A Study of Necitumumab in the First-Line Treatment of Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT01763788

Last Updated: 2019-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-07
• Study Completion Date: 2018-10-17

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.

Conditions

Squamous Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Necitumumab + Gem and Cis

Phase 1b Dose Escalation: Necitumumab 800 milligram (mg) on Days 1 and 8 of every 21 day cycle, administered as an intravenous (IV) infusion. Gemcitabine (Gem) dose escalation of 1000 or 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles. Cisplatin (Cis) 75 mg/m^2 on Day 1 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles.

Phase 2 Randomized: Necitumumab 800 mg on Days 1 and 8 of every 21 day cycle, administered as an IV infusion. Gemcitabine at fixed dose determined in Phase 1b (1000 or 1250 mg/m^2) on Days 1 and 8 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles. Cisplatin 75 mg/m^2 on Day 1 of every 21 day cycle, administered as an IV infusion for a maximum of 4 cycles.

Group Type: EXPERIMENTAL

Necitumumab

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Cisplatin

Intervention Type: DRUG

Administered IV

Gemcitabine + Cisplatin

Phase 2 Randomized: Gemcitabine at fixed dose determined in Phase 1b (1000 to 1250 mg/m\^2) on Day 1 and Day 8 of every 21 day cycle,administered as an IV infusion over approximately 30 minutes for a maximum of 4 cycles. Cisplatin 75 mg/m\^2 on Day 1 of every 21 day cycle, administered as an IV infusion over approximately 120 minutes for a maximum of 4 cycles .

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Administered IV

Cisplatin

Intervention Type: DRUG

Administered IV

Interventions

Necitumumab

Administered IV

Intervention Type: DRUG

Gemcitabine

Administered IV

Intervention Type: DRUG

Cisplatin

Administered IV

Intervention Type: DRUG

Other Intervention Names

IMC-11F8; LY3012211; LY188011

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

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.

Aichi, , Japan

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.

Chiba, , Japan

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.

Ehime, , Japan

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.

Fukuoka, , Japan

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.

Hokkaido, , Japan

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.

Hyōgo, , Japan

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.

Ishikawa, , Japan

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.

Kanagawa, , Japan

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.

Kōtoku, , Japan

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.

Miyagi, , Japan

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.

Nagasaki, , Japan

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.

Niigata, , Japan

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.

Okayama, , Japan

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.

Osaka, , Japan

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.

Ōita, , Japan

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.

Saitama, , Japan

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.

Sendai, , Japan

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.

Shizuoka, , Japan

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.

Wakayama, , Japan

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.

Yamaguchi, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 30797492 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

I4X-JE-JFCM

Identifier Type: OTHER

Identifier Source: secondary_id

14461

Identifier Type: -

Identifier Source: org_study_id