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 systemic therapy for advanced nSCLC disease and have measurable
disease as defined by ReCiST criteria. 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 500 patients over a planned 12-month period,
and patients will be randomized into one of two treatment arms:
* arm a (control arm): Docetaxel 75 mg/m2 will be administered by 1-hour 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 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.
The study will be divided into the following phases:
* Screening Phase x Screening assessments must occur within 4 weeks of randomization for
determination of patient's overall eligibility. These assessments will include medical history,
physical examination, tissue collection, determination of LDH levels and LDH isoforms, vital signs, electrocardiogram (eCG), eCoG PS, hematology and clinical chemistry serum human chorionic gonadotropin
pregnancy test (for all patients of child-bearing potential), radiological assessments of the
disease status, demographic information, record of concomitant medication, and record of
* Randomization Phase x Randomization will occur after patient's eligibility evaluation is completed.
* Treatment and Ganetespib Maintenance Phase x The first dose of study drug (ganetespib or docetaxel) will be
administered within 3 days of randomization.
in arm a, docetaxel will be administered according to prevailing practice and investigator decision, generally until disease progression, intolerability, or patient's withdrawal of consent. Crossover to treatment with ganetespib in combination with docetaxel or single-agent ganetespib maintenance therapy will not be permitted.
in arm B, the combination arm, patients will be treated with ganetespib in combination with
docetaxel. Docetaxel will be given according to prevailing practice and investigator decision,
generally until disease progression, unacceptable toxicity, or patient's withdrawal of consent.
Following completion of docetaxel treatment, patients whose disease has not progressed will
continue to receive ganetespib alone. This ganetespib maintenance therapy will continue until
one of the following occurs: disease progression, unacceptable toxicity, or patient's withdrawal
Treatment may be continued post disease progression in either arm (docetaxel in arm a, ganetespib in combination with docetaxel or ganetespib monotherapy in arm B) if the treating physician believes further treatment would provide clinical benefit.
* Follow-up Phase x after disease progression, patients will be followed for survival at approximately 6-week intervals
A patient is eligible for the study if all of the following criteria are met:
1. Age 18 years or older
2. Histologically confirmed diagnosis of NSCLC, with predominantly adenocarcinoma histology. (see appendix 1 in protocol)
3. Advanced (Stage IIIB/IV) NSCLC
4. Only one 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 (see Appendix 4)
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