| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Stage IV/Recurrent Non-Small Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Progressed/Recurrent Lung Cancer |
|
| 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 | 18.0 |
| 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) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029515 |
| E.1.2 | Term | Non-small cell lung cancer recurrent |
| 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 with Stage IV/recurrent NSCLC of squamous histology who have been randomized to ipilimumab in addition to aclitaxel and carboplatin versus placebo in addition to paclitaxel and carboplatin. |
|
| E.2.2 | Secondary objectives of the trial |
| To compare Overall Survival in all randomized subjects who received at least one dose of blinded study therapy (OS2), Progression-Free survival (PFS) per mWHO and Best Overall Response Rate (BORR) per mWHO between the two treatment arms |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
a) Willing and able to provide informed consent
2) Target Population
a) Subjects with NSCLC of predominantly squamous histology 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 Stage IV or Recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer (IASLC) classification)
c) At least 1 measurable tumor lesion, as defined by mWHO criteria (section 5.4.2.2)
d) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 at study entry
e) Accessible for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating centers
f) 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 reconsented
3) Age and Reproductive Status
a) Men and Women ≥ 18 years of age
Women of childbearing potential (WOCBP) and their partners must be using highly effective method of birth control (double barrier, eg. condom or diaphragm or cervical cap associated with spermicide or intrauterine device combined with another form of birth control) for up to 8 weeks after the last dose of ipilimumab to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 12 weeks after dosing has been completed. See Section 3.3.3 for the definition of WOCBP
b) WOCBP must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) at screening and within 24 hours prior to the start of investigational product
c) Women must not be breastfeedingd) Women must not be breastfeeding |
|
| E.4 | Principal exclusion criteria |
1) Target Disease Exceptions
a) History of or current brain metastases
b) Pleural effusion that cannot be controlled despite 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) Dementia, altered mental status, or any psychiatric condition that would prohibit
the understanding or rendering of informed consent or completing questionnaires
e) Serious uncontrolled medical disorder that, in the opinion of the investigator,
would impair the ability of the subject to receive protocol therapy
f) 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
g) HIV positive or active Hepatitis B or active Hepatitis C infection based
on testing done during the screening period
h) Prior systemic therapy for locally advanced or metastatic lung cancer
including vaccines and other targeted therapies
- Prior radiation therapy or loco-regional surgeries are allowed
- Adjuvant/neo-adjuvant systemic therapy for lung cancer is allowed if
completed at least 1 year prior to enrollment in this study
i) Subjects with ≥ Grade 2 peripheral neuropathy
j) History of allergy or hypersensitivity to any component of the
treatment
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 upper limit of normal (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
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 non-oncology vaccine therapy used for prevention of infectious disease (for up to 4 weeks prior to or after any dose of blinded study drug)
c) Any immunotherapy for the treatment of cancer
d) Prior treatment with any inhibitor or agonist of T-cell co-stimulation
5) Sex and Reproductive Status
a) Sexually active fertile men not using effective birth control if their partners are
WOCBP.
6) 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) of subjects with Stage IV/recurrent NSCLC of
squamous histology who have been randomized to ipilimumab in addition to paclitaxel and carboplatin versus placebo in addition to paclitaxel and carboplatin. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall survival 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.5.2 | Secondary end point(s) |
- Overall Survival in All Randomized Subjects who Received at Least One Dose
of Blinded Study Therapy (OS2)
- Progression-Free Survival (PFS) per mWHO
- Best Overall Response Rate (BORR) per mWHO between the two treatment arms.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Time from date of randomization until the date of death
- Radiologic Assessments: CT/MRI imaging of the chest and abdomen is required at screening and every 6 weeks in the induction phase (from date of first blinded study drug dose) and every 12 weeks in the
maintenance phase until confirmed progressive disease (PD). Subjects who demonstrate PD at the week 7 tumor assessment will not be randomized into the study. Brain scan at screening is required to rule out the presence of brain metastases. |
|
| 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 | 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) | Yes |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 119 |
| 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 |
| Denmark |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Ireland |
| Israel |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Peru |
| Poland |
| Portugal |
| Romania |
| Russian Federation |
| Singapore |
| South Africa |
| Spain |
| Sweden |
| Switzerland |
| Taiwan |
| Thailand |
| Turkey |
| 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
|
Approximately 3 years (36 months) are estimated to be required to observe the necessary number of events for full information on the primary endpoint of overall survival. Subjects in the Follow-up phase will then be contacted by phone every 12 weeks to evaluate OS and collect data on the initiation of subsequent therapy for the treatment of lung cancer. Actual LPLV for the study is planned to occur in Jan 2016.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| 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 | 5 |
| 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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