Clinical trial NCT00545948
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
Sponsor: Duke University
Start date: 2007-12-01; Completion date: 2012-01-01
Enrollment: 31 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:
The proposed study is a multi-center open label phase II study of the chemotherapy doublets cisplatin/vinorelbine and cisplatin/pemetrexed as adjuvant therapy in early stage non-squamous NSCLC.

Eligible patients had no previous treatment for the current diagnosis of NSCLC. The two treatment groups of patients will be determined by gene expression profile analysis of each patient's tumor: one group of vinorelbine-sensitive patients and one group of pemetrexed-sensitive patients. The genomic expression profiling that was utilized generated a percentage for likelihood of chemotherapy sensitivity. Patients were directed to receive the chemotherapy regimen for which the percentage of predicted sensitivity is highest. For instance, if the model predicted the likelihood of tumor sensitivity was 46% to vinorelbine and 48% to pemetrexed, then the adjuvant chemotherapy would be directed to cisplatin/pemetrexed. Patients whose tumors could not be adequately analyzed for gene expression were offered adjuvant therapy off protocol as deemed appropriate by their primary oncologist. Patients with either squamous or non-squamous cell histology were eligible to participate in this study as indicated in study protocols dated prior to January 25, 2010. An amendment to the protocol on January 25, 2010 indicated inclusion of only non-squamous histology. However, because of low accrual after January 25, 2010 (5 patients, including 2 screen failures), this report reflects the original study outcomes that includes both squamous and non-squamous histologies.

Thirty-one patients with stage IB (\> 4 cm), II or IIIA non-squamous NSCLC were enrolled, from which 24 were assigned treatment. The vinorelbine-sensitive tumors group received Vinorelbine 25 mg/m2 days 1 and 8, followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. The pemetrexed-sensitive tumors group received pemetrexed 500 mg/m2 day 1 followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. Standard pre-medication regimens included dexamethasone, vitamin B12 and folate supplementation in the pemetrexed group. Patients in both groups will receive up to a maximum of 4 cycles of therapy.

Subsequent reevaluation of the genomic signatures of chemotherapy sensitivity have shown that they were irreproducible, suggesting inaccurate patient assignments into the two treatment arms. As a result, it would be inappropriate to separately analyze outcomes for the different treatment groups. Instead, information from both arms will be combined to reflect the overall measure of two-year progression-free survival in this study. Similarly for secondary objectives, both arms will be combined to address endpoints.

To assess patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer, patients provided responses for the following questions at baseline:

1. Did your doctor talk to you today about choosing chemotherapy treatment for lung cancer based on the genomics of your tumor?
2. How well did you understand what you doctor told you about choosing chemotherapy based on the genomics of your tumor? (circle a number between 1 and 7, where 1 = very poorly and 7 = very well)
3. Do you think the type of chemotherapy that you will get is based on the genomics of your tumor?
4. Do you think you will get better medical care for the treatment of your lung cancer if it is based on the genomics of your tumor?
5. To what extent do you think treating lung cancer based on the genomics of the tumor will lead to more successful treatment strategies? (circle a number between 1 and 7, where 1 = definitely will not lead to a more successful treatment and 7 = definitely will lead to a more successful treatment)
6. How effective do you think chemotherapy will be at stopping your cancer from coming back? (circle a number between 1 and 7, where 1 = not at all effective and 7 = completely effective)
7. To what extent is YOUR lung cancer primarily caused by genetics? (circle a number between 1 and 7, where 1 = not at all caused by genetics and 7 = completely caused by genetics)
8. To what extent to do you think your lung cancer is treatable? (circle a number between 1 and 7, where 1 = definitely not treatable and 7 = definitely treatable)
9. Did your doctor talk to you about your chance of your lung cancer coming back? (Yes - go to question 10, No - go to question 11, Do not know - go to question 11)
10. What did your doctor say was your chance of your cancer coming back? (Low Risk, Moderate or intermediate risk, High risk, Do not know)
11. What do you think is your chance of your lung cancer coming back in the next year on a scale from 1 to 7 where 1=definitely will not come back and 7=definitely will come back?
12. How worried are you that your lung cancer will come back in the next year? (circle a number between 1 and 7, where 1=not at all worried and 7=extremely worried)

Arms: arm 1: Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of vinorelbine sensitivity were given cisplatin + vinorelbine. arm 2: Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of pemetrexed sensitivity were given cisplatin + pemetrexed.
Interventions: intervention 1: Vinorelbine followed by Cisplatin intervention 2: Pemetrexed followed by Cisplatin
Intervention descriptions: intervention 1: 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). intervention 2: 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)

Protocol documents: