E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous Non Small Cell Lung Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Non Small Cell Lung Cancer |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer 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 |
To evaluate the overall survival (OS) of patients with advanced squamous cell lung cancer receiving the combination of gemcitabine/carboplatin either with or without BSI-201. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following in patients with advanced squamous cell lung cancer receiving gemcitabine/carboplatin either with or without BSI-201:
•Progression free survival (PFS)
•Time to progression (TTP)
•Objective response rate (ORR)
•Safety and tolerability of the treatment regimen
•Quality of life as measured by EORTC QLQ-30 and QLQ-LC13
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The objective of the study is to evaluate potential biomarkers for predicting treatment efficacy. Blood samples and tumor tissue will also be collected for DNA and/or genetic testing.
• Several biomarkers related to the mechanism of action of iniparib and DNA damage repair, will be evaluated in the original tumor biopsy (if available) for possible correlation with clinical outcome. |
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E.3 | Principal inclusion criteria |
1. Newly diagnosed, stage IV squamous cell lung cancer. This includes patients who present with disseminated metastases, and those with a malignant pleural or pericardial effusion (i.e., formerly stage IIIB in the 6th TNM staging system).
2. Patients who have received prior adjuvant therapy for early-stage lung cancer are eligible if at least 12 months have elapsed from that treatment.
3. Histologically confirmed squamous cell bronchogenic carcinoma. Patients whose tumors contain mixed non-small cell histologies are eligible, as long as squamous carcinoma is
the predominant histology. Mixed tumors with small cell anaplastic elements are not eligible. Cytologic specimens obtained by brushings, washings, or needle aspiration of
the defined lesion are acceptable.
4. Patients with previous radiotherapy as definitive therapy for locally advanced non-small cell lung cancer are eligible, as long as the recurrence is outside the original radiation
therapy port. Radiation therapy must have been completed >4 weeks prior to the
initiation of study treatment. Patients who have received chemo/radiation for locally advanced NSCLC are not eligible. Patients who have received palliative radiation therapy for symptomatic metastases must have completed treatment >14 days prior the initiation of the study treatment.
5. Presence of evaluable (measureable or non-measurable) disease.
6. ECOG Performance Status of 0 or 1.
7. Laboratory values as follows:
- Absolute neutrophil count (ANC) >1,500/microL and platelets >100,000/microL (≤72 hours prior to initial treatment).
- Hemoglobin >9 g/dL (Note: Patients may be transfused or receive erythropoietin to maintain or exceed this level).
- Bilirubin < ULN.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement.
- Creatinine <2.0 mg/dL, or creatinine clearance >40 mL/min (as calculated by the Cockcroft-Gault method.
8. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with
partners of childbearing potential must use effective birth control measures during treatment and at least 6 months after the last dose of the study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Sexually active men must agree to use a medically acceptable form of birth control during treatment and at least 6 months after the last dose. If a female partner becomes pregnant during course of study the treating physician should be informed immediately.
9. >18 years of age.
10. Ability to understand the nature of this study, give written informed consent, and comply with study requirements.
11. Patients entering this study must be willing to provide tissue from a previous tumor biopsy (if available) for correlative testing. An exception to this is when the
national/local regulations prohibits some of the key activities of this research like the export of samples to third countries, storage of coded samples or global gene expression profiling without a pre-specified list of target genes. If tissue is not available, a patient will still be eligible for enrollment into the study. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with gemcitabine, carboplatin (except in the adjuvant setting), or Iniparib.
2. Past or current history of neoplasm other than the entry diagnosis, with the exception of treated non-melanoma skin cancer or carcinoma in-situ of any primary site, or invasive
cancers treated definitively, with treatment ending >5 years previously and no evidence of recurrences.
3. A history of cardiac disease, as defined by:
- Malignant hypertension
- Unstable angina
-Congestive heart failure
-Myocardial infarction within the previous 6 months
-Symptomatic, unstable or uncontrolled, cardiac arrhythmias. Patients who have stable, rate-controlled atrial fibrillation are eligible for study enrollment.
4. Active brain metastases. Patients with treated brain metastases are eligible, if (1) radiation therapy was completed at least 2 weeks prior to study entry; (2) follow-up scan shows no disease progression; and (3) patient does not require steroids.
5. Women who are pregnant or lactating.
6. Any serious, active infection (> Grade 2) at the time of treatment.
7. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
8. A major surgical procedure, or significant traumatic injury ≤28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
9. Uncontrolled or intercurrent illness including, that in the opinion of the investigator may increase the risks associated with study participation or administration of the
investigational products, or that may interfere with the interpretation of the results.
10. History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with the study participation or administration of the investigational products, or that may interfere with the interpretation of the results.
11. Known or suspected allergy/hypersensitivity to any agent given in the course of this trial.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary objectives of this study are to evaluate the following in patients with stage IV
squamous NSCLC receiving gemcitabine/carboplatin either with or without iniparib:
• Progression free survival (PFS)
• Time to progression (TTP)
• Objective response rate (ORR)
• Safety and tolerability of the treatment regimen
• Quality of life as measured by EORTC QLQ-30 and QLQ-LC13 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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) | 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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Canada |
Israel |
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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All patients will be followed for safety for a minimum of 30 days following the last administration of study drug.
Follow-up visits will be performed at least up to the final analysis cut-off date (date when
561 deaths are reached). Further follow–up of the patients who are alive at the time of the final
analysis cut-off date may be performed for a survival update for up to 2 years. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |