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

NCT00705549 | Terminated Phase 2

• 1 other identifier: CT/07.23
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Non-Small-Cell Lung Cancer

Keywords

Advanced; NSCLC; ERCC1; RRM1; BCRA1; Alimta; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) based on the pharmacogenomic profile of the ERCC1, RRM1 and BRCA1 expression

  Objective responses confirmed by CT or MRI

Secondary Outcomes (4)

• Determine the incidence of the different pharmacogenomic profiles as defined by the combined expression of ERCC1, RRM1 and BCRA1

  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 )

• Time to Tumor Progression

  1 year

• Overall Survival

  1 year

• Toxicity

  Toxicity assessment on each chemotherapy cycles

Study Arms (11)

1

EXPERIMENTAL

Gemzar/Cisplatin

Drug: Gemcitabine; Drug: Cisplatin

2

EXPERIMENTAL

Taxotere/Cisplatin

Drug: Cisplatin; Drug: Docetaxel

3

EXPERIMENTAL

Cisplatin/Navelbine metronomic

Drug: Cisplatin; Drug: Vinorelbine

4

EXPERIMENTAL

Taxotere/Gemzar

Drug: Gemcitabine; Drug: Docetaxel

5

EXPERIMENTAL

Gemzar

Drug: Gemcitabine

6

EXPERIMENTAL

Taxotere

Drug: Docetaxel

7

EXPERIMENTAL

Navelbine metronomic

Drug: Vinorelbine

8

EXPERIMENTAL

Alimta/Cisplatin

Drug: Cisplatin; Drug: Pemetrexate

9

EXPERIMENTAL

Alimta/Gemzar

Drug: Gemcitabine; Drug: Pemetrexate

10

EXPERIMENTAL

Taxotere

Drug: Docetaxel

11

EXPERIMENTAL

Alimta

Drug: Pemetrexate

Interventions

Gemcitabine DRUG

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

Also known as: Gemzar

1; 4; 5; 9

Cisplatin DRUG

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

Also known as: CDDP

1; 2; 8

Docetaxel DRUG

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

Also known as: Taxotere

10; 2; 4; 6

Vinorelbine DRUG

Vinorelbine per os 50mg every Monday, Wednesday and Friday

Also known as: Navelbine

3; 7

Pemetrexate DRUG

Pemetrexate I.V 500mg/m2 on Day 1

Also known as: Alimta

11; 8; 9

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hellenic Oncology Research Group: lead
• University Hospital of Crete: collaborator

Study Sites (9)

University General Hospital of Alexandroupolis, Dept. of Medical Oncology

Alexandroupoli, Greece

Location

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

Athens, Greece

Location

401 Military Hospital, Medical Oncology Unit

Athens, Greece

Location

Air Forces Military Hospital, Dep of Medical Oncology

Athens, Greece

Location

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

Athens, Greece

Location

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

Athens, Greece

Location

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

Athens, Greece

Location

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

Piraeus, Greece

Location

"Theagenion" Anticancer Hospital of Thessaloniki

Thessaloniki, Greece

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; Cisplatin; Docetaxel; Vinorelbine; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• John Souglakos, MD

  University Hospital of Crete, Dep of Medical Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2008
• First Posted: June 26, 2008
• Study Start: February 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: February 13, 2013

Record last verified: 2013-02

Locations

GR (9)