Clinical trial NCT01763788: A Study of Necitumumab in the First-Line Treatment of Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)
Official title: An Open-Label, Multicenter, Phase 1b/2 Study to Evaluate Necitumumab in Combination With Gemcitabine and Cisplatin in the First-Line Treatment of Patients With Advanced (Stage IV) Squamous Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Squamous Non-small Cell Lung Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-01-09
Enrollment: 192
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the Phase 1b portion of the study is to investigate how the body tolerates necitumumab, in combination with gemcitabine and cisplatin chemotherapy as first line treatment in participants with Stage IV squamous NSCLC and to determine the recommended dose for the subsequent Phase 2 portion of the study.

The purpose of the Phase 2 portion of the study is to evaluate the efficacy of necitumumab in combination with gemcitabine and cisplatin chemotherapy in participants with Stage IV squamous NSCLC in a first-line setting.


Eligibility criteria: Inclusion Criteria:

* Squamous Non-Small Cell Lung Cancer Disease (NSCLC)
* Clinical Stage IV NSCLC
* Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
* No prior systematic chemotherapy, targeted therapy, surgery and chest radiotherapy
* Ha resolution to Grade less than or equal to (≤) 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0, of all clinically significant toxic effects of prior therapy for other than NSCLC
* Adequate-organ function defined as:
* Total bilirubin ≤1.5 x the upper limit of normal value (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
* Serum creatinine ≤ 1.2 x ULN or calculated creatinine clearance (CrCL)\>50 milliliter per minute (mL/min) (per the Cockcroft Gault formula or equivalent and/or 24-hour urine collection)
* Absolute neutrophil count (ANC) greater than or equal to ≥1.5 x 10\^3/μL(microliter)
* Hemoglobin ≥10.0 g/dL(gram per deciliter)
* Platelets ≥100 x 10\^3/μL
* At least 20 years of age
* Estimated life expectancy of at least 12 weeks
* A formalin-fixed, paraffin-embedded tumor tissue block or a minimum of 5 unstained slides of tumor sample prior to randomization for the evaluation of epidermal growth factor receptor (EGFR) protein expression (IHC).
* If women: surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate \<1%) during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method). If men: surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period.
* Has provided signed informed consent

Exclusion Criteria:

* Has enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device
* Participant has undergone major surgery within 28 days prior to enrollment or have planned major surgery, subcutaneous venous access device placement within 7 days prior to enrollment Phase 1b) or randomization (Phase 2).
* Has undergone any prior radiation therapy, except for Gamma Knife radiation and palliative radiation treatment at least 14 days have elapsed from last radiation treatment prior to enrollment (Phase 1b) or randomization (Phase 2)
* Has brain metastases that are symptomatic or require surgery, medication and radiotherapy except for stereotactic irradiation
* Has superior vena cava syndrome
* Has clinically relevant coronary artery disease or uncontrolled congestive - heart failure
* Participant has uncontrolled hypertension defined as systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg despite standard medical management.
* Has diabetes requiring insulin
* Has an angina or has experienced myocardial infarction within 6 months prior to enrollment (Phase 1b) or randomization (Phase 2)
* Has an Acquired Immunodeficiency Syndrome (AIDS)-related illness or have evidence of or test positive test results for human immunodeficiency virus (HIV)
* Has evidence of or test positive test results for hepatitis B, or hepatitis C virus antibodies
* Has a known allergy and history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab, or any other contraindication to one of the administered treatments
* Has significant third-space fluid retention requiring drainage
* Has history of interstitial pneumonitis
* Has an ongoing or active infection
* Has a history of significant neurological or psychiatric disorders
* Has a Grade 2 peripheral neuropathy
* Pregnant (confirmed within 7 days prior to enrollment \[Phase 1b\] or randomization \[Phase 2\]), or breastfeeding
* Has known history of drug abuse
* Assessed as inadequate for the study by the investigator or sub investigator

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 to Day 21 in Cycle 1 (Up To 21 days)
measure: Phase 2: Overall Survival (OS)
timeFrame: From Date of Randomization until Death Due to Any Cause (Up To 39 Months)
Secondary outcomes:
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up To 39 Months)
measure: Phase 1b: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])
timeFrame: Baseline to Measured Progressive Disease (Up To 39 Months)
measure: Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])
timeFrame: Baseline to Measured Progressive Disease (Up To 39 Months)
measure: Phase 2: Time to Treatment Failure (TTF)
timeFrame: From Date of Randomization to Measured Progressive Disease, Death Due to Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up To 39 Months)
measure: Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Index Score
timeFrame: Baseline, Cycle 4 (Cycle = 3 weeks)
measure: Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Visual Analog Scale (VAS)
timeFrame: Baseline, Cycle 4 (Cycle = 3 weeks)
measure: Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS)
timeFrame: Baseline, Cycle 4 (Cycle = 3 weeks)
measure: Phase 1b: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab
timeFrame: Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion
measure: Phase 1b: PK: Cmax of Gemcitabine and Cisplatin
timeFrame: Gemcitabine: Cycle 1(C1) Day1(D1): Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1 D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion
measure: Phase 1b: PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Necitumumab
timeFrame: Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion
measure: Phase 1b: PK: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Gemcitabine and Cisplatin
timeFrame: Gemcitabine: C1D1: Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion
measure: Phase 2: PK: Minimum Concentration (Ctrough) of Necitumumab
timeFrame: Predose Day 1 of Cycle 1, 2, 3, 4, and every 2 cycles after Cycle 5
measure: Phase 2: Number of Participants With Serum Anti-Necitumumab Antibody Assessment (Immunogenicity)
timeFrame: Baseline up to 30 Days Post Last Infusion (estimated up to 39 months)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Chiba
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Ehime
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Fukuoka
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Hokkaido
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Hyogo
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Ishikawa
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Kanagawa
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Koto-ku
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Miyagi
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Nagasaki
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Niigata
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Oita
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Okayama
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Osaka
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Saitama
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Sendai
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Shizuoka
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Wakayama
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Yamaguchi
country: Japan
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Watanabe S, Yoshioka H, Sakai H, Hotta K, Takenoyama M, Yamada K, Sugawara S, Takiguchi Y, Hosomi Y, Tomii K, Niho S, Yamamoto N, Nishio M, Ohe Y, Kato T, Takahashi T, Kamada A, Suzukawa K, Omori Y, Enatsu S, Nakagawa K, Tamura T. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan. Lung Cancer. 2019 Mar;129:55-62. doi: 10.1016/j.lungcan.2019.01.005. Epub 2019 Jan 16.