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

NCT ID: NCT00918203

Last Updated: 2019-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2017-11-17

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.

Detailed Description

The primary objective of this study is to evaluate the progression-free survival (PFS) in previously untreated participants with Stage IIIB/IV non-small cell lung cancer (NSCLC) treated with olaratumab plus paclitaxel and carboplatin versus paclitaxel and carboplatin in the first-line metastatic setting.

Conditions

Non-Small Cell Lung Cancer

Study Design

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

Study Groups

Paclitaxel + Carboplatin

(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.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

200 mg/m2 is then administered IV over 3 hours

Carboplatin

Intervention Type: 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

(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.

Group Type: EXPERIMENTAL

Olaratumab

Intervention Type: 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.

Paclitaxel

Intervention Type: DRUG

200 mg/m2 is then administered IV over 3 hours

Carboplatin

Intervention Type: 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.

Interventions

Olaratumab

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.

Intervention Type: BIOLOGICAL

Paclitaxel

200 mg/m2 is then administered IV over 3 hours

Intervention Type: DRUG

Carboplatin

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.

Intervention Type: DRUG

Other Intervention Names

LY3012207; IMC-3G3

Eligibility Criteria

Inclusion Criteria

1. 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

2. 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

3. 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

4. The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-1

5. The participant's age at the time of study entry is ≥ 18 years

6. 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

7. 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)

8. 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

9. 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

10. 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)

11. 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

13. The participant has a life expectancy of ≥ 3 months

14. The participant has provided signed informed consent

Exclusion Criteria

1. 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

2. The participant has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or of intratumor cavitation

3. 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

4. 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

5. 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

6. 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

7. The participant has an uncontrolled thrombotic or hemorrhagic disorder

8. The participant has a history of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of randomization

9. The participant has a serious non-healing wound, ulcer, or bone fracture within 28 days prior to randomization

10. The participant has undergone major surgery within 28 days prior to randomization

11. 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

12. The participant has an elective or a planned major surgery to be performed during the course of the trial

13. The participant has peripheral neuropathy ≥ Grade 2 NCI-CTCAE v 4.02

14. The participant has known human immunodeficiency virus (HIV) positivity

15. The participant, if female, is pregnant or lactating

16. The participant has received previous therapy with any agent that targets platelet derived growth factor (PDGF) or platelet derived growth factor receptor (PDGFR)

17. The participant has a known allergy to any of the treatment components

18. The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of Olaratumab

• Minimum Eligible Age: 18 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

ImClone Investigational Site

Birmingham, Alabama, United States

ImClone Investigational Site

Bakersfield, California, United States

ImClone Investigational Site

Highland, California, United States

ImClone Investigational Site

Stamford, Connecticut, United States

ImClone Investigational Site

Port Saint Lucie, Florida, United States

ImClone Investigational Site

Joliet, Illinois, United States

ImClone Investigational Site

Baton Rouge, Louisiana, United States

ImClone Investigational Site

St Louis, Missouri, United States

ImClone Investigational Site

Charlotte, North Carolina, United States

ImClone Investigational Site

Gastonia, North Carolina, United States

ImClone Investigational Site

Huntersville, North Carolina, United States

ImClone Investigational Site

Canton, Ohio, United States

ImClone Investigational Site

Cleveland, Ohio, United States

ImClone Investigational Site

Cleveland, Ohio, United States

ImClone Investigational Site

Massillon, Ohio, United States

ImClone Investigational Site

Portland, Oregon, United States

ImClone Investigational Site

Philadelphia, Pennsylvania, United States

ImClone Investigational Site

Dallas, Texas, United States

ImClone Investigational Site

Round Rock, Texas, United States

ImClone Investigational Site

Temple, Texas, United States

ImClone Investigational Site

Madison, Wisconsin, United States

ImClone Investigational Site

Calgary, Alberta, Canada

ImClone Investigational Site

Edmonton, Alberta, Canada

Countries

United States; Canada

Other Identifiers

CP15-0804

Identifier Type: OTHER

Identifier Source: secondary_id

I5B-IE-JGDB

Identifier Type: OTHER

Identifier Source: secondary_id

13900

Identifier Type: -

Identifier Source: org_study_id