| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Extensive Stage Disease Small Cell Lung Cancer (ED-SCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Small cell lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. |
|
| 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 | 10041068 |
| E.1.2 | Term | Small cell lung cancer extensive stage |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 compare overall survival (OS) of subjects randomized to ipilimumab
in addition to platinum and etoposide (Arm A) to that of subjects
randomized to placebo in addition to platinum and etoposide
(Arm B) in subjects with newly diagnosed extensive stage SCLC, among
subjects who received at least one dose of
blinded study therapy. |
|
| E.2.2 | Secondary objectives of the trial |
To compare OS of all randomized subjects between Arm A and Arm B
To compare Progression Free Survival (mWHO) in subjects who
received at least one dose of blinded study
therapy between Arm A and Arm B |
|
| 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 |
Protocol CA184156: Randomized, Multicenter, Double-Blind,
Phase 3 Trial Comparing the Efficacy of Ipilimumab Plus
Etoposide/Platinum versus Placebo plus Etoposide/Platinum in Subjects
with Newly Diagnosed Extensive-Stage Disease Small Cell Lung Cancer
(ED-SCLC)
Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific
Site All |
|
| E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
a) Willing and able to provide informed consent.
2) Target Population
a) Subjects with SCLC documented by histology or cytology from
brushing, washing or
needle aspiration of a defined lesion but not from sputum cytology alone.
b) Subjects must present with extensive stage disease (VALG
classification, and defined as
disease beyond ipsilateral hemithorax which may include malignant
pleural effusion or
pericardial effusion or hematogenous metastases)60,61.
c) Eastern Cooperative Oncology Group (ECOG) performance status 1.
d) Accessible for treatment and follow-up. Subjects enrolled in this trial
must be treated at
the participating centers.
e) Re-enrollment: permitted for a subject who has discontinued the
study as a pretreatment
failure (ie, subject has not been randomized / has not been treated). If
re-enrolled, the
subject must be re-consented.
3) Age and Reproductive Status
a) Men and Women 18 years of age.
b) Women of childbearing potential (WOCBP) must use method(s) of
contraception as
indicated in the Informed Consent Form. For a teratogenic study drug,
and/or when there
is insufficient information to assess teratogenicity (preclinical studies
have not been
done), a highly effective method(s) of contraception (failure rate of less
than 1% per
year) is required. The individual methods of contraception and duration
should be
determined in consultation with the investigator. WOCBP must agree to
follow
instructions for method(s) of contraception for the duration of treatment
with blinded
study drug plus 5 half-lives (75 days) plus 30 days (duration of
ovulatory cycle) for a
total of 105 days post completion of blinded study therapy.
c) Women must not be breastfeeding.
d) Sexually active fertile men must use effective birth control if their
partners are WOCBP.
Men that are sexually active with WOCBP must follow instructions for
birth control for
the entire duration of treatment with blinded study therapy, plus 5 halflives
of
ipilimumab (75 days) plus 90 days (duration of sperm turnover) for a
total of 165 days
post completion of blinded study therapy. |
|
| E.4 | Principal exclusion criteria |
1) Target Disease Exceptions
a) CNS metastases, unless non-symptomatic (ie, no neurological deficit, epilepsy or other signs and symptoms typical of CNS metastases), and not requiring treatment with steroids or anticonvulsant medications. In addition, if treated with radiation therapy, CNS metastases must be stable with no evidence of progression on scans for at least 30 days from initial radiologic diagnosis of CNS metastases.
b) Pleural effusion which cannot be controlled with appropriate interventions.
2) Medical History and Concurrent Diseases
a) Documented history of severe autoimmune or immune mediated symptomatic disease that required prolonged (more than 2 months) systemic immunosuppressive (ie, steroids) treatment such as: i) Ulcerative colitis and Crohn’s disease, ii) Rheumatoid arthritis, systemic progressive sclerosis (scleroderma),
iii) Systemic Lupus Erythematosus, iv) Autoimmune vasculitis (eg, Wegener’s Granulomatosis).
b) Subjects with history of motor neuropathy considered of autoimmune origin (eg, Guillain-Barré Syndrome).
c) Subjects with a history of toxic epidermal necrolysis (TEN).
d) Interstitial pneumonia or pulmonary fibrosis.
e) Paraneoplastic autoimmune syndrome
f) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing questionnaires.
g) Serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol therapy.
h) Prior malignancy, active within 5 years, except for locally curable cancers that have been apparently cured and need no subsequent therapy, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
i) HIV, active Hepatitis B, or active Hepatitis C infection, based on testing performed during the CA184156 screening period. In the event of a positive HIV or anti-HCV antibody test, results of confirmatory testing must be awaited before randomization.
j) Prior systemic therapy for lung cancer, including vaccines and other targeted therapies.
i) Prior radiation therapy or loco-regional surgeries are allowed.
k) Subjects with ≥ Grade 2 peripheral neuropathy.
3) Physical and Laboratory Test Findings
a) Inadequate hematologic function defined by:
i) Absolute neutrophil count (ANC) < 1,500/mm3, or
ii) Platelet count < 100,000/mm3; or
iii) Hemoglobin level < 9 g/dL.
b) Inadequate hepatic function as defined by either:
i) Total bilirubin level ≥ 2.5 times the ULN;
ii) AST and ALT levels ≥ 2.5 times the ULN or ≥ 5 times the ULN if liver metastases are present.
c) Inadequate renal function defined as calculated creatinine clearance < 50 ml/min based on the standard Cockroft and Gault formula.
d) Sodium (Na) < 130 mmol/l.
4) Prohibited Treatments and/or Therapies
a) Chronic use of immuno-suppressive drugs (ie, corticosteroids used in the
management of cancer or non-cancer related illnesses). Use of corticosteroids are allowed if used as premedication for chemotherapy administration or on-study management of an AE.
b) Any immunotherapy for the treatment of cancer.
c) Prior treatment with any inhibitor or agonist of T-cell co-stimulation.
5) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated.
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Overall survival (OS) in the population of randomized subjects who
received at least one dose of
blinded study therapy will be defined as the time from the date of
randomization until the date of
death. For those subjects who have not died, OS will be censored on the
last date the subject was
known to be alive. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assuming a monthly accrual rate of 5 subjects per month for the first 3
months, 10 subjects per month for the next
3 months, and 45 subjects per month thereafter, the total accrual will
take approximately 30 months. The number of
events is expected to occur 40.8 months after the first subject is
randomized. |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints are OS for all randomized subjects, and mWHO
PFS for randomized
subjects who received at least one dose of blinded study therapy. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 86 |
| 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 |
| Argentina |
| Australia |
| Austria |
| Belgium |
| Brazil |
| Canada |
| Chile |
| Colombia |
| Czech Republic |
| Finland |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Ireland |
| Israel |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Poland |
| Portugal |
| Romania |
| Russian Federation |
| Singapore |
| South Africa |
| Spain |
| Sweden |
| Switzerland |
| Taiwan |
| Thailand |
| United Kingdom |
| United States |
|
| 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
|
For all subjects, contact will be made every 12 weeks upon entry into the Overall Survival Follow-up Phase to evaluate Overall Survival and collect data on the initiation of subsequent therapy for the treatment of SCLC.
The final analysis of OS will be performed after 816 deaths, approximately 40.8 months after the first subject is randomized. Additional survival follow-up may occur after the final OS analysis to further characterize long-term survival for subjects randomized in this study. |
|
| 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 |
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