- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00226577
Pharmacogenomic & Phase II Study of Gemcitabine and Pemetrexed in Non-Small-Cell Lung Cancer.
Phase II Study of Neoadjuvant Chemotherapy With Gemcitabine and Pemetrexed in Resectable Non-Small-Cell Lung Cancer (NSCLC) With Pharmacogenomic Correlates.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study will evaluate the efficacy and safety of neoadjuvant chemotherapy with gemcitabine and pemetrexed given together 4-times biweekly in patients with resectable NSCLC. All patients will be seen by members of the Thoracic Oncology Program at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and they will be discussed in our weekly multidisciplinary thoracic oncology conference. The conference includes pathologists, radiologists, thoracic surgeons, pulmonologists, radiation oncologists, medical oncologists, oncology nurse specialists, case managers, social workers, and clinical trials coordinators. They will have initial tests as outlined in the study timetable. Patients will receive gemcitabine biweekly on days 1, 15, 29, and 43 at a dose of 1,500 mg/m2. They will also receive pemetrexed at a dose of 500 mg/m2 on days 1, 15, 29, and 43. Gemcitabine will be given first over a period of 30 minutes i.v. followed by pemetrexed over 10 minutes i.v. All patients will get a post induction chemotherapy PET scan, CT scan, and PFT's including a DLCO. They will then go on to thoracotomy including bronchoscopy and mediastinal lymph node dissection between days 64 and 77 if the tumor is deemed completely resectable on restaging studies.
The administration of chemotherapy at the earliest time (neoadjuvant or induction chemotherapy) following diagnosis in an effort to reduce the risk of disease recurrence. This approach also allows for investigations of molecular parameters that may affect response to chemotherapy and patients' survival. It is our hypothesis that the expression of genes associated with activation, inactivation, and efficacy of the drugs gemcitabine and pemetrexed will predict response to therapy and prognosis. We further hypothesize that the expression of these genes will be altered during chemotherapy, and that the global assessment of tumor proliferation, apoptosis, and genome damage is associated with response to therapy. We propose a phase II study of neoadjuvant chemotherapy with gemcitabine and pemetrexed in patients with resectable NSCLC, specifically correlating molecular and genetic parameters to the primary clinical study endpoint disease response (radiographic CR+PR) and the secondary endpoints complete pathological response at surgery, disease-free survival, and overall survival.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center & Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Microscopically confirmed non-small cell carcinoma of the lung, which may be confirmed at the initial bronchoscopy and mediastinoscopy, or by transthoracic needle biopsy.
- No prior therapy for lung cancer.
- Patients must have disease stages IB (T2N0M0), IIA (T1N1M0), IIB (T2N1M0 and T3N0M0), or IIIA (T3N1M0 and T1-3N2M0). Patients with 2 lesions in one lobe (T4) (Stage IIIB) are eligible.
- Patients must be deemed medically fit for surgical resection by a thoracic surgeon.
- Patients must have an ECOG performance status of Zero or One.
- Patients must have measurable or evaluable disease.
- Measurable Disease: Any mass reproducibly measurable in one diameter (RECIST criteria).
- Evaluable disease: Lesions apparent on chest CT, which do not meet the criteria for measurability. These include ill-defined masses associated with post obstructive changes.
- Age >18 years.
- Patient must be able to understand and sign the informed consent.
- Patients must be >12 weeks from prior major surgery, such as a coronary artery bypass graft.
Exclusion Criteria:
- White blood cell count <3000/mm3
- Platelet count <100,000/mm3
- Hemoglobin <9.0 g/dl
- Creatinine >1.5 mg/dl
- Total bilirubin >1.5 mg/dl
- SGOT, SGPT, or AP >1.5 x upper limit of normal
- Metastatic disease (except peribronchial/hilar lymph nodes=N1 and ipsilateral/subcarinal mediastinal lymph nodes=N2) or malignant pleural effusion detected on preoperative evaluation. Non-malignant effusions are cytology negative, are non-bloody, and are transudates. Effusions visible only on CT and not large enough for safe thoracentesis will not result in ineligibility. Exudative effusions, even if cytologically negative are excluded. Pleural fluid is considered exudative if: the ratio of pleural fluid protein to serum protein is >0.5 or the ratio of pleural fluid LDH to serum to serum LDH >0.6 or Pleural fluid LDH is >200 IU/liter. A staging PET scan will be used to exclude patients. If there are multiple areas of FDG uptake outside the area of the primary tumor and the hilar and ipsilateral mediastinal lymph nodes, the patient will be excluded by virtue of having metastatic disease. If however, only one area shows an increase in FDG uptake, the area of concern will need further evaluation such as a biopsy to exclude metastatic disease.
- N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scalene) or T4 primary tumor (malignant pleural effusion or mediastinal invasion) by clinical staging criteria (N3 as seen on CT or PET scan, which may be proven by mediastinoscopy at the investigators discretion).
- Pregnancy.
- Other active malignancy within 2 years with the exceptions of non-melanoma skin cancer and cervical carcinoma in situ.
- Psychologic, familial, sociologic, or geographic conditions, which do not permit biweekly medical follow-up and adherence to the study protocol.
- Prior radiation therapy for any cancer to the thorax.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pre-Surgery Chemotherapy
|
Gemcitabine (GemzarR) 1500 mg/m2
Other Names:
Pemetrexed (AlimtaR) 500 mg/m2
Other Names:
When the chemotherapy treatment is completed, the patient's tumor response will be evaluated by a CT scan, pulmonary function test, and another PET scan between days 50 and 63 (during weeks 8 and 9).
If there is no growth or spread of the cancer on any of these tests, patients will then proceed to have surgery by week 10 to remove the cancer.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Response - Radiographic
Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Number of participants with partial or Complete Response. Complete response (CR) is defined as the total disappearance of all malignant and evaluable clinical evidence of cancer without the development of any new malignant lesions documented on the post chemotherapy chest CT and PET scan. Partial response (PR) (measurable disease only): When compared with pre-treatment measurements, a reduction of >30% in the sum of the largest diameters of all measurable lesions and absence of new lesions. |
06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Response - Pathologic
Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Number of participants with Pathologic Complete Response.
Pathologic complete response (pCR) is defined by a surgical pathology specimen, which consists of equal to or more than 95% fibrosis and necrosis.
|
06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Survival - Disease Free
Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Disease-free survival (DFS) is defined as the period of time from surgery to the time when disease recurrence is clearly documented.
A histologic confirmation is required in equivalent cases.
|
06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Survival - Overall
Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Median range of number of participants with Overall Survival.
Overall survival (OS) will be defined as the period of time from the first day of drug treatment to the date of death of the patient.
Patients taken off study will be followed quarterly until death for survival data.
|
06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Toxicity
Time Frame: 06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Number of participants with toxicity ≥ Grade 3 after gemcitabine plus pemetrexed induction chemotherapy.
|
06/20/2008 Index date for patients enrolled between 04/2004 and 04/2006
|
Collaborators and Investigators
Investigators
- Principal Investigator: Gerold Bepler, M.D, Ph.D., H. Lee Moffitt Cancer Center (now at Karmanos Cancer Institute)
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Folic Acid Antagonists
- Gemcitabine
- Pemetrexed
Other Study ID Numbers
- MCC-13726
- H3E-US-X009 (Other Identifier: Eli Lilly & Company)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lung Cancer
-
M.D. Anderson Cancer CenterRecruitingStage III Lung Cancer AJCC v8 | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer... and other conditionsUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingStage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
Dana-Farber Cancer InstituteMedWaves, IncNot yet recruitingLung Cancer | Lung Cancer Stage I | Lung Cancer Stage II | Stage I Lung Cancer | Stage I - II Primary Lung Cancer | Stage II Lung CancerUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingCaregiver | Stage III Lung Cancer AJCC v7 | Stage I Lung Cancer AJCC v7 | Stage II Lung Cancer AJCC v7 | Stage IB Lung Cancer AJCC v7 | Stage IA Lung Cancer AJCC v7 | Stage IIA Lung Cancer AJCC v7 | Stage IIB Lung Cancer AJCC v7 | Stage IIIA Lung Cancer AJCC v7 | Stage IIIB Lung Cancer AJCC v7United States
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Genentech, Inc.RecruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Lung Non-Small Cell Carcinoma | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung... and other conditionsUnited States
-
Emory UniversityNational Cancer Institute (NCI)TerminatedLung Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
University of California, San FranciscoMerck Sharp & Dohme LLCWithdrawnLung Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Metastatic Lung Carcinoma | Stage IV Lung Cancer AJCC v8 | Head and Neck Carcinoma | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung... and other conditionsUnited States
Clinical Trials on Gemcitabine
-
AstraZenecaRecruitingBiliary Tract CancerFrance, Spain, Italy, Korea, Republic of, Japan, Germany, United States, Singapore
-
Sierra Oncology LLC - a GSK companyCompletedAdvanced Solid TumorsSpain, United Kingdom
-
University of Erlangen-Nürnberg Medical SchoolCompleted
-
Shenzhen University General HospitalNot yet recruiting
-
3D Medicines (Sichuan) Co., Ltd.Not yet recruitingBiliary Tract Neoplasms
-
Kansai Hepatobiliary Oncology GroupCompleted
-
Fifth Affiliated Hospital, Sun Yat-Sen UniversityRecruiting
-
3D Medicines (Sichuan) Co., Ltd.RecruitingBiliary Tract NeoplasmsChina
-
Yung NAQueen Mary Hospital, Hong Kong; Pamela Youde Nethersole Eastern HospitalRecruitingMuscle-Invasive Bladder Carcinoma | Muscle Invasive Bladder Urothelial CarcinomaHong Kong
-
Air Force Military Medical University, ChinaRecruiting