A RANDOMIZED, PHASE 3 STUDY OF GANETESPIB IN COMBINATION WITH DOCETAXEL VERSUS DOCETAXEL ALONE IN PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG ADENOCARCINOMA

Phase 1

Conditions: 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 System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-004349-34-GB

Lead Sponsor: Synta Pharmaceuticals Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 696

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

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

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