Temozolomide in Patients Affected by Relapsed Sensitive or Refractory Small Cell Lung Cancer With MGMT Methylation — TeRes  

Small Cell Lung Cancer Recurrent Clinical Trial

Official title: Phase II Trial of Temozolomide in Patients Affected by Relapsed Sensitive or Refractory Small Cell Lung Cancer With MGMT Methylation (TeRes). GOPAV03

Status Terminated

Clinical Trial Summary

It is a single-arm, open label clinical trial. Patients affected by relapsed or refractory small-cell lung cancer patients with MGMT promoter methylation are included in this study; they will be treated with oral Temozolomide 200 mg/m2 die for 5 consecutive days every 28 days. Treatment will be continued until tumor progression, intolerable toxicity or patient refusal.

A Minimax Simon 2-stage design will be used. - First stage: 9 patients If 1 or less responses will be observed, the trial will be ended.- Second stage: other 10 patients (for a total of 19 subjects enrolled) If 5 or less responses will be observed in 19 patients, the treatment will not be considered active, while if 6 or more responses will be observed, the treatment will be considered sufficiently active to warrant further testing. Since the rate of methylation ranges from 20 to 48% the number of patients to be screened should be between 40 and 95.

The primary objective is to determine the overall response rate [ORR = CR + PR]; the secondary objectives are to determine the time to Progression (TTP), the overall Survival (OS), the toxicity and the correlation between response Rate (RR) and the level of MGMT promoter methylation and/or base excision repair (BER) genes alterations.

Clinical Trial Description

This is a single-arm, open-label, phase II study. Patients must have histologically or cytologically confirmed small cell lung cancer (SCLC), both limited or extensive disease, relapsed after one or two prior chemotherapy regimens MGMT promoter methylation status will be evaluated on a histological tissue sample (after patient signature of a specific informed consent form for this biological evaluation) using Pyrosequencing technique and the main 10 CpG islands of MGMT promoter will be studied. Only patients with MGMT promoter methylation will be enrolled in the clinical trial. To be eligible patients may have received 1 or 2 prior chemotherapeutic regimens. Patients with brain metastases may be enrolled.

Patients will be informed about the palliative nature of the treatment . Patients will be treated with oral Temozolomide 200 mg/m2/die for 5 consecutive days .

Treatment will be repeated every 28 days and continued until disease progression, intolerable toxicity or patient refusal.

Response to chemotherapy will be monitored every three cycles by CT scan of the chest and the abdomen and computed tomography scan or magnetic resonance imaging of the whole brain. Response to treatment will be evaluated according to RECIST 1.1 criteria.

In case of progressive disease (PD) the patients will discontinue treatment. In case of stable disease (SD), partial response (PR) or complete response (CR) patients continue treatment until disease progression, intolerable toxicity or patient refusal.

After the end of treatment, if disease progression will not occur, patients will be evaluated every 3 months by CT scan of the chest and the abdomen and CT scan or RM of the whole brain until disease progression.

Planned follow-up visits will continue until disease progression and patients will be monitored for survival and toxicity . ;

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer Recurrent
• Small Cell Lung Carcinoma

• NCT number: NCT02477813
• Study type: Interventional
• Source: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Status: Terminated
• Phase: Phase 2
• Start date: January 2015
• Completion date: June 2018