E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extensive stage 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The trial aims to answer whether the addition of Ipilumimab to carboplatin and etoposide chemotherapy for patients with extensive stage small cell lung cancer is able to improve outcome for these patients as assessed by the proportion of patients alive and without progression at 1 year. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include assessment of the toxicity of the combination of ipilimumab together with carboplatin and etoposide chemotherapy and the tumour response to treatment. Disease free survival and overall survival of the trial population will also be assessed as well as quality of life. This will be measured using both standard written quality of life questionnaires and a novel electronic method of data collection using a mobile device carried by the patient for the duration of the trial. Immunological objectives of the trial will be to make a detailed assessment of the patients immune response to ipilimumab and to correlate this with clinical outcome data. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Willing and able to give written informed consent. • Histologic or cytological diagnosis of small cell lung cancer. • No active or chronic infection with HIV, Hepatitis B, or Hepatitis C. • Performance status ECOG 0 or 1, • Men and women, of or over 18 years of age. |
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E.4 | Principal exclusion criteria |
• Limited stage small cell lung cancer, appropriate for radical treatment with chemoradiation • Symptomatic CNS metastases (patients with asymptomatic CNS metastases – treated or untreated – may be included in the trial) • Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix. • Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn’s Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener’s Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis, Lambert Eaton Myasthenic syndrome). • Any underlying medical, neurological or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea. • Any live vaccine used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab). • Previous chemotherapy for small cell lung cancer, except for patients who have received up to two cycles of Carboplatin and Etoposide at comparible doses to those recommended in the protocol. These patients will be allowed to join the trial at cycle 2 or 3. • A history of prior treatment with ipilimumab, prior CD137 agonist or CTLA 4 inhibitor or agonist. • Concomitant therapy with any of the following: Interleukin 2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids. • Women of childbearing potential (WOCBP), as defined as below and who: • Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the duration of their participation in the study and for at least 8 weeks after cessation of study drug, or • Have a positive pregnancy test at baseline, or • Are pregnant or breastfeeding. • Sexually active WOCBP must use an effective method of birth control during the course of the study and for up to 26 weeks after last dose of ipilimumab, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP must have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as: Amenorrhea 12 consecutive months without another cause, or for women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level 35 mIU/mL. Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab. • Men of fathering potential must use an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1-year progression free survival. The proportion of patients alive and free from progression one year from consent. Tumour assessments will be by RECIST. |
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E.5.2 | Secondary end point(s) |
Progression free survival by RECIST; 1 year overall survival; overall survival; best overall response; duration of response; immune related progression free survival; immune related best overall response; immune related duration of response; toxicity assessment as defined by NCI CTCAE v4.0; quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression free survival by RECIST; 1 year overall survival; overall survival; best overall response; duration of response; immune related progression free survival; immune related best overall response; immune related duration of response; toxicity assessment as defined by NCI CTCAE v4.0; quality of life |
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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 | 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) | 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 | No |
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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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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The trial will end 100 days after the last dose of ipilimumab has been administered (ie when it is clear that the last dose has been given) or when all patients have died. |
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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 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |