E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of metastatic or unresectable non small cell lung cancer (NSCLC) with CS 1008 or placebo first in combination with carboplatin/paclitaxel then as monotherapy in the first line setting |
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E.1.1.1 | Medical condition in easily understood language |
Non-small cell lung cancer (NSCLC) is a general term for the most
common form of solid cancer which affects the lungs. |
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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 | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
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 | 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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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 determine the difference in progression free survival (PFS) in previously chemotherapy naïve subjects with stage IIIB wet or stage IV NSCLC treated with CS 1008 plus carboplatin/paclitaxel versus subjects treated with placebo plus carboplatin/paclitaxel. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of CS 1008 plus carboplatin/paclitaxel;
To evaluate the difference between the two treatment regimens CS-1008 plus carboplatin/paclitaxel and placebo (sodium Chloride) plus carboplatin/paclitaxel with respect to:
- Overall survival (OS);
- Objective response rate (ORR);
- Duration of response;
To determine the safety and tolerability of CS-1008 administered in combination with carboplatin/paclitaxel to previously chemotherapy naïve subjects with stage IIIB wet or stage IV NSCLC.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed, stage IIIB wet or stage IV NSCLC.
2. At least 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) criteria.
5. Adequate organ and bone marrow function as evidenced by:
- Hemoglobin >/= 9 g/dL;
- Absolute neutrophil count >/= 1.5 x 10(e +9)/L;
- Platelet count >/= 100 x 10(e +9)/L;
- Serum creatinine < 1.5 mg/dL or creatinine clearance > 60 mL/min;
- AST, ALT, and alkaline phosphatase </= 2.5 x upper limit of normal (ULN) if without liver metastasis and </
= 5.0 x ULN if liver or bone metastasis;
- Total bilirubin </= 1.5 x ULN.
6. Women of childbearing potential and men must be willing to consent to using highly effective methods of
contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device)
while on treatment and for at least 3 months thereafter.
7. Males with the potential to father children and women of childbearing potential must use two of the following
methods of contraception acceptable for the study (eg, hormonal contraceptives, bilateral tubal ligation, barrier
with spermicide, intrauterine device) while on trial treatment and for at least 3 months thereafter.
8. All female subjects of childbearing potential must have a negative pregnancy test (serum or urine) result ≤ 72
hours before initiating study treatment.
9. Subjects must be fully informed about their illness and the investigational nature of the study protocol
(including foreseeable risks and possible side effects) and must sign and date an independent ethics committee
(IEC)-approved informed consent
form (ICF) before performance of any study-specific procedures or tests.
10. Life expectancy of at least 12 weeks.
Note: symbol >/= is for greater or equal to.
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E.4 | Principal exclusion criteria |
1. Anticipation of need for a major surgical procedure or radiotherapy (RT) during the study for NSCLC.
2. No recurrent NSCLC or presence of clinically significant ascites.
3. Prior treatment with chemotherapy investigational medicinal products, or biological treatment for NSCLC.
4. Prior radiotherapy with curative intent for NSCLC.
5. Palliative radiotherapy for NSCLC within 4 weeks prior to first dose.
6. Major surgery within 4 weeks prior to first dose.
7. History of any of the following conditions within 6 months before study enrolment: myocardial infarction;
New York Heart Association (NYHA) class II or higher severe/unstable angina pectoris; coronary/peripheral
artery bypass graft; NYHA class III or IV congestive heart failure; cerebrovascular accident or transient
ischemic attack, pulmonary embolism, or other clinically significant thromboembolic event; clinically significant
pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma); clinically significant
pulmonary edema or anasarca.
8. Clinically significant pleural or pericardial effusions.
9. Grade 2 or higher current peripheral neuropathy
10. Clinically active brain metastasis (ie, untreated, still requiring therapy with steroids or RT, or with progression
within 4 weeks after completion of RT); an uncontrolled seizure disorder; spinal cord compression; or
carcinomatous meningitis.
11. History of malignancy other than NSCLC, unless there is the expectation that the malignancy has been cured,
and tumor-specific treatment for the malignancy has not been administered within the previous 5 years.
12. Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus
(HIV)-positive subjects receiving antiretroviral therapy.
13. Previous treatment with CS-1008, other agonistic DR 5 or DR 4 antibodies, or with TRAIL.
14. Pregnant or breast feeding.
15. Known history of hypersensitivity reactions to any of the components of CS-1008, carboplatin, or paclitaxel
formulations.
16. Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the
Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or
safety of the study treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the difference in PFS in previously chemotherapy naïve subjects with stage IIIB wet or stage IV NSCLC treated with CS-1008 plus carboplatin/paclitaxel versus subjects treated with placebo plus carboplatin/paclitaxel.
Additional exploratory assessments may include protein expression and genotype/gene expression of critical genes related to NSCLC or its treatment, possibly including but not limited to DR5, Bax, Bcl-x, cIAP, GALNT-14, and Mcl-1, in available archived tumour samples. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS data would be considered mature at 10 months after the last subject is randomised, or when 85 PFS events will have occurred, whichever is earlier. |
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E.5.2 | Secondary end point(s) |
As per the protocol:
• To evaluate the difference between the two treatment regimens CS-1008 plus carboplatin/paclitaxel and placebo plus carboplatin/paclitaxel with respect to:
• Overall survival (OS);
• Objective response rate (ORR);
• Duration of response;
• To determine the safety and tolerability of CS-1008 administered in combination with carboplatin/paclitaxel to previously chemotherapy naïve subjects with stage IIIB wet or stage IV NSCLC.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
It is projected that OS data will become mature when all subjects will have either died or been lost to follow-up, or at 24 months after the last subject is randomised, whichever is earlier. The actual final analysis date will depend on the study information. |
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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 | No |
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 | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker, protein and gene expression analysis |
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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) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 15 |