Scientific Study to compare the efficiency of Ipilimumab combined with Paclitaxel and Carboplatin with Paclitaxel and carboplatin alone in the treatment of Stage IV/Recurrent Non-Small Cell Lung Cancer (NSCLC).
- Conditions
- MedDRA version: 18.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.0Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]Stage IV/Recurrent Non-Small Cell Lung Cancer
- Registration Number
- EUCTR2009-017396-19-CZ
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 920
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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 552
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 368
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: 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;Primary end point(s): Overall Survival (OS) of subjects with Stage IV/recurrent NSCLC of<br>squamous histology who have been randomized to ipilimumab in addition to paclitaxel and carboplatin versus placebo in addition to paclitaxel and carboplatin.;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<br>have not died, OS will be censored on the last date the subject was known to be alive.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Overall Survival in All Randomized Subjects who Received at Least One Dose<br>of Blinded Study Therapy (OS2)<br>- Progression-Free Survival (PFS) per mWHO <br>- Best Overall Response Rate (BORR) per mWHO between the two treatment arms.<br>;Timepoint(s) of evaluation of this end point: - Time from date of randomization until the date of death<br>- 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<br>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.