E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ADVANCED NON-SMALL-CELL LUNG ADENOCARCINOMA |
|
E.1.1.1 | Medical condition in easily understood language |
ADVANCED NON-SMALL-CELL LUNG CANCER |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025038 |
E.1.2 | Term | Lung adenocarcinoma stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025037 |
E.1.2 | Term | Lung adenocarcinoma stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Compare OS in NSCLC patients with adenocarcinoma histology treated
with ganetespib in combination with docetaxel versus docetaxel alone |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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
measurements. QTcF (Fridericia's formula) is preferred.
viii. Serum potassium, magnesium, or calcium levels outside the
laboratory's reference range
12. Uncontrolled intercurrent illness including, but not limited to,
patients receiving combination antiretroviral therapy or patients with
severe or systemic infection, or psychiatric illness/social situations that
would limit compliance with study
requirements.
13. Other severe acute/chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or study drug administration, or may interfere with the
interpretation of study results, and in the judgment of the Investigator
would make the patient inappropriate for entry into this study.
NOTE: Patients with a history, or at a risk, of pulmonary embolism are
eligible with appropriate use of anti-coagulant therapy.
NOTE: Patients cannot receive other investigational treatments while on
treatment in this study. If a patient has participated in an interventional
clinical trial, a minimum of 30 days or 5 half-lives must elapse before
randomization into this study.
14. Women who are breastfeeding |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is OS. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final OS analysis will be performed when approximately 560 deaths have been observed |
|
E.5.2 | 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 |
|
E.5.2.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Ganetespib+docetaxel vs docetaxel alone |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 152 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Bosnia and Herzegovina |
Canada |
Croatia |
Czech Republic |
France |
Germany |
Hungary |
Poland |
Romania |
Russian Federation |
Serbia |
Slovenia |
Spain |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |