Clinical trial NCT00527735: Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC)
Official title: A Randomized, Double Blind, Parallel, Three Arm Trial Evaluating the Efficacy and Safety of Ipilimumab (BMS-734016) in Combination With Paclitaxel/Carboplatin Compared to Paclitaxel/Carboplatin Alone in Previously Untreated Subjects With Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung
Keywords: Non Small Cell Lung Cancer (NSCLC)
Small Cell Lung Cancer (SCLC)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-09-11
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine whether ipilimumab given with paclitaxel/carboplatin has clinical benefit when compared with paclitaxel/carboplatin alone in patients with previously untreated lung cancer.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed lung cancer (Stage IIIb/IV nonsmall-cell lung cancer or extensive stage small-cell lung cancer \[SCLC\])
* Measurable tumor lesion (as long as it is not located in a previously irradiated area) as defined by modified World Health Organization criteria
* Eastern Cooperative Oncology Group performance status of ≤1 at study entry
* Accessible for treatment and follow-up

Exclusion Criteria:

* Brain metastases
* Malignant pleural effusion
* Autoimmune disease
* Motor neuropathy of autoimmune origin
* SCLC-related paraneoplastic syndromes
* Any concurrent malignancy other than nonmelanoma skin cancer; carcinoma in situ of the cervix or breast; or prostate cancer treated with systemic therapy (participants with a previous malignancy but without evidence of disease for 5 years were allowed to enter the study)
* Prior systemic therapy for lung cancer. Prior radiation therapy or locoregional surgeries performed later than at least 3 weeks prior to randomization date were allowed.

  * Grade 2 peripheral neuropathy (motor or sensory)
* Known HIV or hepatitis B or C infection
* Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or noncancer-related illnesses). However, use of corticosteroids was allowed if used as premedication for paclitaxel infusion or for treating immune-related adverse events or adrenal insufficiencies.
* Inadequate hematologic function defined by an absolute neutrophil count \<1,500/mm\^3, a platelet count \<100,000/mm\^3, or hemoglobin level \<9 g/dL.
* Inadequate hepatic function defined by a total bilirubin level \>2.0 times the upper limit of normal (ULN), or ≥2.5 times the ULN if liver metastases are present, aspartate aminotransferase and alanine aminotransferase levels ≥2.5 times the ULN or ≥5 times the ULN if liver metastases are present.
* Inadequate renal function defined by a serum creatinine level ≥2.5 times the ULN
* Inadequate creatinine clearance defined as less than 50 mL/min.

Primary outcomes:
measure: Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)
timeFrame: Tumor assessed at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until immune-related Progressive Disease (irPD) or death (of censored, maximum reached: 16.5 months)
Secondary outcomes:
measure: Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria
timeFrame: Randomization date to date of progression or death (of censored, maximum reached: 13.6 months)
measure: Overall Survival in Participants With NSCLC
timeFrame: Randomization date to date of death (of censored, maximum reached: 26.5 months)
measure: Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC
timeFrame: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance
measure: Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)
timeFrame: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance
measure: Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC
timeFrame: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until irPD, progressive disease, or death (maximum reached: 22 months)
measure: Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC
timeFrame: Date of irCR or irPR to date of irPD or death (maximum reached: 14.2 months)
measure: Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade
timeFrame: Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)
measure: Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
timeFrame: At screening; predose Day 1; and Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent
measure: irPFS in Participants With SCLC Per irRC
timeFrame: Randomization date to date of irPD or death (maximum reached: 22 months)
measure: Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade
timeFrame: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent
measure: Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
timeFrame: At screening; Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent
measure: Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade
timeFrame: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
measure: Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline
timeFrame: Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
measure: Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade
timeFrame: Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)
measure: Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
timeFrame: At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment
measure: Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade
timeFrame: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
measure: Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade
timeFrame: At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment
measure: Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria
timeFrame: Randomization date to date of progression or death (of censored, maximum reached: 22 months)
measure: Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
timeFrame: Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment
measure: Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline
timeFrame: Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
measure: Overall Survival in Participants With SCLC
timeFrame: Randomization date to date of death (of censored, maximum reached: 22 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Hematology & Oncology Assoc. Llc
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: Acrc/Arizona Clinical Research Center, Inc.
state: Arizona
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group, Inc.
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Institute, Inc
state: California
city: Montebello
country: United States
facility: Oncology Care Medical Associates
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: San Diego
country: United States
facility: Sharp Clinical Oncology Research
state: California
city: Orlando
country: United States
facility: M D Anderson Cancer Center- Orlando
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Chicago
country: United States
facility: University Of Chicago Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Local Institution
state: Illinois
city: Hazard
country: United States
facility: Kentucky Cancer Clinic
state: Kentucky
city: Hagerstown
country: United States
facility: The John R. Marsh Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: The Cancer Center
state: Minnesota
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Local Institution
state: New York
city: Concord
country: United States
facility: Cmc-Northeast/ Northeast Oncology Associates
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Hematology Oncology Consultants, Inc
state: Ohio
city: Langhorne
country: United States
facility: St. Mary Medical Center
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinical Research
state: Pennsylvania
city: Sumter
country: United States
facility: Santee Hematology/Oncology
state: South Carolina
city: Lubbock
country: United States
facility: Southwest Cancer Treatment And Research Center
state: Texas
city: Belfort
country: France
facility: Local Institution
city: Caen
country: France
facility: Local Institution
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Rennes Cedex 9
country: France
facility: Local Institution
city: Bochum
country: Germany
facility: Local Institution
city: Coswig
country: Germany
facility: Local Institution
city: Ebensfeld
country: Germany
facility: Local Institution
city: Grosshansdorf
country: Germany
facility: Local Institution
city: Halle (Saale)
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Koeln
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Navrangpura, Ahmedabad
country: India
facility: Local Institution
state: Gujarat
city: Manipal
country: India
facility: Local Institution
state: Karnataka
city: Trivandrum
country: India
facility: Local Institution
state: Kerala
city: Vellore
country: India
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Siena
country: Italy
facility: Local Institution
city: Torino
country: Italy
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Olsztyn
country: Poland
facility: Local Institution
city: Szczecin
country: Poland
facility: Local Institution
city: Arkhangelsk
country: Russian Federation
facility: Local Institution
city: Chelyabinsk
country: Russian Federation
facility: Local Institution
city: Ivanovo
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Pyatigorsk
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: Sochi
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Dnipropetrovsk
country: Ukraine
facility: Local Institution
city: Donetsk
country: Ukraine
facility: Local Institution
city: Kharkov
country: Ukraine
facility: Local Institution
city: Lviv
country: Ukraine
facility: Local Institution
city: Ternopol
country: Ukraine
facility: Local Institution
city: Uzhgorod
country: Ukraine
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: