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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

Phase 2
18 Years
Not Enrolling
Non-Small-Cell Lung Cancer

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Trial Information

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

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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Objective responses confirmed by CT or MRI

Safety Issue:


Principal Investigator

John Souglakos, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital of Crete, Dep of Medical Oncology


Greece: National Organization of Medicines

Study ID:




Start Date:

February 2008

Completion Date:

September 2011

Related Keywords:

  • Non-Small-Cell Lung Cancer
  • Advanced
  • ERCC1
  • RRM1
  • BCRA1
  • Alimta
  • Gemcitabine
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms