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

Sponsors and Collaborators:	Hellenic Oncology Research Group University Hospital of Crete
Information provided by:	Hellenic Oncology Research Group
ClinicalTrials.gov Identifier:	NCT00705549

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 II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Vinorelbine Gemcitabine Docetaxel Gemcitabine hydrochloride Vinorelbine tartrate Pemetrexed disodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

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 ]

Estimated Enrollment:	100
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Gemzar/Cisplatin	Drug: Gemcitabine Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8 Drug: Cisplatin Cisplatin I.V at the dose of 75mg/m2 on Day 1
2: Experimental Taxotere/Cisplatin	Drug: Cisplatin Cisplatin I.V at the dose of 75mg/m2 on Day 1 Drug: Docetaxel Docetaxel I.V at the dose of 75mg/m2 on Day 1
3: Experimental Cisplatin/Navelbine metronomic	Drug: Cisplatin Cisplatin I.V at the dose of 80mg/m2 on Day 1 Drug: Vinorelbine Vinorelbine per os 50mg every Monday, Wednesday and Friday
4: Experimental Taxotere/Gemzar	Drug: Gemcitabine Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8 Drug: Docetaxel Docetaxel I.V at the dose of 75mg/m2 on Day 1
5: Experimental Gemzar	Drug: Gemcitabine Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8
6: Experimental Taxotere	Drug: Docetaxel Docetaxel I.V at the dose of 75mg/m2 on Day 1
7: Experimental Navelbine metronomic	Drug: Vinorelbine Vinorelbine per os 50mg every Monday, Wednesday and Friday
8: Experimental Alimta/Cisplatin	Drug: Cisplatin Cisplatin I.V at the dose of 75mg/m2 on Day 1 Drug: Pemetrexate Pemetrexate I.V 500mg/m2 on Day 1
9: Experimental Alimta/Gemzar	Drug: Gemcitabine Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8 Drug: Pemetrexate Pemetrexate I.V 500mg/m2 on Day 1
10: Experimental Taxotere	Drug: Docetaxel Docetaxel I.V at the dose of 75mg/m2 on Day 1
11: Experimental Alimta	Drug: Pemetrexate Pemetrexate I.V 500mg/m2 on Day 1

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

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

Contacts

Contact: Dora Hatzidaki	+302810392570	dorachat@med@uoc.gr
Contact: Eva Maragkoudaki	+302810392857	dorachat@med.uoc.gr

Locations

Greece
Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases	Recruiting
Athens, Greece
Contact: Nikoleta Karkatzou, MD 30-21-0644-8666 secretary@horg.gr
Contact: Spyros Georgiadis 30-21-0645-7968 secretary@horg.gr
Principal Investigator: Maria Agelidou, MD
Principal Investigator: Vassilis Xandrinos, MD
University General Hospital of Alexandroupolis, Dept. of Medical Oncology	Recruiting
Alexandroupolis, Greece
Contact: Dora Hatzidaki +302810392570 dorachat@med.uoc.gr
Contact: Eva Maragkoudaki +30281392857 dorachat@med.uoc.gr
Principal Investigator: Stelios Kakolyris, MD
IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Recruiting
Athens, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Stelios Giassas, MD
Sotiria" General Hospital, 1st, 3rd, 8th Dep of Pulmonary Diseases	Recruiting
Athens, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +30281392857 secretary@horg.gr
Principal Investigator: Athina Aggelidou, MD
Principal Investigator: Ourania Anagnostopoulou, MD
Principal Investigator: A. Xristou, MD
"Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology	Recruiting
Piraeus, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Nikos Ziras, MD
401 Military Hospital, Medical Oncology Unit	Recruiting
Athens, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Charalambos Christophillakis, MD
"Theagenion" Anticancer Hospital of Thessaloniki	Recruiting
Thessaloniki, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Ioannis Mpoukobinas, MD
Air Forces Military Hospital, Dep of Medical Oncology	Recruiting
Athens, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@med.uoc.gr
Contact: Spyros Georgiadis +302106457968 secretary@med.uoc.g
Principal Investigator: Nikos Kentepozidis, MD
"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Recruiting
Athens, Greece
Contact: Nikoleta Karkatzou, MD +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Aris Polyzos, MD

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 ( John Souglakos )
Study ID Numbers:	CT/07.23
Study First Received:	June 25, 2008
Last Updated:	January 29, 2009
ClinicalTrials.gov Identifier:	NCT00705549 History of Changes
Health Authority:	Greece: National Organization of Medicines

Keywords provided by Hellenic Oncology Research Group:

Advanced
NSCLC
ERCC1
RRM1

BCRA1
Alimta
Gemcitabine

Study placed in the following topic categories:

Antimetabolites
Thoracic Neoplasms
Immunologic Factors
Immunosuppressive Agents
Antiviral Agents
Carcinoma
Docetaxel
Pemetrexed
Vinorelbine
Radiation-Sensitizing Agents

Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Lung Diseases
Non-small Cell Lung Cancer
Gemcitabine
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Docetaxel
Neoplasms by Site
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Therapeutic Uses
Gemcitabine

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Enzyme Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Vinorelbine
Radiation-Sensitizing Agents
Lung Diseases
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 06, 2009