Individualized Therapy Based of Tumoral mRNA Levels of ERCC1, RRM1 and BRCA1 in Advanced Non-Small-Cell Lung Cancer

This study has been terminated.
(Due to poor accrual)
Sponsor:
Collaborator:
University Hospital of Crete
Information provided by (Responsible Party):
Hellenic Oncology Research Group
ClinicalTrials.gov Identifier:
NCT00705549
First received: June 25, 2008
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

This is a prospective pilot phase II trial, in patients with wet stage IIIb and IV NSCLC using chemotherapy regimens which will be defined according to the pharmacogenomic profile (tumoral expression of ERCC1, BRCA1 and RRM1) of the tumor cells.


Condition Intervention Phase
Non-Small-Cell Lung Cancer
Drug: Gemcitabine
Drug: Cisplatin
Drug: Docetaxel
Drug: Vinorelbine
Drug: Pemetrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy Based of Tumoral mRNA Levels of ERCC1, RRM1 and BRCA1 in Advanced Non-Small-Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Hellenic Oncology Research Group:

Primary Outcome Measures:
  • Objective Response Rate (ORR) based on the pharmacogenomic profile of the ERCC1, RRM1 and BRCA1 expression [ Time Frame: Objective responses confirmed by CT or MRI ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the incidence of the different pharmacogenomic profiles as defined by the combined expression of ERCC1, RRM1 and BCRA1 [ Time Frame: Comparison of molecular determinants for response in the primary tumor and peripheral blood (ERCC1 polymorphism ,TXR1 and TSP1 mRNA expression by Q-RT-PCR, Molecular markers related to responsiveness to Alimta ) ] [ Designated as safety issue: No ]
  • Time to Tumor Progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Toxicity assessment on each chemotherapy cycles ] [ Designated as safety issue: Yes ]

Enrollment: 88
Study Start Date: February 2008
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Gemzar/Cisplatin
Drug: Gemcitabine
Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8
Other Name: Gemzar
Drug: Cisplatin
Cisplatin I.V at the dose of 75mg/m2 on Day 1
Other Name: CDDP
Experimental: 2
Taxotere/Cisplatin
Drug: Cisplatin
Cisplatin I.V at the dose of 75mg/m2 on Day 1
Other Name: CDDP
Drug: Docetaxel
Docetaxel I.V at the dose of 75mg/m2 on Day 1
Other Name: Taxotere
Experimental: 3
Cisplatin/Navelbine metronomic
Drug: Cisplatin
Cisplatin I.V at the dose of 80mg/m2 on Day 1
Other Name: CDDP
Drug: Vinorelbine
Vinorelbine per os 50mg every Monday, Wednesday and Friday
Other Name: Navelbine
Experimental: 4
Taxotere/Gemzar
Drug: Gemcitabine
Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8
Other Name: Gemzar
Drug: Docetaxel
Docetaxel I.V at the dose of 75mg/m2 on Day 1
Other Name: Taxotere
Experimental: 5
Gemzar
Drug: Gemcitabine
Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8
Other Name: Gemzar
Experimental: 6
Taxotere
Drug: Docetaxel
Docetaxel I.V at the dose of 75mg/m2 on Day 1
Other Name: Taxotere
Experimental: 7
Navelbine metronomic
Drug: Vinorelbine
Vinorelbine per os 50mg every Monday, Wednesday and Friday
Other Name: Navelbine
Experimental: 8
Alimta/Cisplatin
Drug: Cisplatin
Cisplatin I.V at the dose of 75mg/m2 on Day 1
Other Name: CDDP
Drug: Pemetrexate
Pemetrexate I.V 500mg/m2 on Day 1
Other Name: Alimta
Experimental: 9
Alimta/Gemzar
Drug: Gemcitabine
Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8
Other Name: Gemzar
Drug: Pemetrexate
Pemetrexate I.V 500mg/m2 on Day 1
Other Name: Alimta
Experimental: 10
Taxotere
Drug: Docetaxel
Docetaxel I.V at the dose of 75mg/m2 on Day 1
Other Name: Taxotere
Experimental: 11
Alimta
Drug: Pemetrexate
Pemetrexate I.V 500mg/m2 on Day 1
Other Name: Alimta

Detailed Description:

Advanced stage NSCLC is essentially a fatal disease and treatment is mainly palliative. Systemic cisplatin-based chemotherapy remains the mainstream for the treatment of advanced non-small cell lung cancer (NSCLC) since it improves survival, symptom control and quality of life compared to best supportive care.

The selection of appropriate treatment for individual patients remains a challenge in clinical oncology, particularly in the advanced disease. Several lines of evidence indicate that polymorphisms, gene transcripts and gene mutations can play a predictive role and can be used to tailor chemotherapy in different subgroups of cancer patients. There are evidence lead us to use the expression levels of ERCC1 by the tumor as a molecular marker for customized chemotherapy. Another gene, the BRCA1 has a crucial role in DNA repair, since it is implicated in transcription-coupled nucleotide excision repair (TC-NER), leading to radio- and chemo-resistance. RRM1,localized in 11p15.5,also acts as a putative tumor suppressor gene. RRM1 overexpression was related to gemcitabine resistance in human oropharyngeal epidermoid carcinoma KB cells as well as in patients with NSCLC. For those reason we decided to conduct a prospective pilot phase II trial, in patients with wet stage IIIb and IV NSCLC using chemotherapy regimens which will be defined according to the pharmacogenomic profile (tumoral expression of ERCC1, BRCA1 and RRM1) of the tumor cells.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically proven Stage IV and Stage III (with malignant pleural or pericardial effusion) squamous or adenocarcinoma carcinomas of the lung
  • Adequate Formalin Fixed Paraffin Embedded tumor sample provided for molecular analysis
  • No previous anticancer treatment for metastatic/advanced disease. Patients who received prior adjuvant chemotherapy are eligible if they have remained free of disease for at least 6 months after the completion of adjuvant therapy.
  • Age above 18 years
  • Performance status (ECOG) 0-2
  • Life expectancy >= 3 months
  • Effective contraception for both male and female subjects if the risk of conception exists
  • Adequate hematologic parameters (absolute neutrophil count >= 1.5x109/L and platelets >= 100x109/L), creatinine (GFR>= 60ml/min) and total bilirubin < 1.5 times the upper limit of normal; aspartate and alanine aminotransferase < 2,5 times the upper limit of normal
  • All patients will have to sign written informed consent in order to participate in the study

Exclusion Criteria:

  • Patients with non-squamous tumors who have no contradiction for administration of bevacizumab
  • Active infection or malnutrition (loss of more than 20% of the body weight)
  • Known hypersensitivity reaction to any of the component of the treatment
  • Concurrent or previous chronic systemic immune therapy
  • Pregnancy (absence to be confirmed by ß-HCG test) or lactation period
  • Known alcohol/drug abuse
  • Legal incapacity or limited legal capacity
  • Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent
  • A second primary tumor other than non-melanoma skin cancer or in situ cervical carcinoma
  • Previous radiotherapy to the target lesions. Patients treated with palliative radiotherapy had to have measurable metastatic disease outside the irradiation fields
  • Patients with severe cardiac dysfunction, unstable angina petrosis, or high risk of uncontrolled arrhythmia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705549

Locations
Greece
University General Hospital of Alexandroupolis, Dept. of Medical Oncology
Alexandroupolis, Greece
Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases
Athens, Greece
IASO" General Hospital of Athens, 1st Dep of Medical Oncology
Athens, Greece
Sotiria" General Hospital, 1st, 3rd, 8th Dep of Pulmonary Diseases
Athens, Greece
"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
Athens, Greece
401 Military Hospital, Medical Oncology Unit
Athens, Greece
Air Forces Military Hospital, Dep of Medical Oncology
Athens, Greece
"Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology
Piraeus, Greece
"Theagenion" Anticancer Hospital of Thessaloniki
Thessaloniki, Greece
Sponsors and Collaborators
Hellenic Oncology Research Group
University Hospital of Crete
Investigators
Principal Investigator: John Souglakos, MD University Hospital of Crete, Dep of Medical Oncology
  More Information

No publications provided

Responsible Party: Hellenic Oncology Research Group
ClinicalTrials.gov Identifier: NCT00705549     History of Changes
Other Study ID Numbers: CT/07.23
Study First Received: June 25, 2008
Last Updated: February 12, 2013
Health Authority: Greece: National Organization of Medicines

Keywords provided by Hellenic Oncology Research Group:
Advanced
NSCLC
ERCC1
RRM1
BCRA1
Alimta
Gemcitabine

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Vinorelbine
Docetaxel
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Phytogenic
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 28, 2014