Study Using a Genomic Predictor of Platinum Resistance to Guide Therapy in Stage IIIB/IV Non-Small Cell Lung Cancer (TOP0602)

This study has been terminated.
(voluntary closure of trial)
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT00509366
First received: July 30, 2007
Last updated: November 3, 2010
Last verified: November 2010
  Purpose

This study will assign subjects with chemo-naive advanced non-small cell lung cancer (NSCLC) to chemotherapy using a genomic-based predictor to determine platinum sensitivity. Subjects with squamous cell NSCLC who are sensitive to cisplatin will receive cisplatin/gemcitabine and if resistant to cisplatin will receive docetaxel/gemcitabine. Subjects with non-squamous cell NSCLC who are sensitive to cisplatin will receive cisplatin/pemetrexed and if resistant to cisplatin will receive pemetrexed/gemcitabine.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: Cisplatin & Gemcitabine
Drug: Cisplatin & Pemetrexed
Drug: Docetaxel & Gemcitabine
Drug: Pemetrexed & Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Prospective Study Evaluating the Role of Personalized Chemotherapy Regimens for Chemo-Naive Select Stage IIIB and IV Non-Small Cell Lung Cancer (NSCLC) in Patients Using a Genomic Predictor of Platinum Resistance to Guide Therapy

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Observe one year progression free survival in patients with chemo-naive select stage IIIB or stage IV NSCLC whose tumor genomics demonstrates cisplatin-sensitivity versus cisplatin-resistance. [ Time Frame: one year ] [ Designated as safety issue: No ]
  • To further validate the use of a genomics-based model for predicting the patients tumor response to cisplatin. [ Time Frame: three years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progressive disease [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Quality of Life measures utilizing FACT-L and TOI: LCS-assessed symptom improvement and overall QOL. [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Compare drug sensitivity patterns of cisplatin and pemetrexed in both groups. [ Time Frame: three years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: February 2007
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cisplatin Sensitive

Assignment to Treatment Group based on histology and tumor genomics analysis:

Squamous Cell NSCLC-Cisplatin day 1, Gemcitabine days 1 & 8:

Non-Squamous Cell NSCLC-Cisplatin day 1, Pemetrexed day 1

Drug: Cisplatin & Gemcitabine

Squamous Cell NSCLC:

Gemcitabine 1250 mg/m2 IV over 30 minutes day 1 and 8, followed by Cisplatin 75 mg/m2 IV over 60 minutes day 1; repeat every 21 days for up to 6 cycles

Other Name: Gemzar
Drug: Cisplatin & Pemetrexed

Non-Squamous Cell NSCLC:

Pemetrexed 500 mg/m2 IV over approximately 10 minutes day 1, followed by Cisplatin 75 mg/m2 IV over 60 minutes day 1; repeat every 21 days for up to 6 cycles

Other Name: Alimta
Active Comparator: Cisplatin Resistant

Assignment to Treatment Group based on histology and tumor genomics analysis:

Squamous Cell NSCLC-Docetaxel day 1, Gemcitabine days 1 & 8:

Non-Squamous Cell NSCLC-Pemetrexed day 1, Gemcitabine days 1 & 8

Drug: Docetaxel & Gemcitabine

Squamous Cell NSCLC:

Docetaxel 75 mg/m2 IV over 60 minutes day 1, followed by Gemcitabine 1250 mg/m2 IV over 30-60 minutes day 1 and alone day 8; repeat every 21 days for up to 6 cycles

Other Names:
  • Taxotere
  • Gemzar
Drug: Pemetrexed & Gemcitabine

Non-Squamous Cell NSCLC:

Pemetrexed 500 mg/m2 IV over approximately 10 minutes day 1, followed by Gemcitabine 1250 mg/m2 IV over 30-60 minutes day 1 and alone day 8; repeat every 21 days for up to 6 cycles

Other Names:
  • Alimta
  • Gemzar

Detailed Description:

Lung cancer is the leading cause of cancer death in both men and women. The majority of patients with lung cancer have non-small cell type (NSCLC). The current standard of care for treating select stage IIIB and stage IV NSCLC is a doublet chemotherapy regimen, such as cisplatin plus gemcitabine, carboplatin plus paclitaxel, or a platinum agent plus vinorelbine. All of these regimens have comparable response rates as first-line therapy. In addition, the combination of cisplatin plus pemetrexed has recently been approved for non-squamous histology, based on results of a large randomized prospective trial in advanced stage NSCLC. Alternative doublet therapy for first-line treatment of NSCLC per ASCO and NCCN guidelines also include a non-platinum doublet or single agent therapy.

Although platinum agents are routinely used as first-line therapy for advanced NSCLC, interim results in this trial have shown that approximately 40-50% of these patients have disease that is sensitive to platinum agents based on our genomic signature of platinum sensitivity. Of the patients who are resistant to platinum agents, 60% of those patients have disease that is sensitive to pemetrexed. However, this technology is not yet used to guide therapy for individual patients and it is not known how the use of this technology may affect outcomes.

An individual patient's response to chemotherapy is the result of complex interactions between the drug(s) and the patient's genetics and environment. Using Affymetrix gene expression data with corresponding drug response data for cisplatin from the NCI60 lines panel, a robust gene expression based model predicative of cisplatin-resistant has been developed. Based on preclinical observations, a first-line chemotherapy regimen for each patient will be individualized based on histology and gene expression patterns seen in a given patient.

  Eligibility

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

Inclusion Criteria:

  • Suspected or histologic/cytologic select stage IIIB or IV NSCLC, not amenable to curative treatment with surgery or XRT. Histologic/cytologic documentation of recurrence required in patients who were previously completely resected and now have metastatic disease.
  • Fresh frozen tissue must be available to generate and apply the genomics predictor. If not obtained at the time of diagnosis, then subject must consent to another biopsy as a fresh tissue sample must yield adequate high quality RNA. Patients with symptomatic brain metastases must complete brain XRT and be neurologically stable (steroids permitted) prior to research biopsy. If patient had prior XRT therapy, fresh frozen tissue biopsy for genomics analysis must be outside XRT field.
  • At least one, non-radiated, measurable lesion by RECIST criteria.
  • ECOG performance status of 0 or 1.
  • NO prior chemo, biologic or targeted therapy for any malignancy. Prior therapy with low dose methotrexate or similar medications allowed if used for non-malignant conditions.
  • Prior XRT therapy is permitted if ≥1 week since completion of XRT (≥2 weeks for whole brain XRT). XRT must be <25% of bone marrow reserve.
  • Age ≥18 years.
  • No previous or concomitant malignancy in past 5 years other than surgical management for carcinoma in situ of the cervix, breast, NSCLC, basal cell or squamous cell carcinoma of the skin.
  • No other serious medical or psychiatric illness.
  • Signed informed consent.
  • Required lab data within 2 weeks of enrollment:

    1. ANC/AGC ≥1500 per uL
    2. Platelets ≥100,000 per uL
    3. Total bili ≤1.5 mg/dL
    4. Creatinine ≤2 mg/dL; creatinine clearance ≥45 ml/min.
    5. SGOT/SGPT ≤3x ULN except in presence of known hepatic mets (may be up to 5x ULN) unless receive docetaxel/gemcitabine than SGOT/SGPT ≤1.5x ULN.
  • Females of child-bearing potential (not surgically sterilized and between menarche and 1 year post menopause) must test negative for pregnancy within 7 days prior to or at the time of enrollment based on a serum pregnancy test.
  • Both sexually active males and females of reproductive potential must agree to use a reliable method of birth control, as determine by the patient and their health care team, during study and for 3 months following the last dose of study drug.

Exclusion 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.
  • Concurrent administration of any other anti-tumor therapy (see #5 inclusion for exceptions).
  • 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.
  • Untreated CNS metastases unless brain XRT completed and neurologically stable (steroids permitted).
  • Major surgery within 2 weeks of study or other serious concomitant systemic disorders that would compromise the safety of the patient or patient's ability to complete the study.
  • MI having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia or cardiac failure not controlled by meds.
  • Contraindications to corticosteroids.
  • Inability/unwillingness to take folic acid or vitamin B12.
  • 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 treatment initiation and throughout study enrollment.
  • Inability to discontinue aspirin at a dose >1300 mg/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days for long-acting agents such as piroxicam).
  • Female patients that are pregnant or breast-feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509366

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Maria Parham Hospital
Henderson, North Carolina, United States, 27536
Scotland HealthCare System (Scotland Memorial Hospital)
Laurinburg, North Carolina, United States, 28352
Southeastern Regional Medical Center, Gibson Cancer Center
Lumberton, North Carolina, United States, 28358
Duke Raleigh Hospital
Raleigh, North Carolina, United States, 27609
United States, South Carolina
Beaufort Memorial Hospital
Beaufort, South Carolina, United States, 29902
Coastal Cancer Center
Myrtle Beach, South Carolina, United States, 29572
United States, Virginia
Community Memorial Health Center
South Hill, Virginia, United States, 23970
Sponsors and Collaborators
Duke University
Eli Lilly and Company
Investigators
Principal Investigator: Gordana Vlahovic, MD, MHS Duke University
  More Information

Additional Information:
Publications:
Responsible Party: Gordana Vlahovic, MD, MHS, Duke Comprehensive Medical Center
ClinicalTrials.gov Identifier: NCT00509366     History of Changes
Other Study ID Numbers: Pro00004599
Study First Received: July 30, 2007
Last Updated: November 3, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
genomics
genomics predictor
genomics analysis
squamous
non-squamous

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
Gemcitabine
Docetaxel
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 26, 2014