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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

Phase 2
18 Years
Not Enrolling
Non Small Cell Lung Cancer

Thank you

Trial Information

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

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.

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

- 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

- 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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

one year

Safety Issue:


Principal Investigator

Gordana Vlahovic, MD, MHS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

February 2007

Completion Date:

December 2012

Related Keywords:

  • Non Small Cell Lung Cancer
  • genomics
  • genomics predictor
  • genomics analysis
  • squamous
  • non-squamous
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Duke University Medical CenterDurham, North Carolina  27710
Coastal Cancer CenterMyrtle Beach, South Carolina  29572
Community Memorial Health CenterSouth Hill, Virginia  23970-0090
Maria Parham HospitalHenderson, North Carolina  27536
Duke Raleigh HospitalRaleigh, North Carolina  27609
Scotland HealthCare System (Scotland Memorial Hospital)Laurinburg, North Carolina  28352
Southeastern Regional Medical Center, Gibson Cancer CenterLumberton, North Carolina  28358
Beaufort Memorial HospitalBeaufort, South Carolina  29902