A RANDOMIZED, PHASE 3 STUDY OF GANETESPIB IN COMBINATION WITH DOCETAXEL VERSUS DOCETAXEL ALONE IN PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG ADENOCARCINOMA
This is an open-label, multicenter, randomized Phase 3 study (GaLaXY-2 TRiaL; Study
9090-14) of patients with advanced (Stage iiiB/iV) nSCLC of adenocarcinoma histology. eligible patients
must have failed only one prior platinum-based combination therapy for advanced nSCLC and have measurable
disease as defined by ReCiST criteria. This study will enroll 2nd-line patients diagnosed [GreaterThanorequalTo]6 months prior to study entry with advanced nSCLC and adenocarcinoma histology whose tumors are negative for both eGFR mutations and aLK translocations.
This study will enroll patients diagnosed [GreaterThanorequalTo]6 months prior to study entry with advanced nSCLC and adenocarcinoma histology whose tumors are negative for both eGFR mutations and aLK translocations.
Testing of tumor tissue for the presence of eGFR mutations and aLK translocations. Mutations in the eGFR gene will be evaluated by the cobas[RegisteredTM] eGFR Mutation Test. aLK translocations will be evaluated by Vysis[RegisteredTM] LSi aLK Break apart Fluorescence in situ hybridization (FiSH) Probe Kit. only patients whose tumors are negative for both eGFR mutations and aLK translocations may be enrolled. Testing must be performed by an accredited laboratory using these specified tests validated in that laboratory. Procedures for collection, handling, and testing of tissue samples are provided in the Study Manual. noTe: Tumor tissue collected at Screening from patients enrolled prior to amendment 2 that was not evaluated in an accredited laboratory using cobas and Vysis assays will be tested as described above.
Patients will be randomized in a 1:1 ratio to receive
either ganetespib in combination with docetaxel or docetaxel alone. The study will compare the
efficacy and tolerability of ganetespib in combination with docetaxel versus docetaxel alone.
The GaLaXY-2 TRiaLwill enroll approximately 850 patients diagnosed [GreaterThanorequalTo]6 months prior to study entry with advanced nSCLC and adenocarcinoma histology in order to obtain approximately 700 patients whose tumors are negative for both eGFR mutations and aLK translocations. Patients will be randomized into one of two treatment arms:
* arm a (control arm): Docetaxel 75 mg/m2 will be administered by 1-hour ((+-)10 minutes) intravenous (iV)
infusion on Day 1 of a 3-week treatment cycle
* arm B (combination arm): Ganetespib 150 mg/m2 in combination with docetaxel 75 mg/m2.
on Day 1 of each 3-week treatment cycle, ganetespib and docetaxel will be administered as
separate 1-hour ((+-)10 minutes) iV infusions. administration of ganetespib will precede the
administration of docetaxel. There will be a 1-hour [Quote]rest[Quote] period following the end of the
ganetespib infusion prior to docetaxel infusion. Ganetespib 150 mg/m2 will be administered
again on Day 15 of each cycle.
A patient is eligible for the study if all of the following criteria are met:
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 x 10^9/L
* Hemoglobin >=9 g/dL
* Platelets >=100 x 10^/L
11. Adequate hepatic function defined as:
* Albumin >=3 g/dL
* Serum total bilirubin <=1.5 x ULN
* AST and ALT <=1.5 x ULN without liver metastases; <=5 x ULN if documented liver metastases
12. Adequate renal function defined as:
* Serum creatinine <=1.5 x 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