Adjuvant Cisplatin With Either Genomic-Guided Vinorelbine or Pemetrexed for Early Stage Non-Small-Cell Lung Cancer

NCT00545948 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro00000657
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 13

Brief Summary

This study assigned subjects to either cisplatin/vinorelbine or cisplatin/pemetrexed chemotherapy using a genomic based expression profile to determine chemotherapy sensitivity in completely resected early stage non-squamous non-small-cell lung cancer (NSCLC). The vinorelbine-sensitive tumors group received Vinorelbine followed by cisplatin, while the pemetrexed-sensitive tumors group received pemetrexed followed by cisplatin. The primary objective of this trial was to determine whether genomic-based adjuvant chemotherapy treatment increased the 2-year progression-free survival rate in completely resected patients with NSCLC compared to historic controls. Secondary objectives included: 1) estimation of the percentage of completely resected NSCLC tumors that can be adequately analyzed and used to direct specific adjuvant chemotherapy; 2) estimation of the proportion of patients who are assigned to treatment with vinorelbine and pemetrexed; 3) evaluation of drug sensitivity patterns of cisplatin and pemetrexed in both treatment arms; 4) description of the overall median survival experience of treated patients; and 5) assessment of patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-Small-Cell Lung Cancer; NSCLC; Non-Squamous; Genomics; Guided Therapy; Directed Therapy; Genomic Expression Profiles; Chemotherapy Sensitivity

Outcome Measures

Primary Outcomes (1)

• 2-Year Progression-Free Survival Rate in Patients With Completely Resected Stage IB, II, or IIIA NSCLC

  Progression-free survival time was defined as the time from initiation of study treatment to the first date of disease progression or death as a result of any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Time was censored at the date of the last follow-up visit for patients who were still alive and have not progressed. The two-year progression free survival rate is a percentage, representing the fraction of treated patients who, after two years, are disease free or alive.

  2 years

Secondary Outcomes (4)

• Percentage of Patients With Completely Resected NSCLC Tumors That Can Be Analyzed and Used to Direct Adjuvant Chemotherapy

  4 years

• 2-Year Overall Survival in Patients Treated for NSCLC

  2 years

• Patient Understanding and Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for Adjuvant Treatment of Early Stage Lung Cancer

  Baseline

• Compare Drug Sensitivity Patterns of Cisplatin and Pemetrexed in Both Treatment Arms

  2 years

Study Arms (2)

Arm A-Vinorelbine

OTHER

Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of vinorelbine sensitivity were given cisplatin + vinorelbine.

Drug: Vinorelbine followed by Cisplatin

Arm B-Pemetrexed

OTHER

Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of pemetrexed sensitivity were given cisplatin + pemetrexed.

Drug: Pemetrexed followed by Cisplatin

Interventions

Vinorelbine followed by Cisplatin DRUG

Vinorelbine 25 mg/m2 IV over 6-10 minutes on days 1 and 8, followed by Cisplatin 75 mg/m2 IV over 60 minutes on day 1 (every 21 days x 4 cycles).

Also known as: Navelbine, Platinol

Arm A-Vinorelbine

Pemetrexed followed by Cisplatin DRUG

Pemetrexed 500 mg/m2 IV infusion over approximately 10 minutes on day 1, followed by Cisplatin 75 mg/m2 IV over 60 min on day 1 (every 21 days x 4 cycles)

Also known as: Alimta, Platinol

Arm B-Pemetrexed

Eligibility Criteria

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

You may qualify if:

• Patients are eligible to be included in the study only if they meet all of the following criteria:
• Patients with completely resected stage IB (\> 4 cm), II, or IIIA Non-Squamous NSCLC. Patient must be enrolled and begin therapy within 4 to 12 weeks from the date of complete surgical resection.
• Fresh tissue must be available for genomics expression profiling.
• ECOG performance status of 0 or 1.
• NO prior chemotherapy, radiation therapy, or biologic/targeted therapy within the last 5 years. Prior therapy with low dose methotrexate or similar medications is allowed if therapy used to treat non-malignant conditions.
• Age ≥ 18 years.
• No previous or concomitant malignancy in the past 5 years other than curatively-treated carcinoma in situ of the cervix, or basal cell or squamous cell carcinoma of the skin.
• No other serious medical or psychiatric illness.
• Signed informed consent.
• Required laboratory data within one week of enrollment:
• ANC or AGC ≥ 1500 per uL;
• Platelets ≥ 100,000 per uL;
• Total bilirubin ≤ 1.5 mg/dL;
• Creatinine ≤ 2 mg/dL; creatinine clearance ≥ 45 mL/min;
• SGOT/SGPT ≤ 1.5x ULN.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Inability to comply with protocol or study procedures.
• Active infection requiring IV antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant systemic disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
• Contraindication to corticosteroids.
• Inability or unwillingness to take folic acid or vitamin B12 supplementation.
• Unwillingness to stop taking herbal supplements while on study.
• Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry and throughout study enrollment as the distribution of pemetrexed in this fluid space is not fully understood.
• Inability to discontinue administration of aspirin at a dose \> 1300 mg/day or other long acting, non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam). Moderate dose ibuprofen may be continued.
• Female patients that are pregnant or breast-feeding.

Sponsors & Collaborators

• Duke University: lead
• Eli Lilly and Company: collaborator

Study Sites (13)

Palm Beach Cancer Institute

West Palm Beach, Florida, 33401, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Presbyterian HealthCare

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Maria Parham Hospital

Henderson, North Carolina, 27536, United States

Location

Scotland HealthCare System (Scotland Memorial Hospital)

Laurinburg, North Carolina, 28352, United States

Location

Southeastern Regional Medical Center, Gibson Cancer Center

Lumberton, North Carolina, 28358, United States

Location

Duke Raleigh Hospital

Raleigh, North Carolina, 27609, United States

Location

Johnston Memorial Hospital Authority

Smithfield, North Carolina, 27577, United States

Location

Columbus County Hospital

Whiteville, North Carolina, 28472, United States

Location

Beaufort Memorial Hospital

Beaufort, South Carolina, 29902, United States

Location

Coastal Cancer Center

Myrtle Beach, South Carolina, 29572, United States

Location

Community Memorial Health Center

South Hill, Virginia, 23970, United States

Location

Related Publications (2)

• Potti A, Mukherjee S, Petersen R, Dressman HK, Bild A, Koontz J, Kratzke R, Watson MA, Kelley M, Ginsburg GS, West M, Harpole DH Jr, Nevins JR. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med. 2006 Aug 10;355(6):570-80. doi: 10.1056/NEJMoa060467.

  PMID: 16899777 BACKGROUND

• Potti A, Dressman HK, Bild A, Riedel RF, Chan G, Sayer R, Cragun J, Cottrill H, Kelley MJ, Petersen R, Harpole D, Marks J, Berchuck A, Ginsburg GS, Febbo P, Lancaster J, Nevins JR. Genomic signatures to guide the use of chemotherapeutics. Nat Med. 2006 Nov;12(11):1294-300. doi: 10.1038/nm1491. Epub 2006 Oct 22.

  PMID: 17057710 BACKGROUND

Related Links

• Clinical Trials at Duke Cancer Institute

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Vinorelbine; Cisplatin; Pemetrexed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Neal Ready, PhD, MD
• Organization: Duke University Medical Center

neal.ready@duke.edu

919-681-6932

Study Officials

• Neal Ready, Ph.D., M.D.

  Duke University Medical Center, Hematology/Oncology, Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 18, 2007
• Study Start: December 1, 2007
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: July 21, 2014
• Results First Posted: June 9, 2014

Record last verified: 2014-06

Locations

US (13)