Carcinoma, Non-Small-Cell Lung Clinical Trial
— TOP0703Official 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
Verified date | June 2014 |
Source | Duke University |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Institutional Review Board |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 31 |
Est. completion date | January 2012 |
Est. primary completion date | January 2012 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: 1. Patients with completely resected stage IB (> 4 cm), II, or IIIA Non-Squamous NSCLC. Patient must be enrolled and begin therapy within 4 to 12 weeks from the date of complete surgical resection. 2. Fresh tissue must be available for genomics expression profiling. 3. ECOG performance status of 0 or 1. 4. NO prior chemotherapy, radiation therapy, or biologic/targeted therapy within the last 5 years. Prior therapy with low dose methotrexate or similar medications is allowed if therapy used to treat non-malignant conditions. 5. Age = 18 years. 6. No previous or concomitant malignancy in the past 5 years other than curatively-treated carcinoma in situ of the cervix, or basal cell or squamous cell carcinoma of the skin. 7. No other serious medical or psychiatric illness. 8. Signed informed consent. 9. Required laboratory data within one week of enrollment: - ANC or AGC = 1500 per uL; - Platelets = 100,000 per uL; - Total bilirubin = 1.5 mg/dL; - Creatinine = 2 mg/dL; creatinine clearance = 45 mL/min; - SGOT/SGPT = 1.5x ULN. 10. 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 determined by the patient and their health care team, during the study and for 3 months following the last dose of study drug. Exclusion Criteria: Patients will be excluded from the study if they meet any of the following criteria: 1. Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. 2. Concurrent administration of any other anti-tumor therapy (see #4 inclusion for exceptions). 3. Inability to comply with protocol or study procedures. 4. 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. 5. Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant systemic disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study. 6. Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications. 7. Contraindication to corticosteroids. 8. Inability or unwillingness to take folic acid or vitamin B12 supplementation. 9. Unwillingness to stop taking herbal supplements while on study. 10. 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 study entry and throughout study enrollment as the distribution of pemetrexed in this fluid space is not fully understood. 11. Inability to discontinue administration of aspirin at a dose > 1300 mg/day or other long acting, non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam). Moderate dose ibuprofen may be continued. 12. Female patients that are pregnant or breast-feeding. |
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Beaufort Memorial Hospital | Beaufort | South Carolina |
United States | Presbyterian HealthCare | Charlotte | North Carolina |
United States | University of Chicago Medical Center | Chicago | Illinois |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Maria Parham Hospital | Henderson | North Carolina |
United States | Scotland HealthCare System (Scotland Memorial Hospital) | Laurinburg | North Carolina |
United States | Southeastern Regional Medical Center, Gibson Cancer Center | Lumberton | North Carolina |
United States | Coastal Cancer Center | Myrtle Beach | South Carolina |
United States | Duke Raleigh Hospital | Raleigh | North Carolina |
United States | Johnston Memorial Hospital Authority | Smithfield | North Carolina |
United States | Community Memorial Health Center | South Hill | Virginia |
United States | Palm Beach Cancer Institute | West Palm Beach | Florida |
United States | Columbus County Hospital | Whiteville | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Duke University | Eli Lilly and Company |
United States,
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. Epub 2006 Oct 22. Erratum in: Nat Med. 2007 Nov;13(11):1388. Nat Med. 2008 Aug;14(8):889. Retraction in: 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. Nat Med. 2011 Jan;17(1):135. — View Citation
Potti A, Mukherjee S, Petersen R, Dressman HK, Bild A, Koontz J, Kratzke R, Watson MA, Kelley M, Ginsburg GS, West M, Harpole DH Jr, Nevins JR. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med. 2006 Aug 10;355(6):570-80. Erratum in: N Engl J Med. 2007 Jan 11;356(2):201-2. Retraction in: Potti A, Mukherjee S, Petersen R, Dressman HK, Bild A, Koontz J, Kratzke R, Watson MA, Kelley M, Ginsburg GS, West M, Harpole DH Jr, Nevins JR. N Engl J Med. 2011 Mar 24;364(12):1176. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 2-Year Progression-Free Survival Rate in Patients With Completely Resected Stage IB, II, or IIIA NSCLC | Progression-free survival time was defined as 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 two-year progression free survival rate is a percentage, representing the fraction of treated patients who, after two years, are disease free or alive. | 2 years | No |
Secondary | Percentage of Patients With Completely Resected NSCLC Tumors That Can Be Analyzed and Used to Direct Adjuvant Chemotherapy | The percentage of patients with completely resected NSCLC tumors who had successful genomic analysis and assigned to treatment among patients. All 31 patients enrolled in the study had completely resected tumors. These tumors included a mixture of squamous and non-squamous histologies as indicated the original protocol. However, an amendment dated January 25, 2010 limited eligibility to patients with non-squamous disease. Given that only 5 patients were accrued into the study after this amendment, results reported will consider all histologies. | 4 years | No |
Secondary | 2-Year Overall Survival in Patients Treated for NSCLC | Overall survival time was defined as the time from initiation of study treatment to the date of death as a result of any cause. Time was censored at the date of the last follow-up visit for patients who were still alive. The two-year overall survival rate is a percentage, representing the fraction of treated patients who, after two years, are alive | 2 years | No |
Secondary | Patient Understanding and Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for Adjuvant Treatment of Early Stage Lung Cancer | Do to space limitations, see the Detailed Description in the study protocol for the wording of the questions used in the Patient Expectations Questionnaire. | Baseline | No |
Secondary | Compare Drug Sensitivity Patterns of Cisplatin and Pemetrexed in Both Treatment Arms | Using genomics-based prediction models previously developed separately for cisplatin and pemetrexed, the probability that each patient was sensitive or would respond to treatment was computed. Quartiles describe the patterns of drug sensitivity probabilities. The 1st, 2nd, and 3rd quartiles are the sensitivity levels at which 25%, 50%, and 75% of patients have lower sensitivity. There is lack of integrity regarding the available data due to irreproducible genomic signatures. Therefore the results of this outcome are not presented. | 2 years | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04879849 -
A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers
|
Phase 1 | |
Completed |
NCT04426825 -
A Study of Atezolizumab in Combination With Bevacizumab in Patients With EGFR Mutation Positive Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer
|
Phase 2 | |
Terminated |
NCT03166631 -
A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread
|
Phase 1 | |
Completed |
NCT02810457 -
Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer
|
Phase 3 | |
Completed |
NCT02864394 -
Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)
|
Phase 3 | |
Recruiting |
NCT04592523 -
A Study of Usage of Brigatinib in the Treatment of Adult Participants for Approved Indications In South Korea
|
||
Recruiting |
NCT04838548 -
A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With EGFR-Positive Advanced Non-Small Cell Lung Cancer
|
Phase 2 | |
Recruiting |
NCT04077463 -
A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer
|
Phase 1 | |
Recruiting |
NCT05167604 -
Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC
|
||
Recruiting |
NCT04603807 -
A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases
|
Phase 3 | |
Completed |
NCT04948411 -
Durvalumab as Maintenance in Patients Who Received Chemoradiotherapy for Unresectable Stage III NSCLC: Real World Data From an Expanded Access Program in Brazil
|
||
Active, not recruiting |
NCT04487080 -
A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
|
Phase 3 | |
Not yet recruiting |
NCT04255836 -
Durvalumab Combined With Chemotherapy and Stereotactic Body Radiotherapy (SBRT) in Patients With Oligometastatic Non-small Cell Lung Cancer (NSCLC)
|
Phase 2 | |
Completed |
NCT01953913 -
Afatinib (BIBW 2992) in Advanced Non-Small Cell Lung Cancer Patients With EGFR Mutation
|
Phase 3 | |
Recruiting |
NCT05715229 -
Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy
|
Phase 2 | |
Recruiting |
NCT04931654 -
A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer
|
Phase 1/Phase 2 | |
Suspended |
NCT05421936 -
Osimertinib for NSCLC With Uncommon EGFR Mutations
|
||
Completed |
NCT02847377 -
A Positron Emission Tomography (PET) Imaging Agent [18F]-ODS2004436 as a Marker of EGFR Mutation in Subjects With NSCLC
|
N/A | |
Completed |
NCT04427072 -
Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
|
Phase 3 | |
Recruiting |
NCT04823377 -
Impact of a Process Optimizing the Decision to Continue or Stop Cancer Treatments in Patients With Advanced Non-small Cell Lung Cancer.
|
N/A |