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

NCT ID: NCT00705549

Last Updated: 2013-02-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2011-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Small-Cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Gemzar/Cisplatin

Group Type EXPERIMENTAL

Gemcitabine

Intervention Type DRUG

Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8

Cisplatin

Intervention Type DRUG

Cisplatin I.V at the dose of 75mg/m2 on Day 1

2

Taxotere/Cisplatin

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Cisplatin I.V at the dose of 75mg/m2 on Day 1

Docetaxel

Intervention Type DRUG

Docetaxel I.V at the dose of 75mg/m2 on Day 1

3

Cisplatin/Navelbine metronomic

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Cisplatin I.V at the dose of 80mg/m2 on Day 1

Vinorelbine

Intervention Type DRUG

Vinorelbine per os 50mg every Monday, Wednesday and Friday

4

Taxotere/Gemzar

Group Type EXPERIMENTAL

Gemcitabine

Intervention Type DRUG

Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8

Docetaxel

Intervention Type DRUG

Docetaxel I.V at the dose of 75mg/m2 on Day 1

5

Gemzar

Group Type EXPERIMENTAL

Gemcitabine

Intervention Type DRUG

Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8

6

Taxotere

Group Type EXPERIMENTAL

Docetaxel

Intervention Type DRUG

Docetaxel I.V at the dose of 75mg/m2 on Day 1

7

Navelbine metronomic

Group Type EXPERIMENTAL

Vinorelbine

Intervention Type DRUG

Vinorelbine per os 50mg every Monday, Wednesday and Friday

8

Alimta/Cisplatin

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Cisplatin I.V at the dose of 75mg/m2 on Day 1

Pemetrexate

Intervention Type DRUG

Pemetrexate I.V 500mg/m2 on Day 1

9

Alimta/Gemzar

Group Type EXPERIMENTAL

Gemcitabine

Intervention Type DRUG

Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8

Pemetrexate

Intervention Type DRUG

Pemetrexate I.V 500mg/m2 on Day 1

10

Taxotere

Group Type EXPERIMENTAL

Docetaxel

Intervention Type DRUG

Docetaxel I.V at the dose of 75mg/m2 on Day 1

11

Alimta

Group Type EXPERIMENTAL

Pemetrexate

Intervention Type DRUG

Pemetrexate I.V 500mg/m2 on Day 1

Interventions

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Gemcitabine

Gemcitabine I.V at the dose of 1000mg/m2 on Day 1 and Day 8

Intervention Type DRUG

Cisplatin

Cisplatin I.V at the dose of 75mg/m2 on Day 1

Intervention Type DRUG

Docetaxel

Docetaxel I.V at the dose of 75mg/m2 on Day 1

Intervention Type DRUG

Cisplatin

Cisplatin I.V at the dose of 80mg/m2 on Day 1

Intervention Type DRUG

Vinorelbine

Vinorelbine per os 50mg every Monday, Wednesday and Friday

Intervention Type DRUG

Pemetrexate

Pemetrexate I.V 500mg/m2 on Day 1

Intervention Type DRUG

Other Intervention Names

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Gemzar CDDP Taxotere CDDP Navelbine Alimta

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital of Crete

OTHER

Sponsor Role collaborator

Hellenic Oncology Research Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Souglakos, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Crete, Dep of Medical Oncology

Locations

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University General Hospital of Alexandroupolis, Dept. of Medical Oncology

Alexandroupoli, , Greece

Site Status

"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine

Athens, , Greece

Site Status

401 Military Hospital, Medical Oncology Unit

Athens, , Greece

Site Status

Air Forces Military Hospital, Dep of Medical Oncology

Athens, , Greece

Site Status

IASO" General Hospital of Athens, 1st Dep of Medical Oncology

Athens, , Greece

Site Status

Sismanogleio General Hospital, 1st, 2nd Dep of Pulmonary Diseases

Athens, , Greece

Site Status

Sotiria" General Hospital, 1st, 3rd, 8th Dep of Pulmonary Diseases

Athens, , Greece

Site Status

"Metaxa's" Anticancer Hospital of Piraeus,1st Dep of Medical Oncology

Piraeus, , Greece

Site Status

"Theagenion" Anticancer Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Countries

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Greece

Other Identifiers

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CT/07.23

Identifier Type: -

Identifier Source: org_study_id

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