Japanese Study of Ipilimumab Administered in Combination With Paclitaxel/Carboplatin in Patients With Nonsmall-cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01165216
First received: July 16, 2010
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

The primary purpose of this study was to establish the recommended dose of ipilimumab administered in combination with paclitaxel and carboplatin in Japanese patients with nonsmall-cell lung cancer.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Ipilimumab, 3 mg
Drug: Ipilimumab, 10 mg
Drug: Paclitaxel
Drug: Carboplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Ipilimumab (BMS-734016) in Combination With Paclitaxel and Carboplatin in Japanese Patients With Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants Experiencing a Dose-limiting Toxicity (DLT) [ Time Frame: Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4 ] [ Designated as safety issue: Yes ]
    A DLT was defined as study drug-related adverse event occurring during the first 2 cycles after ipilimumab administration in the induction phase and was any of the following: Grade 4 absolute neutrophil count (ANC) decreased (<500 cells/ mm^3) for 7 or more consecutive days; febrile Neutropenia (body temperature ≥38.5° C with ANC <1000 /mm^3) lasting >3 days; Grade 4 platelet count decreased (<25,000 cells/mm^3) or Grade 3 platelet count decreased requiring a platelet transfusion; Grade 3 or greater nausea, vomiting, diarrhea, despite the use of adequate/maximal medical intervention; Grade 3 or greater aspartate transaminase/alanine transaminase level and rash that has not resolved to Grade 2 or lower within 2 weeks after onset; or any Grade 3 or greater nonhematologic toxicity (except Grade 3 fatigue, Grade 3 asthenia, Grade 3 transient arthralgia/myalgia, or Grade 3 transient abnormal electrolyte levels).


Secondary Outcome Measures:
  • Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation [ Time Frame: Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug ] [ Designated as safety issue: Yes ]
    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. Treatment-related=having certain, probable, possible, or unknown relationship to study drug. AE incidence was assessed from Day 1 until Week 24 and every 12 weeks thereafter during the maintenance period, until discontinuation of study drug, due to progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure, and at least every 4 weeks(±1 week) until all study drug-related toxicities had recovered to resolved, stabilized or returned to baseline or were deemed irreversible during the follow-up period).

  • Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease [ Time Frame: Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6 ] [ Designated as safety issue: No ]
    Tumor response was determined for all participants with measurable lesions by radiologic responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The BOR was the best response recorded from start of treatment until disease progression/recurrence. RECIST for target lesions: PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. At minimum, tumor measurements were to be obtained at screening, every 6 weeks (±1 week) during the induction phase and every 12 weeks (±1 week) during the maintenance phase.

  • Maximum Serum Concentration (Cmax) of Ipilimumab [ Time Frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab ] [ Designated as safety issue: Yes ]
    Cmax was recorded directly from experimental observations. Actual times were used for the analyses. Cmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.

  • Trough Observed Serum Concentration (Cmin) of Ipilimumab [ Time Frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab ] [ Designated as safety issue: No ]
    Cmin was recorded directly from experimental observations. Actual times were used for the analyses. Cmin measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 (Day 8), and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure.

  • Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab [ Time Frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab ] [ Designated as safety issue: No ]
    The AUC(0-21d) was calculated using a mixture of log- and linear-trapezoidal summations. Using no weighting factor, the terminal log-liner phase of the concentration-time curve was determined by least-square linear regression of at least 3 data points. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods using a validated PK analysis program. Actual times were used for the analyses. AUC(0-21d) measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure.

  • Time of Maximum Observed Serum Concentration (Tmax) [ Time Frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab ] [ Designated as safety issue: No ]
    Tmax was recorded directly from experimental observations. Actual times were used for the analyses. Tmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.

  • Serum Half-life (T-HALF) of Ipilimumab [ Time Frame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab ] [ Designated as safety issue: No ]
    T-HALF was calculated as the ratio of ln(2) to elimination rate constant (K), where K was estimated as negative slope obtained by regression of the terminal log-linear portion of the serum concentration vs time profile following the ipilimumab dose on Day 1 of Cycle 3. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods, using a validated PK analysis program. Actual times were used for the analyses. T-HALF measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.


Enrollment: 15
Study Start Date: September 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
Drug: Ipilimumab, 3 mg
Intervenous (IV) injection, administered every 3 weeks for up to 6 cycles
Drug: Paclitaxel
IV injection, 175 mg/m^2, administered every 3 weeks for up to 6 cycles
Drug: Carboplatin
IV injection, AUC=6, administered every 3 weeks for up to 6 cycles. (AUC=area under the concentration curve)
Experimental: Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).
Drug: Ipilimumab, 10 mg
IV injection, administered every 3 weeks for up to 6 cycles
Other Name: BMS-734016
Drug: Paclitaxel
IV injection, 175 mg/m^2, administered every 3 weeks for up to 6 cycles
Drug: Carboplatin
IV injection, AUC=6, administered every 3 weeks for up to 6 cycles. (AUC=area under the concentration curve)

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Histologically or cytologically documented nonsmall-cell lung cancer (NSCLC) presenting as stage IIIB disease without indications for definitive radiotherapy, stage IV disease, or recurrent disease following radiation therapy or surgical resection
  • No prior chemotherapy, hormonal therapy, immunotherapy, or targeted-therapy—containing regimens for the treatment of NSCLC
  • Life expectancy of at least 3 months
  • Eastern Cooperative Oncology Group performance score of 0-1
  • Adequate bone marrow function
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count ≥1,500/mm^3
  • Platelet count ≥100,000/mm^3
  • Adequate liver function
  • Total bilirubin level ≤2.0*the upper limit of normal (ULN)
  • Asparate aminotransferase level ≤2.5*ULN
  • Alanine aminotransferase level ≤2.5*ULN
  • Adequate renal function
  • Calculated creatinine clearance based on Cockcroft and Gault formula ≥50 mL/min.

Key Exclusion Criteria:

  • Symptomatic central nervous system (CNS) metastasis or active CNS metastasis requiring medication
  • Malignant body cavity fluid (eg, pleural effusion, cardiac effusion, ascites) that recurred despite appropriate supportive care
  • Prior radiation of ≥30% of major bone-marrow containing areas (pelvis, lumbar spine)
  • Documented history of severe autoimmune or immune-mediated symptomatic disease that required prolonged (longer than 2 months) systemic immunosuppressant treatment
  • Documented history of motor neuropathy considered of autoimmune origin (eg, Guillain Barré syndrome)
  • Any concurrent malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, carcinoma of the mucous membrane of the gastrointestinal tract, or superficial bladder cancer treated with systemic therapy
  • ≥Grade 2 diarrhea
  • History of or concurrent disease of gastrointestinal tract perforations
  • ≥Grade 2 peripheral neuropathy (motor or sensory)
  • Uncontrolled intercurrent illness including infection requiring systemic therapy, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled angina pectoris, uncontrolled peptic ulcer, and cardiac arrhythmia requiring medication
  • Positive finding for human immunodeficiency virus antibody, hepatitis B surface antigen, or hepatitis C virus antibody.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165216

Locations
Japan
Local Institution
Chuo-ku, Tokyo, Japan, 1040045
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01165216     History of Changes
Other Study ID Numbers: CA184-113
Study First Received: July 16, 2010
Results First Received: June 23, 2014
Last Updated: June 23, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Carboplatin
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014