Carcinoma, Non-Small-Cell Lung Clinical Trial
Official title:
Phase II Prospective Study Evaluating the Role of Directed Cisplatin Based Chemo With Either Vinorelbine or Pemetrexed for the Adj Tx of Early Stage NSCLC in Patients Using Genomic Expression Profiles of Chemo Sensitivity to Guide Therapy
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.
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)
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Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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