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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00918203
First received: June 9, 2009
Last updated: February 11, 2014
Last verified: March 2013
  Purpose

The purpose of this study is to determine if patients with untreated locally advanced or metastatic non-small cell lung cancer have a better outcome when treated with IMC-3G3 in combination with paclitaxel/carboplatin then when treated with paclitaxel/carboplatin alone.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Biological: IMC-3G3
Drug: Paclitaxel
Drug: carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study of Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) With Paclitaxel/Carboplatin or Paclitaxel/Carboplatin Alone in Previously Untreated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Approximately week 18 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety Profile in each arm, determined by number of Participants with Adverse Events [ Time Frame: Approximately week 18 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of IMC-3G3 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 [ Time Frame: Approximately week 18 ] [ Designated as safety issue: Yes ]
  • Radiographic objective response rate (ORR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Approximately week 18 ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Approximately week 18 ] [ Designated as safety issue: No ]
  • Median duration of response [ Time Frame: Approximately week 18 ] [ Designated as safety issue: No ]
  • Pharmacodynamic profile of IMC-3G3, determined by analysis of pharmacodynamic markers VEGF and PDGF [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: No ]
  • Immunogenicity of IMC-3G3, determined by Anti-IMC-3G3 antibody sampling [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics - Area under the curve (AUC) of IMC-3G3 for participants in Experimental Arm [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Maximum concentration (Cmax) of IMC-3G3 for participants in Experimental Arm [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Half-Life (t1/2) of IMC-3G3 for participants in Experimental Arm [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Clearance (Cl) of IMC-3G3 for participants in Experimental Arm [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Steady State Volume of Distribution (Vss) of IMC-3G3 for participants in Experimental Arm [ Time Frame: Approximately Week 12 ] [ Designated as safety issue: No ]

Enrollment: 137
Study Start Date: January 2010
Estimated Study Completion Date: June 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Paclitaxel + Carboplatin

(Initial 4-6 cycles) Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin 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

Patients who experience progressive disease may cross over to IMC-3G3 monotherapy.

Drug: Paclitaxel
200 mg/m2 is then administered I.V. over 3 hours
Drug: carboplatin
AUC=6 administered I.V. over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of paclitaxel/carboplatin are reached the patient may continue on IMC-3G3 maintenance for up to 12 months.
Experimental: IMC-3G3 + Paclitaxel + Carboplatin

(Initial 4-6 cycles)

IMC-3G3 15 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

Patients can remain on study after completing chemotherapy and receive IMC- 3G3 monotherapy on Days 1 and 8, provided there is ongoing evidence of clinical benefit.

Biological: IMC-3G3
15 mg/kg of IMC-3G3 on Days 1, 8, and 15 of each 21-day cycle, administered as an I.V. infusion at 25mg/min, with a minimum infusion time of 30 minutes.
Other Name: LY3012207
Drug: Paclitaxel
200 mg/m2 is then administered I.V. over 3 hours
Drug: carboplatin
AUC=6 administered I.V. over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of paclitaxel/carboplatin are reached the patient may continue on IMC-3G3 maintenance for up to 12 months.

Detailed Description:

The primary objective of this study is to evaluate the progression-free survival (PFS) in previously untreated patients with Stage IIIB/IV non-small cell lung cancer (NSCLC) treated with IMC-3G3 plus paclitaxel and carboplatin versus paclitaxel and carboplatin in the first-line metastatic setting.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient 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 patient 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 patient 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 patient's Eastern Cooperative Oncology Group (ECOG) performance status is 0-1
  5. The patient's age at the time of study entry is ≥ 18 years
  6. The patient 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 patient 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 patient 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 patient 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 patient 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. Patients 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 IMC-3G3 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
  12. The patient has resolution to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4 (NCI-CTCAE v 4.02) of all clinically significant toxic effects of prior locoregional therapy, surgery, chemoembolization, or other anticancer therapy. The exceptions for such effects are events that pertain to the lab values found elsewhere in these inclusion criteria. (For example, criterion # 6 states that a patient with hemoglobin ≥ 9.5 g/dL is considered eligible, even though NCI-CTCAE v 4.02 defines this value as Grade 2 anemia.)
  13. The patient has a life expectancy of ≥ 3 months
  14. The patient has provided signed informed consent

Exclusion Criteria:

  1. The patient has untreated central nervous system (CNS) metastases. Patients 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 patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or of intratumor cavitation
  3. The patient received prior systemic chemotherapy or biologic therapy (eg erlotinib) for Stage IIIB/IV NSCLC outside of the adjuvant setting. Patients who received prior cytotoxic chemotherapy or biologic therapy in the adjuvant setting will not be excluded based on such therapy
  4. The patient 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 patient 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 patient 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 patient has an uncontrolled thrombotic or hemorrhagic disorder
  8. The patient has a history of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of randomization
  9. The patient has a serious non-healing wound, ulcer, or bone fracture within 28 days prior to randomization
  10. The patient has undergone major surgery within 28 days prior to randomization
  11. The patient 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 patient has an elective or a planned major surgery to be performed during the course of the trial
  13. The patient has peripheral neuropathy ≥ Grade 2 NCI-CTCAE v 4.02
  14. The patient has known human immunodeficiency virus (HIV) positivity
  15. The patient, if female, is pregnant or lactating
  16. The patient has received previous therapy with any agent that targets PDGF or PDGFR
  17. The patient has a known allergy to any of the treatment components
  18. The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-3G3
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00918203

  Show 23 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00918203     History of Changes
Other Study ID Numbers: 13900, CP15-0804, I5B-IE-JGDB
Study First Received: June 9, 2009
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Eli Lilly and Company:
Lung neoplasms
IMC-3G3
carboplatin
paclitaxel
PDGFr

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

ClinicalTrials.gov processed this record on April 23, 2014