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

NCT00509366 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro00004599
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 8

Brief Summary

In this trial, subjects with chemo-naive advanced non-small cell lung cancer (NSCLC) were assigned to chemotherapy using a genomic-based predictor for platinum sensitivity. After an amendment dated 1/25/2010, subjects with squamous cell NSCLC sensitive to cisplatin received cisplatin/gemcitabine and if resistant to cisplatin received docetaxel/gemcitabine. Subjects with non-squamous cell NSCLC sensitive to cisplatin received cisplatin/pemetrexed and if resistant to cisplatin received pemetrexed/gemcitabine. The primary objective of this trial was to prospectively validate the genomic-based prediction model through separate evaluation of the one-year progression-free survival (PFS) of the cisplatin-sensitive and cisplatin-resistant cohorts. Secondary objectives included: assessment of overall time to progressive disease, quality of life and evaluation of drug sensitivity patterns of cisplatin and pemetrexed.

Conditions

Non Small Cell Lung Cancer

Keywords

genomics; genomics predictor; genomics analysis; squamous; non-squamous

Outcome Measures

Primary Outcomes (1)

• 1-year Progression Free Survival Rate in Chemo-naive Select Stage IIIB or Stage IV NSCLC Patients

  One-year progression-free survival was defined from 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 one-year progression free survival rate is a percentage, representing the fraction of treated patients who, after one-year, are disease free or alive.

  1 year

Secondary Outcomes (3)

• Median Time to Progressive Disease

  1 Year

• Mean Change From Baseline to Follow-up Cycle in Quality of Life - Functional Assessment of Cancer Therapy-Lung (FACT-L)

  Baseline, Every 21 days for a maximum of 6 cycles

• Drug Sensitivity Quartiles for Cisplatin and Pemetrexed

  3 years

Study Arms (4)

Cisplatin Sensitive (Post-Amendment)

ACTIVE COMPARATOR

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 Per an amendment dated 1/25/2010, post-amendment treatment assignment refers to the further separation of patients into sub-groups, within the cisplatin sensitive arm, based on histology (squamous/non-squamous).

Drug: Cisplatin & Gemcitabine; Drug: Cisplatin & Pemetrexed

Cisplatin Resistant (Post-Amendment)

ACTIVE COMPARATOR

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 Per an amendment dated 1/25/2010, post-amendment treatment assignment refers to the further separation of patients into sub-groups, within the cisplatin resistant arm, based on histology (squamous/non-squamous).

Drug: Docetaxel & Gemcitabine; Drug: Pemetrexed & Gemcitabine

Cisplatin Sensitive (Pre-Amendment)

ACTIVE COMPARATOR

Assignment to Treatment Group based on tumor genomics analysis: Cisplatin day 1, Gemcitabine days 1 \& 8

Drug: Cisplatin & Gemcitabine

Cisplatin Resistant (Pre-Amendment)

ACTIVE COMPARATOR

Assignment to Treatment Group based on tumor genomics analysis: Pemetrexed day 1, Gemcitabine days 1 \& 8

Drug: Pemetrexed & Gemcitabine

Interventions

Cisplatin & Gemcitabine DRUG

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

Also known as: Gemzar

Cisplatin Sensitive (Post-Amendment); Cisplatin Sensitive (Pre-Amendment)

Cisplatin & Pemetrexed DRUG

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

Also known as: Alimta

Cisplatin Sensitive (Post-Amendment)

Docetaxel & Gemcitabine DRUG

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

Also known as: Taxotere, Gemzar

Cisplatin Resistant (Post-Amendment)

Pemetrexed & Gemcitabine DRUG

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

Also known as: Alimta, Gemzar

Cisplatin Resistant (Post-Amendment); Cisplatin Resistant (Pre-Amendment)

Eligibility Criteria

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

You may qualify if:

• 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:
• ANC/AGC ≥1500 per uL
• Platelets ≥100,000 per uL
• Total bili ≤1.5 mg/dL
• Creatinine ≤2 mg/dL; creatinine clearance ≥45 ml/min.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

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

Study Sites (8)

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

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, 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

• Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, Olson JA Jr, Marks JR, Dressman HK, West M, Nevins JR. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2006 Jan 19;439(7074):353-7. doi: 10.1038/nature04296. Epub 2005 Nov 6.

  PMID: 16273092 BACKGROUND

Related Links

• Clinical Trials at Duke Comprehensive Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Gemcitabine; Pemetrexed; Docetaxel

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)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The microarray-based prediction model of chemotherapy sensitivity, used to allocate patients into the cisplatin treatment arms, was irreproducible and inaccurate. Quality of life measurements were incomplete and could not be analyzed.

Results Point of Contact

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

neal.ready@duke.edu

919-681-6932

Study Officials

• Gordana Vlahovic, MD, MHS

  Duke University

  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: July 30, 2007
• First Posted: July 31, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: August 28, 2014
• Results First Posted: August 28, 2014

Record last verified: 2014-08

Locations

US (8)