E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041067 |
E.1.2 | Term | Small cell lung cancer |
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 |
Overall response rate [ORR = CR + PR] |
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E.2.2 | Secondary objectives of the trial |
• TTP
• OS
• Toxicity
• Correlation between Response Rate (RR) and level of MGMT promoter methylation and/or BER genes alterations.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed SCLC with MGMT methylation.
2. Patient previously treated by one or two chemotherapy lines.
3. Age ≤ 75 and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
4. Patients must have measurable disease, defined as at least one lesion than can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20mm with conventional techniques or as >10mm with spiral CT scan.
5. Patient with controlled brain metastases are eligible.
6. Patient previously treated with chest and/or brain RT are eligible.
7. Life expectancy >3 months.
8. Patient must have normal organ and marrow function as defined below:
- leukocytes >3,000/μL
- absolute neutrophil count >1,000/μL
- platelets >100,000/μL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
- creatinine within normal institutional limits
9. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter.
10. Ability to understand and the willingness to sign a written informed consent document.
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E.4 | Principal exclusion criteria |
1. Histologically or cytologically confirmed SCLC without MGMT methylation.
2. Patients who have received three or more previous chemotherapy lines for small cell lung cancer or radiotherapy on target lesions.
3. Symptomatic uncontrolled CNS metastasis.
4. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
5. Presence of infection.
6. History or evidence of malabsorption syndrome or disease that may significantly affect gastrointestinal function.
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or other agents used in the study.
8. Presence of medical problems of sufficient severity to prevent full compliance with the study.
9. Other known malignant neoplastic diseases in the patient’s medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the overall response rate [ORR = CR + PR] according to RECIST 1.1 criteria. |
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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) |
Secondary end points are Time to Progression (TTP), Toxicity, Overall Survival (OS), the correlation between Response Rate (RR) and level of MGMT promoter methylation and/or BER genes alterations. |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Correlation between Response Rate (RR) and level of MGMT promoter methylation and/or BER genes alterations. |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |