A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

NCT00918203 | Completed Phase 2 Results DMC

• 3 other identifiers: 13900CP15-0804I5B-IE-JGDB
• Study Type: interventional
• Target: 137
• Locations: 2 countries
• Sites: 23

Brief Summary

The purpose of this study is to determine if participants with untreated locally advanced or metastatic non-small cell lung cancer have a better outcome when treated with olaratumab in combination with paclitaxel/carboplatin then when treated with paclitaxel/carboplatin alone.

Conditions

Non-Small Cell Lung Cancer

Keywords

Lung neoplasms; IMC-3G3; carboplatin; paclitaxel; PDGFr

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from the day of randomization to the first evidence of progression by RECIST version 1.1, or death from any cause. Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of their last tumor assessment. If there was no radiologic assessment at baseline or post baseline, participants were censored at the date of randomization. If death or progressive disease (PD) occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.

  Baseline to Measured PD or Death From Any Cause (Up to 31 Months)

Secondary Outcomes (12)

• Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  Baseline to Study Completion (Up to 43 Months)

• Safety and Tolerability of Olaratumab Administered at a More Rapid Rate (25mg/Min With Minimum Infusion Time of 30 Minutes), Determined by Number of Participants With Treatment Related Adverse Events

  Up to 43 Months

• Overall Survival (OS)

  Baseline to Death From Any Cause (Up to 31 Months)

• Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)

  Baseline to Measured PD or Study Discontinuation (Up to 31 Months)

• Median Duration of Response

  First Criteria Met for CR or PR to Measured PD Start of Other Antitumor Therapy or Death From Any Cause (Up to 31 Months)

Study Arms (2)

Paclitaxel + Carboplatin

ACTIVE COMPARATOR

(Initial 4-6 cycles) Paclitaxel 200 milligram/square meter (mg/m2) over 3 hrs (Day 1) Carboplatin Area Under Concentration (AUC)=6 (Day 1) of each 21-day cycle (Initial 4-6 cycles) Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Participants who experience progressive disease may cross over to olaratumab monotherapy.

Drug: Paclitaxel; Drug: Carboplatin

Olaratumab + Paclitaxel + Carboplatin

EXPERIMENTAL

(Initial 4-6 cycles) Olaratumab 15 milligrams/kilogram (mg/kg) over 30 mins (Days 1 and 8) plus Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Participants can remain on study after completing chemotherapy and receive olaratumab monotherapy on Days 1 and 8, provided there is ongoing evidence of clinical benefit.

Biological: Olaratumab; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Olaratumab BIOLOGICAL

15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, administered intravenously (IV) at 25 milligram/minute (mg/min), with a minimum infusion time of 30 minutes.

Also known as: LY3012207, IMC-3G3

Olaratumab + Paclitaxel + Carboplatin

Paclitaxel DRUG

200 mg/m2 is then administered IV over 3 hours

Olaratumab + Paclitaxel + Carboplatin; Paclitaxel + Carboplatin

Carboplatin DRUG

AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.

Olaratumab + Paclitaxel + Carboplatin; Paclitaxel + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participants has histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC)Stage IIIB with effusion. Mixed Non-Small Cell Lung Cancer (NSCLC) tumors will be categorized by the predominant cell type. Primary or metastatic site may be used for histology
• For squamous cell histology or for centrally located mediastinal masses (\< 3 cm from the carina) identified by computed tomography scan (CT) or chest x-ray, the participant must undergo a magnetic resonance imaging (MRI) of the chest or I.V. contrast CT scan within 3 weeks of randomization, to exclude major airway or blood vessel invasion (in the investigator's opinion) by cancer
• The participant has measurable disease (Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-1
• The participant's age at the time of study entry is ≥ 18 years
• The participant has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9.5 g/dL, and a platelet count ≥ 100,000/μL obtained within 2 weeks prior to randomization
• The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × the upper limit of normal (ULN), or ≤ 5 × the ULN in the presence of known liver metastases)
• The participant has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the patient's creatinine clearance (CrCl) is ≥ 60 mL/min
• The participant has urinary protein ≤ 1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate \< 1 g of protein in 24 hours to allow participation
• The participant has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN if not receiving anticoagulation therapy. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, have therapeutic INR, no active bleeding (defined as within 14 days randomization) and no pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices)
• Because the teratogenicity of Olaratumab is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization and for the duration of study participation
• The participant has a life expectancy of ≥ 3 months
• The participant has provided signed informed consent

You may not qualify if:

• The participant has untreated central nervous system (CNS) metastases. Participants are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radiosurgery)ending at least 2 weeks prior to randomization, or after surgical resection performed at least 4 weeks prior to randomization
• The participant has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or of intratumor cavitation
• The participant received prior systemic chemotherapy or biologic therapy (eg erlotinib) for Stage IIIB/IV NSCLC outside of the adjuvant setting. Participants who received prior cytotoxic chemotherapy or biologic therapy in the adjuvant setting will not be excluded based on such therapy
• The participant has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer b) curatively treated cervical carcinoma in situ c)other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to randomization
• The participant is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent
• The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• The participant has an uncontrolled thrombotic or hemorrhagic disorder
• The participant has a history of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of randomization
• The participant has a serious non-healing wound, ulcer, or bone fracture within 28 days prior to randomization
• The participant has undergone major surgery within 28 days prior to randomization
• The participant has received adjuvant chemotherapy 21 days prior to randomization or has participated in clinical trials of experimental agents within 28 days prior to randomization
• The participant has an elective or a planned major surgery to be performed during the course of the trial
• The participant has peripheral neuropathy ≥ Grade 2 NCI-CTCAE v 4.02
• The participant has known human immunodeficiency virus (HIV) positivity
• The participant, if female, is pregnant or lactating

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (23)

ImClone Investigational Site

Birmingham, Alabama, 35294, United States

Location

ImClone Investigational Site

Bakersfield, California, 93309, United States

Location

ImClone Investigational Site

Highland, California, 92346, United States

Location

ImClone Investigational Site

Stamford, Connecticut, 06902, United States

Location

ImClone Investigational Site

Port Saint Lucie, Florida, 34952, United States

Location

ImClone Investigational Site

Joliet, Illinois, 60435, United States

Location

ImClone Investigational Site

Baton Rouge, Louisiana, 70809, United States

Location

ImClone Investigational Site

St Louis, Missouri, 63110, United States

Location

ImClone Investigational Site

Charlotte, North Carolina, 28203, United States

Location

ImClone Investigational Site

Gastonia, North Carolina, 20854, United States

Location

ImClone Investigational Site

Huntersville, North Carolina, 28078, United States

Location

ImClone Investigational Site

Canton, Ohio, 44708, United States

Location

ImClone Investigational Site

Cleveland, Ohio, 44106, United States

Location

ImClone Investigational Site

Cleveland, Ohio, 44195, United States

Location

ImClone Investigational Site

Massillon, Ohio, 44646, United States

Location

ImClone Investigational Site

Portland, Oregon, 97239, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

ImClone Investigational Site

Dallas, Texas, 75390-8852, United States

Location

ImClone Investigational Site

Round Rock, Texas, 78665, United States

Location

ImClone Investigational Site

Temple, Texas, 76508, United States

Location

ImClone Investigational Site

Madison, Wisconsin, 53792, United States

Location

ImClone Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

ImClone Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

olaratumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2009
• First Posted: June 11, 2009
• Study Start: January 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: November 17, 2017
• Last Updated: January 10, 2019
• Results First Posted: January 16, 2017

Record last verified: 2018-12

Locations

CA (2); US (21)