5-half-lives (minimum 14 days), prior to start of study medication (Note: Dabrafenib monotherapy within 14 days prior to starting combination therapy is allowed for crossover subjects in Cohort
A);
4. Current use of a prohibited medication or expected to require any of thesemedications during treatment with study treatment (See Section 6.2);
5. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 or higher from previous anti-cancer therapy, except alopecia;
6. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GlaxoSmithKlne
(GSK) medical monitor for guidance to enrol the subject;
7. Known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection may be enrolled;
8. History of another malignancy < 3 years prior to starting study treatment or any malignancy with confirmed activating RAS-mutation;
Exceptions: subjects with any of the following malignancies within 3 years (does not include malignancies with confirmed activating RAS-mutation) are eligible: (a) a history of completely resected skin cancer, (b) successfully treated in situ carcinoma,
(c) chronic lymphocytic lymphoma (CLL) in stable remission, or (d) indolent prostate cancer (definition: clinical stage T1 or T2a, Gleason score =6, and prostate specific
antigen [PSA] < 10 ng/mL) requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from lung cancer target and non-target lesions are eligible
9. Subjects with brain metastases are excluded if their brain metastases are:
• Symptomatic OR
• Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy(as assessed by contrast enhanced magnetic resonance imaging [MRI] or computed tomography [CT]), OR
• Asymptomatic and untreated but >1 cm in the longest dimension
10. A history or evidence of cardiovascular risk including any of the following:
• Corrected QT (QTc) interval =480 msecs
• History of acute coronary syndromes (including myocardial infarction or unstable angina) within 6 months prior to first dose of study treatment
• Coronary angioplasty, or stenting within the past 24 weeks;
• A history or evidence of current Class II, III, or IV heart failure as defined by the New York Heart Associati
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method