Preoperative Pemetrexed and Carboplatin for Select Stage IB, II, and III Non-Squamous Non-Small-Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00906282
• Recruitment Status: Completed
• First Posted: May 21, 2009
• Results First Posted: February 24, 2017
• Last Update Posted: February 24, 2017
• Sponsor: SCRI Development Innovations, LLC
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): SCRI Development Innovations, LLC

Study Description

Brief Summary:

The purpose of this multi-center Phase II trial is to examine the impact of pemetrexed/carboplatin in the preoperative treatment of patients with select stage IB, II,and III non-squamous NSCLC. Because patients with non-squamous type NSCLC have been shown to have better survival rates than patients with squamous tumors when given pemetrexed with a platinum agent, only patients with non-squamous NSCLC (adenocarcinoma, large cell, and undifferentiated), not including squamous histology, will be allowed to participate in this study. If this novel regimen proves to be safe and active in this setting, it will provide rationale for further investigation in a larger, prospective, randomized trial.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Pemetrexed; Drug: Carboplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Preoperative Pemetrexed and Carboplatin in Patients With Select Stage IB, II, and III Non-Squamous Non-Small-Cell Lung Cancer
• Study Start Date: June 2009
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pemetrexed/Carboplatin; 4 cycles of preoperative treatment (1 Cycle = 21 days): Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle; Carboplatin: AUC 6.0 by IV on Day 1 each cycle.	Drug: Pemetrexed; 500 mg/m2 IV over 10 minutes on Day 1 of every 3-week treatment cycle for a total of 4 cycles (12 weeks).; Other Name: Alimta; Drug: Carboplatin; AUC 6.0 IV on Day 1 of every 3-week treatment cycle for a total of 4 cycles (12 weeks).; Other Name: 41575-94-4

Outcome Measures

Primary Outcome Measures :

1. 3-Year Overall Survival Rate [ Time Frame: 36 months ]
   The percentage of patients who were alive at 3 years from time of first study treatment until date of death from any cause. Overall survival is shown for the Intent-to-Treat population.

Secondary Outcome Measures :

1. Objective Tumor Response [ Time Frame: At 6 and 12 weeks ]
   Objective Tumor Response defined as the percent of patients who completed up to 4 cycles of pre-operative chemotherapy and achieved a complete response (CR) or partial response (PR) assessed by Response Evaluation in Solid Tumors (RECIST) 1.0. Patients with stable disease (SD) or response to treatment were deemed surgical candidates. [CR=disappearance of all target tumors; PR= ≥30% decrease in the sum of the longest diameters of target tumors. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.]
2. Pathologic Response Rate [ Time Frame: weeks 15 -18 ]
   Percent of patients having a pathological complete or partial response (pCR or pPR) at surgery. pCR defined as complete removal of all tumor. pPR defined as residual viable tumor demonstrated in the resected specimen.
3. Rate of Residual Disease as an Assessment of Pathological Partial Response (pPR) [ Time Frame: At 15-18 weeks ]
   pPR was further assessed by the amount of residual tumor measured at surgery: microscopic residual disease = less than 1 centimeter (<1 cm); macroscopic residual disease = 1 centimeter or greater (≥1 cm).
4. Complete Resection Rate [ Time Frame: At weeks 15-18 ]
   The percent of patients who had surgical resection listed by procedure type: lobectomy or pneumonectomy, or resection of adjacent chest wall or mediastinal structures when appropriate. Surgery followed standard guidelines for resection of non-small-cell lung cancer (NSCLC).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically-confirmed NSCLC (adenocarcinoma, large cell, and undifferentiated). Patients with squamous histology are not eligible.
2. Life expectancy of at least 12 weeks.

3. Patients with the following stages of NSCLC:

   • T2 N0 tumors: Limited to tumors >=4 cm.
   • T1-2 N1 tumors.
   • T3 N0-1 tumors (excluding superior sulcus tumors): Including tumors involving the chest wall, proximal airway, or mediastinal pleura where preoperative radiotherapy is not planned.
   • T1-2 N2 tumors: For patients with N2 disease involving one zone (Upper zone (R), AP zone (L), subcarinal zone, or lower zone) and nodes <=2cm in diameter.
   • T4 N0-1 tumors (excluding superior sulcus tumors): T4 lesions other than malignant effusions where radiotherapy is not planned.
4. Patients with clinical N2 involvement must have histologic confirmation by mediastinoscopy (or alternate biopsy procedure).
5. Tumors should be considered potentially resectable.
6. No evidence of extrathoracic metastatic disease.
7. Patients must have measurable disease by RECIST criteria.
8. Patients must be candidates (medically) for chemotherapy followed by surgical resection.
9. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery; at least 3 weeks must have elapsed from the time of a major surgery.

10. Laboratory values as follows:

    • Absolute neutrophil count (ANC) >=1500/μL
    • Hemoglobin (Hgb) >=10 g/dL
    • Platelets >=100,000/uL
    • AST/SGOT and ALT/SGPT within normal limits (WNL)
    • Total bilirubin within normal limits (WNL)
    • Calculated creatinine clearance >=45 mL/min
11. ECOG Performance Status grade 0 or 1.
12. The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Alimta.
13. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
14. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
15. Patient must be accessible for treatment and follow-up.
16. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Patients with the following stages are excluded:

   • T1 N0;
   • T2 N0, with primary tumor <4 cm;
   • T1-2 N2, with multiple zones of N2 involvement;
   • T3-4 N2;
   • Any N3;
   • Any TxNxM1 disease; or
   • Any stage where surgery and/or chemoradiotherapy is the preferred initial approach in management, as deemed by the treating physician.
2. Squamous or predominant squamous mixed histologies.
3. Mixed small-cell and non-small cell histologies.
4. Pulmonary carcinoid tumors.
5. Presence of third space fluid which cannot be controlled by drainage.
6. Use of erythropoietin as a hematopoietic growth factor is not allowed.
7. Cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
8. Women who are pregnant (positive pregnancy test) or lactating.
9. Use of any non-approved or investigational agent within 30 days of administration of the first dose of study drug.
10. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
11. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
12. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
13. History of hypersensitivity to active or inactive excipients of any component of treatment.
14. Inability to comply with study and/or follow-up procedures.

Contacts and Locations

Locations

United States, Florida

Florida Cancer Specialists

Fort Myers, Florida, United States, 33901

United States, Georgia

Medical Oncology Associates of Augusta

Augusta, Georgia, United States, 30901

Northeast Georgia Medical Center

Gainesville, Georgia, United States, 30501

United States, Kentucky

Baptist Hospital East

Louisville, Kentucky, United States, 40207

United States, Maryland

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States, 20817

National Capital Clinical Research Consortium

Bethesda, Maryland, United States, 20817

United States, Nebraska

Nebraska Methodist Cancer Center

Omaha, Nebraska, United States, 68114

United States, Ohio

Oncology Hematology Care

Cincinnati, Ohio, United States, 45242

United States, South Carolina

South Carolina Oncology Associates, PA

Columbia, South Carolina, United States, 29210

United States, Tennessee

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States, 37404

Tennessee Oncology, PLLC

Nashville, Tennessee, United States, 37023

United States, Virginia

Virginia Cancer Institute

Richmond, Virginia, United States, 23235

Sponsors and Collaborators

SCRI Development Innovations, LLC

Eli Lilly and Company

Investigators

• Study Chair: David R Spigel, M.D.; SCRI Development Innovations, LLC

More Information

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00906282
• Other Study ID Numbers: SCRI LUN 186
• First Posted: May 21, 2009
• Results First Posted: February 24, 2017
• Last Update Posted: February 24, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by SCRI Development Innovations, LLC:

neoadjuvant NSCLC; NSCLC; pemetrexed

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors