Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC)

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00527735
• Other study ID #: CA184-041
• Status: Completed
• Phase: Phase 2
• Start date: February 2008
• Est. completion date: December 2011

Study information

• Verified date: June 2018
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: December 2011
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Ipilimumab
Ipilimumab, 10 mg/kg, administered as a single-dose, intravenously (IV), over 90 minutes depending on randomization every 3 weeks (up to 6 doses). Participants could receive additional maintenance ipilimumab at a dose of 10 mg/kg every 12 weeks starting 24 weeks after the first ipilimumab dose.
• Placebo
Matched placebo for ipilimumab administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants could also receive additional maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first placebo dose.
• Paclitaxel
175 mg/m^2, administered as a single IV dose over 3 hours every 3 weeks (up to 6 doses). Dose modifications (reductions as well as delays) done as per product label.
• Carboplatin
Area under the concentration curve (AUC)=6, administered as a single IV dose over 30 minutes every 3 weeks (up to 6 doses) as per randomization. Dose modifications (reductions as well as delays) done as per product label.

Locations

Country	Name	City	State
France	Local Institution	Belfort
France	Local Institution	Caen
France	Local Institution	Marseille Cedex 9
France	Local Institution	Rennes Cedex 9
Germany	Local Institution	Bochum
Germany	Local Institution	Coswig
Germany	Local Institution	Ebensfeld
Germany	Local Institution	Grosshansdorf
Germany	Local Institution	Halle (Saale)
Germany	Local Institution	Hamburg
Germany	Local Institution	Koeln
Germany	Local Institution	Leipzig
Germany	Local Institution	Mainz
Germany	Local Institution	Muenchen
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Manipal	Karnataka
India	Local Institution	Navrangpura, Ahmedabad	Gujarat
India	Local Institution	Trivandrum	Kerala
India	Local Institution	Vellore
Italy	Local Institution	Genova
Italy	Local Institution	Siena
Italy	Local Institution	Torino
Poland	Local Institution	Gdansk
Poland	Local Institution	Krakow
Poland	Local Institution	Olsztyn
Poland	Local Institution	Szczecin
Russian Federation	Local Institution	Arkhangelsk
Russian Federation	Local Institution	Chelyabinsk
Russian Federation	Local Institution	Ivanovo
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Pyatigorsk
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Sochi
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Ukraine	Local Institution	Dnipropetrovsk
Ukraine	Local Institution	Donetsk
Ukraine	Local Institution	Kharkov
Ukraine	Local Institution	Lviv
Ukraine	Local Institution	Ternopol
Ukraine	Local Institution	Uzhgorod
United States	Georgia Cancer Specialists	Atlanta	Georgia
United States	Birmingham Hematology & Oncology Assoc. Llc	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gabrail Cancer Center	Canton	Ohio
United States	University Of Chicago Medical Center	Chicago	Illinois
United States	Hematology Oncology Consultants, Inc	Columbus	Ohio
United States	Cmc-Northeast/ Northeast Oncology Associates	Concord	North Carolina
United States	Compassionate Cancer Care Medical Group	Corona	California
United States	Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California
United States	The John R. Marsh Cancer Center	Hagerstown	Maryland
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	St. Mary Medical Center	Langhorne	Pennsylvania
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	The Angeles Clinic & Research Institute, Inc	Los Angeles	California
United States	Southwest Cancer Treatment And Research Center	Lubbock	Texas
United States	The Cancer Center	Minneapolis	Minnesota
United States	Oncology Care Medical Associates	Montebello	California
United States	Local Institution	New York	New York
United States	M D Anderson Cancer Center- Orlando	Orlando	Florida
United States	Local Institution	Park Ridge	Illinois
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	Sharp Clinical Oncology Research	San Diego	California
United States	Guthrie Clinical Research	Sayre	Pennsylvania
United States	Mayo Clinic	Scottsdale	Arizona
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	Acrc/Arizona Clinical Research Center, Inc.	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Germany,  India,  Italy,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)	irPFS is defined as the time between the randomization date and date of immune-related Progressive Disease (irPD) (at least 25% increase percentage change in total tumor burden, including new lesions) or death, whichever occurs first. For patients with no recorded postbaseline tumor assessments, irPFS is censored at randomization. Participant who die without reported irPD are considered to have progressed on the date of death. For those who remain alive and have no irPD, irPFS is censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.	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	Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria	By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.	Randomization date to date of progression or death (of censored, maximum reached: 13.6 months)
Secondary	Overall Survival in Participants With NSCLC	Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.	Randomization date to date of death (of censored, maximum reached: 26.5 months)
Secondary	Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC	mWHO criteria define BORR as the number of patients with best overall response of Complete Response (CR) or Partial Response (PR), divided by the total number of participants in the data set (multiplied by 100 for percentage). CR=Complete disappearance of all index lesions; PR=decrease from baseline of >=50% in the sum of products of the 2 largest perpendicular diameters of all index lesions. Independent review committee performed tumor assessment.	Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance
Secondary	Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)	irBORR=number of participants with irBORR of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), divided by total participants in the data set. irCR=Complete disappearance of all index lesions. irPR=Decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index and of all new measurable lesions. Independent review committee performed the tumor assessments.	Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance
Secondary	Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC	irDCR is defined as the proportion of participants whose immune-related best overall response is irPR, irCR, or immune-related Stable Disease (irSD) in the analysis data set. irSD=Does not meet criteria for irCR or irPR, in the absence of progressive disease. By mWHO criteria, DCR is defined as the proportion of participants whose best overall response is PR, CR, or SD in the analysis data set. SD=A decrease or tumor stabilization of 1 or more nonindex lesions. Independent review committee assessed response.	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)
Secondary	Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC	irDoR is defined as the time between the date of response of confirmed irCR or irPR and the date of irPD or death, whichever occurs first. For those participants who remain alive and did progress following response, irDoR was censored on the date of last evaluable tumor assessment. By mWHO criteria, DoR is defined as the time between the date of response of confirmed CR or PR and the date of PD or death, whichever occurs first. For those who remain alive and did not progress following response, DoR was censored on the date of last evaluable tumor assessment.	Date of irCR or irPR to date of irPD or death (maximum reached: 14.2 months)
Secondary	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	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.	Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)
Secondary	Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade	CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:	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
Secondary	irPFS in Participants With SCLC Per irRC	IRC performed TA.	Randomization date to date of irPD or death (maximum reached: 22 months)
Secondary	Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade	ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.	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
Secondary	Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings	Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.	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
Secondary	Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade	ULN=upper limit of normal. Lipase (U/L) Gr 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Grade 2 >1.5 to 2.0*ULN, Grade 3 >2.0 to 5.0*ULN, Grade 4 >5.0*ULN. Creatine (mg/dL) Grade 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.	At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
Secondary	Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline	An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.	Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
Secondary	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	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.	Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)
Secondary	Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade	CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Gr 1:	At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment
Secondary	Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade	ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. ULN=Upper limit of normal among all laboratory ranges. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.	At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
Secondary	Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade	ULN=upper limit of normal. Lipase (U/L) Grade (Gr) 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Gr 2 >1.5 to 2.0*ULN, Gr 3 >2.0 to 5.0*ULN, Gr 4 >5.0*ULN. Creatine (mg/dL) Gr 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.	At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment
Secondary	Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria	By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment.	Randomization date to date of progression or death (of censored, maximum reached: 22 months)
Secondary	Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings	Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.	Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment
Secondary	Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline	An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.	Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment
Secondary	Overall Survival in Participants With SCLC	Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.	Randomization date to date of death (of censored, maximum reached: 22 months)

External Links

•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm