| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Study Population: Men and women who are ≥ 18 years old with histologically or cytologically confirmed lung cancer (Stage IIIb/IV NSCLC or extensive stage SCLC) with ECOG performance ≤ 1, who have met screening laboratory requirements, and who are previously untreated. Subjects with specific underlying autoimmune diseases (particularly gastrointestinal) or paraneoplastic syndromes related to SCLC will be excluded. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| 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 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| 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 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10041068 |
| E.1.2 | Term | Small cell lung cancer extensive stage |
|
| 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 the immune-related progression free survival (irPFS) of subjects receiving ipilimumab in combination with concurrent Taxol®/Paraplatin® (“concurrent”; Arm A) to that of subjects receiving Taxol®/Paraplatin® alone (Arm C) in Stage IIIb/IV NSCLC subjects using irRC as per the assessment of an independent review committee (IRC).
• To compare the immune-related progression free survival (irPFS) of subjects receiving ipilimumab in combination with sequential Taxol®/Paraplatin® (“sequential”; Arm B) to that of subjects receiving Taxol®/Paraplatin® alone (Arm C) in Stage IIIb/IV NSCLC subjects using irRC as per the assessment of an independent review committee (IRC). |
|
| E.2.2 | Secondary objectives of the trial |
To compare:
• PFS for the NSCLC subjects in Arm A vs. Arm C and Arm B vs Arm C using mWHO;
• The irPFS and PFS for extensive SCLC subjects in Arm A vs. Arm C and Arm B vs Arm C using the irRC and mWHO, respectively;
• Overall survival in Arm A vs Arm C and Arm B vs Arm C in subjects with NSCLC and in subjects with SCLC;
• Immune-related best overall response rate, immune-related disease control rate, best overall response rate, disease control rate of Arm A vs Arm C and Arm B vs Arm C;
To evaluate:
• The safety profile in each arm for subjects with NSCLC and for subjects with SCLC;
• The association between safety and efficacy in subjects with NSCLC and in subjects with SCLC;
• Candidate biomarkers of safety and/or efficacy in subjects with NSCLC and in subjects with SCLC;
• Health-related quality of life for subjects with NSCLC and for subjects with SCLC.
• Blood samples for pharmacokinetic evaluation of ipilimumab. |
|
| 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 |
Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific, version 2.0 dated 20-Jul-07
The objective of this Amendment is to permit the collection and storage of blood samples for use in future exploratory pharmacogenetic research studies. BMS will use DNA obtained from the blood sample and health information collected from the main clinical trial, CA184041 case report form, to study the association between genetic variation and drug response. BMS may also use the DNA to study the causes and further progression of lung cancer. Samples from this and other clinical studies may also be used in conjunction to accomplish this objective. |
|
| E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
a) Willing and able to give informed consent;
2) Target Population
a) Subjects with histologically- or cytologically-documented NSCLC (squamous,
adeno, large cell anaplastic, bronchioalveolar, and non-small cell carcinoma not
otherwise specified) who present with Stage IIIB/Stage IV disease (with managed
malignant pleural effusion), or recurrent disease following radiation therapy or
surgical resection. The cytological documentation of NSCLC may be from
brushing, washing or needle aspiration of a defined lesion but not from sputum
cytology alone.
OR
b) Subjects with histologically- or cytologically-documented SCLC who present
with extensive stage disease (e.g. tumor that is too widespread to be included
within the definition of limited-stage disease. Subjects with distant metastases
(M1) are always considered to have extensive-stage SCLC). The cytological
documentation of SCLC may be from brushing, washing or needle aspiration of a
defined lesion but not from sputum cytology alone.
c) Measurable tumor lesion as defined by modified WHO criteria (mWHO).
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 center(s).
3) Age and Sex
a) Men and women, ≥ 18 years of age
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
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 postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL). Even 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 (e.g., 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 prior to the start of investigational
product. |
|
| E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 8 weeks after the last dose of
ipilimumab.
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
d) Sexually active fertile men not using effective birth control if their partners are
WOCBP.
2) Target Disease Exceptions
a) History of or current brain metastases
3) Medical History and Concurrent Diseases
a) Autoimmune disease: subjects with a documented history of inflammatory bowel
disease, including ulcerative colitis and Crohn’s disease are excluded from this
study as are subjects with a history of symptomatic disease (e.g., rheumatoid
arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus
Erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis]);
b) History and/or concurrent paraneoplastic syndromes related to SCLC;
c) Dementia, altered mental status, or any psychiatric condition that would prohibit
the understanding or rendering of informed consent or completing questionnaires;
d) A serious uncontrolled medical disorder that, in the opinion of the Investigator,
would impair the ability of the subject to receive protocol therapy;
e) Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma
in situ of the cervix or prostate cancer;
f) Known HIV or Hepatitis B or Hepatitis C infection;
g) Subjects who received prior systemic therapy for lung cancer are excluded. Prior
radiation therapy or loco-regional surgeries are allowed if performed at least 3
weeks prior to randomization date;
h) Subjects with ≥ Grade 2 peripheral neuropathy (motor or sensory).
4) Physical and Laboratory Test Findings
a) Inadequate hematologic function defined by an absolute neutrophil count (ANC)
< 1,500/mm3, a platelet count < 100,000/mm3, or a hemoglobin level < 9 g/dL.
b) Inadequate hepatic function defined by a total bilirubin level ≥ 2.5 times the upper
limit of normal (ULN), AST and ALT levels ≥ 2.5 times the ULN or ≥ 5 times the
ULN if liver metastases are present.
c) Inadequate renal function defined by a serum creatinine level ≥ 2.5 times the
ULN.
d) Inadequate creatinine clearance defined as less than 50 mL/min.
5) Prohibited Treatments and/or Therapies
a) Chronic use of immunosuppressants and/or systemic corticosteroids (used in the
management of cancer or non-cancer-related illnesses). However, use of
corticosteroids are allowed if used as premedication for Taxol® infusion, treating
irAEs, or adrenal insufficiencies.
b) Any non-oncology vaccine therapy used for prevention of infectious diseases (for
up to 4 weeks prior to or after any dose of ipilimumab).
c) Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist.
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 (e.g. infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is progression free survival using irRC (as per the IRC assessment) in NSCLC.
Secondary endpoints include overall survival (OS) and response-related endpoints such as disease control rate (DCR), best overall response rate (BORR), duration of response using both the mWHO (as per IRC TA) and irRC as per both IRC and the investigator.
The pharmacokinetics (PK) of ipilimumab, pharmacodynamic markers of immunogenicity (HAHA), predictive biomarkers and HRQoL in NSCLC and SCLC subjects will also be evaluated. |
|
| 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 | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 28 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
