ADVANCED NON-SMALL-CELL LUNG ADENOCARCINOMA MedDRA version: 18.1 Level: PT Classification code 10025038 Term: Lung adenocarcinoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: PT Classification code 10025037 Term: Lung adenocarcinoma stage III Sys
Conditions
Sponsors
Synta Pharmaceuticals Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older 2. Pathologically confirmed diagnosis of NSCLC, with predominantly adenocarcinoma histology. Tumors must be negative for both EGFR mutations and ALK translocations. 3. Advanced (Stage IIIB/IV) NSCLC 4. Only 1 prior systemic therapy for advanced disease defined as a platinum-based combination chemotherapy NOTE: Prior neoadjuvant or adjuvant therapy for completely resected Stage I, II, or IIIA disease is allowed. NOTE: Maintenance therapy with approved, standard-of-care drugs (eg, pemetrexed, bevacizumab) is allowed provided that it was started no more than 6 weeks after the last dose of prior cancer therapy and there was no evidence of disease progression. 5. Diagnosis of advanced NSCLC =6 months prior to signing of informed consent document 6. Documented disease progression during or following first-line therapy for advanced disease 7. Measurable disease 8. Available archived tumor tissue block with sufficient tumor tissue for biomarker testing; alternatively unstained slides with sufficient tumor tissue may be substituted. If archived tissue is not available, a fresh biopsy will be obtained during the screening period. 9. ECOG PS 0 or 1 NOTE: With PS 1 on ECOG scale, patients must be scored =80 on Karnofsky Performance Status (KPS) scale 10. Adequate hematologic function defined as: • Absolute neutrophil count (ANC) =1.5 × 10^9/L • Hemoglobin =9 g/dL • Platelets =100 × 10^9/L 11. Adequate hepatic function defined as: • Albumin =3 g/dL • Serum total bilirubin =1.5 × ULN • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =1.5 × ULN without liver metastases; =5 × ULN if documented liver metastases 12. Adequate renal function defined as: • Serum creatinine =1.5 × ULN or calculated creatinine clearance (cCrCl) per Cockcroft-Gault formula = 50mL/min 13. Negative serum human chorionic gonadotropin pregnancy test at study entry for patients of childbearing potential. Patients of reproductive potential must agree to use adequate contraception for the duration of study treatment and for 30 days after the last dose of ganetespib, and for 3 months (women) and 6 months (men) after the last dose of docetaxel since docetaxel can have genotoxic effects and may alter male fertility. 14. Ability to understand, and willingness to sign, a written informed consent document and to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures 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 600 F.1.3 Elderly (>=65 years)
Exclusion criteria
Exclusion criteria: 1. Predominantly squamous, adenosquamous histology, or unclear histologic type 2. Prior maintenance therapy with an investigational anticancer agent 3. Prior treatment with tyrosine kinase inhibitors (TKIs) for lung cancer. 4. Patients with tumors known to harbor molecular alterations for which a targeted therapy is approved. NOTE: Patients whose tumors have not been tested for molecular alterations for which a targeted therapy is approved are not eligible. 5. Presence or suspicion of central nervous system (CNS) metastases and/or leptomeningeal carcinomatosis as determined by magnetic resonance imaging/computed tomography (MRI/CT) scan performed at screening. NOTE: Patients who have stable CNS metastases for at least 2 weeks following completion of radiotherapy are eligible 6. Active malignancies other than NSCLC within the last 5 years except for adequately treated in situ carcinoma of the cervix uteri, or basal or squamous cell carcinoma of the skin 7. Significant weight loss defined as =10% body weight within the 4 weeks prior to randomization 8. History of pulmonary hemorrhage or hemoptysis National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) =Grade 2 within 4 months of randomization 9. Peripheral neuropathy NCI CTCAE =Grade 2 at baseline 10. Patients with only 1 measurable lesion that was exposed to prior radiotherapy; the exception is lesions with documented disease progression with new tissue growth of at least 1 cm in longest diameter compared to nadir scan. NOTE: Patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of first dose of study drug 11. Known serious cardiac illness or medical conditions, including but not limited to: i. Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker ii. Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (eg, sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted. iii. Use of medications that have been linked to the occurrence of torsades de pointes iv. Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker v. Complete left bundle branch block (LBBB) vi. History of long QT Syndrome or a family member with this condition vii. QTc >470 ms (average of triplicate ECG recordings). A consistent method of QTc calculation must be used for each patient's QTc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare OS in NSCLC patients with adenocarcinoma histology treated with ganetespib in combination with docetaxel versus docetaxel alone ;Primary end point(s): The primary endpoint of the study is OS.;Timepoint(s) of evaluation of this end point: The final OS analysis will be performed when approximately 560 deaths have been observed; Secondary Objective: Key Secondary Objectives • Compare PFS between the 2 treatment arms • Compare OS between the 2 treatment arms in patients with elevated screening serum lactate dehydrogenase (eLDH) levels. Other Secondary Objectives • Compare ORR. DCR, and DOR between the 2 treatment arms • Compare PFS, ORR, and DCR between the 2 treatment arms in patients with screening serum eLDH levels. • Compare the emergence of metastatic lesions between the 2 treatment arms • Evaluate the safety of study treatments in this patient population • Compare patient quality of life as measured by the EQ-5D-3L test between the 2 treatment arms • Compare symptom improvement as measured by the FACT-L version 4 test between the 2 treatment arms • Assess the correlation between biomarkers, including KRAS status, and clinical outcome | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: OS in eLDH will be analyzed in a similar fashion as the primary efficacy analysis except the stratification variable for LDH will not be used in stratified analyses. - PFS, where progression assessed at the investigative site is the interval from the date of randomization until tumor progression - ORR is the proportion of patients who achieve tumor response (CR or PR) per modified RECIST 1.1. - DCR is defined as the proportion of patients with best response, according to modified RECIST 1.1, of CR, PR, or SD. - Duration of Response (DOR) is measured from the time measurement criteria are first met for CR/PR per modified RECIST 1.1 until the first date that recurrent or PD is objectively documented. ; Secondary end point(s): The key secondary endpoints for this study are the PFS for all randomized patients and OS for patients with eLDH. Other secondary endpoints: - ORR, DCR, Duration of Response (DOR), emergence of new metastatic lesions | — |
Countries
Austria, Belgium, Bosnia and Herzegovina, Canada, Croatia, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovenia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactMedical Officer
Synta Pharmaceuticals Corp.
Outcome results
None listed