E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025054 |
E.1.2 | Term | Lung cancer non-small cell stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025055 |
E.1.2 | Term | Lung cancer non-small cell stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Stage 1 Evaluate progression free survival (PFS) in subjects with stage IIIB or IV NSCLC treated with the combination of ganetespib and docetaxel compared to docetaxel alone.
Evaluate Overall Survival (OS) in subjects with high baseline serum levels of total LDH
Stage 2 Assess OS in subjects with stage IIIB or IV NSCLC treated with the combination of ganetespib and docetaxel compared to docetaxel alone |
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E.2.2 | Secondary objectives of the trial |
Stage 1 1. Compare the two treatment groups with respect to the following: overall response rate (ORR), clinical benefit rate (CBR), mean tumor size change, 1-year OS, and OS 2. Determine the qualitative and quantitative toxicities associated with ganetespib administered in combination with docetaxel 3. Determine the plasma drug concentrations at selected times of ganetespib and docetaxel in a subset of subjects 4. Evaluate quality of life (QOL) status within the study population and compare the impact on QOL between treatment groups, using EORTC QLQ -C30 questionnaire
Stage 2 1. Compare the two treatment groups with respect to the following: PFS, ORR, CBR, mean tumor size change and 1-year OS 2. Further characterize the safety of ganetespib in combination with docetaxel 3. Evaluate QOL status within the study population and compare the impact on QOL between treatment groups, using EORTC QLQ -C30 questionnaire |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects aged 18 years or older 2. Pathologically confirmed diagnosis of NSCLC 3. Stage IIIB or IV NSCLC 4. ECOG Performance Status 0 or 1 5. Prior therapy defined as: • One prior systemic therapy for advanced disease that includes: i. A platinum-based chemotherapy; or ii. EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated disease • NOTE: Approved maintenance therapy (e.g., pemetrexed) is allowed provided that it was started no more than 4 weeks after the last dose of prior therapy for advanced disease. Prior adjuvant or neoadjuvant therapy for early stage disease is allowed • NOTE: Previous anticancer treatment must have stopped at least 2 weeks prior to randomization 6. Measurable disease by modified RECIST 1.1 7. Radiologic evidence of disease progression following most recent prior treatment. Disease progression is defined as: • Appearance of any new lesion or an increase of ≥ 20% of one or more existing lesions. Radiological scans from the subject’s most recent treatment must document the baseline or lowest tumor burden (nadir scans) and disease progression 8. Subjects with CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable and the subject has been off steroids after appropriate therapy for at least 3 months prior to randomization 9. Adequate hematologic function defined as: • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L • Hemoglobin ≥ 9 g/dL • Platelets ≥ 100 × 109/L 10. Adequate hepatic function defined as: • Albumin ≥3 g/dL • Serum total bilirubin ≤1.5 x ULN • AST and ALT ≤1.5 × ULN without liver metastases; ≤5 × ULN if documented liver metastases 11. Adequate renal function defined as • Serum Creatinine ≤1.5 mg/dL or calculated creatinine clearance (CLcr) per Cockgroft- Gault formula ≥ 60mL/min 12. Negative serum pregnancy test at study entry for female subjects of childbearing potential 13. Female subjects of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and for 30 days after the last dose of study drug. 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 |
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E.4 | Principal exclusion criteria |
1. Presence of active or untreated CNS metastases as determined by MRI or CT scan performed during screening. 2. Active malignancies other than NSCLC within the last 5 years with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin 3. Serious cardiac illness or medical conditions including but not confined to: • History of documented congestive heart failure (CHF), New York Heart Association class II/III/IV, with a history of dyspnea, orthopnea or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics. NOTE: Use of these medications for the treatment of hypertension is allowed • Baseline QTc > 470 msec or history of QT prolongation while taking other medications • Left ventricular ejection fraction (LVEF) < 50 % at baseline • High-risk uncontrolled arrhythmias (ventricular tachycardia, high-Grade AV-block, supra-ventricular arrhythmias which are not adequately rate-controlled) that require current treatment with the following anti-arrythmic drugs: flecainide, moricizine or propafenone • Current coronary artery disease with a history of myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery Radiotherapy within 2 weeks prior to randomization (related toxicities must be ≤Grade 1) 5. Prior radiotherapy to the only area of measurable disease 6. Major surgery (unrelated to NSCLC) within 4 weeks prior to randomization 7. Hemoptysis ≥ Grade 2 at randomization 8. Peripheral neuropathy ≥ Grade 2 at randomization 9. History of severe allergic or hypersensitivity reactions to docetaxel or excipients (eg, polyethylene glycol [PEG] 300 and polysorbate 80) 10. Women who are pregnant or lactating 11. Significant weight loss of ≥ 10% body weight within the 4 weeks prior to randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
Stage 1 The primary endpoints of the study are (1) PFS and (2) OS in a subset of subjects with high baseline serum LDH.
Stage 2 Evaluation of OS in the two treatment arms |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Stage 1 An administrative interim analysis of PFS for Stage 1 is planned when approximately 70% of events have occurred.The primary analysis of PFS for Stage 1 will be conducted when approximately 191 PFS events have been observed. The primary analysis of OS in subjects with high baseline LDH will be conducted when approximately 73 OS events have occurred.
Stage 2 A formal interim OS analysis is planned when approximately 125 OS events (approximately 40% of the total number of deaths) have been observed. The primary analysis for median OS will be conducted when approximately 311 OS events have been observed. |
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E.5.2 | Secondary end point(s) |
Stage 1 Overall Response Rate, Clinical Benefit Rate, Mean tumour size changes, and 1 year overall survival and overall survival between the 2 treatment groups. Stage 2 Progression Free Survival, Overall Response Rate, Clinical Benefit Rate, Mean tumour size changes, and 1 year overall survival and overall survival between the 2 treatment groups
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Stage 1 and Stage 2 Mean tumor size changes from baseline to at least 6 and 12 weeks Clinical benefit is calculated by combining the rates of subjects with a best overall response of confirmed CR, PR and SD for at least 6 or 12 weeks, per modified RECIST 1.1
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
IMP as an add-on to standard of care treatment |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Belgium |
Bosnia and Herzegovina |
Canada |
Croatia |
Czech Republic |
Germany |
Hungary |
Netherlands |
Poland |
Romania |
Russian Federation |
Serbia |
Spain |
Ukraine |
United Kingdom |
United States |
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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
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End of trial is last survival follow-up which is approx 6 to 12 months after last patients' last visit
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |