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

Primary Purpose

Small Cell Lung Cancer Recurrent

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Temozolomide
Sponsored by
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Small Cell Lung Cancer Recurrent

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed SCLC with MGMT methylation.
  • Patient previously treated by one or two chemotherapy lines.
  • Age ≤ 75 and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
  • Patients must have measurable disease, defined as at least one lesion than can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20mm with conventional techniques or as >10mm with spiral CT scan.
  • Patient with controlled brain metastases are eligible.
  • Patient previously treated with chest and/or brain RT are eligible.
  • Life expectancy >3 months.
  • Patient must have normal organ and marrow function as defined below: leukocytes >3,000/μL, absolute neutrophil count >1,000/μL, platelets>100,000/μL, total bilirubin within normal institutional limits, AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal, creatinine within normal institutional limits
  • Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Histologically or cytologically confirmed SCLC without MGMT methylation.
  • Patients who have received three or more previous chemotherapy lines for small cell lung cancer or radiotherapy on target lesions.
  • Symptomatic uncontrolled CNS metastasis.
  • Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  • Presence of infection.
  • History or evidence of malabsorption syndrome or disease that may significantly affect gastrointestinal function.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or other agents used in the study.
  • Presence of medical problems of sufficient severity to prevent full compliance with the study.
  • Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix).

Sites / Locations

  • Ircc Irst
  • Oncologia Medica, Azienda ospedaliera universitaria di Ferrara
  • Oncologia Medica AOU Policlinico di Modena
  • U.O. Oncologia Medica
  • U.O Oncologia medica
  • UO Oncologia Medica, Ospedale S.Maria delle Croci
  • U.O Oncologia medica
  • Oncologia Medica Ospedale Guglielmo da Saliceto

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide

Arm Description

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

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR):
The percentage of patients whose cancer achieve either a partial response or a complete response

Secondary Outcome Measures

Time to tumor progression (TTP)
It is defined as the time from registration until objective tumor progression NOT including death. Patients died for any cause or who are lost at follow up are censored.
Overall survival time (OS):
Time from enrolment to the date of death. For subjects with no known date of death, survival time will be censored at the date of their last on-study assessment.

Full Information

First Posted
June 16, 2015
Last Updated
November 8, 2018
Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
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1. Study Identification

Unique Protocol Identification Number
NCT02477813
Brief Title
Temozolomide in Patients Affected by Relapsed Sensitive or Refractory Small Cell Lung Cancer With MGMT Methylation
Acronym
TeRes
Official Title
Phase II Trial of Temozolomide in Patients Affected by Relapsed Sensitive or Refractory Small Cell Lung Cancer With MGMT Methylation (TeRes). GOPAV03
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Terminated
Why Stopped
Lack of eligible patient recruitment
Study Start Date
January 2015 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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 .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer Recurrent

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
200 mg/m2 die for 5 consecutive days every 28 days. Treatment will be continued until tumor progression, intolerable toxicity or patient refusal
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR):
Description
The percentage of patients whose cancer achieve either a partial response or a complete response
Time Frame
from randomization up to 3 years
Secondary Outcome Measure Information:
Title
Time to tumor progression (TTP)
Description
It is defined as the time from registration until objective tumor progression NOT including death. Patients died for any cause or who are lost at follow up are censored.
Time Frame
from randomization up to 36 months
Title
Overall survival time (OS):
Description
Time from enrolment to the date of death. For subjects with no known date of death, survival time will be censored at the date of their last on-study assessment.
Time Frame
from randomization up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed SCLC with MGMT methylation. Patient previously treated by one or two chemotherapy lines. Age ≤ 75 and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2. Patients must have measurable disease, defined as at least one lesion than can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20mm with conventional techniques or as >10mm with spiral CT scan. Patient with controlled brain metastases are eligible. Patient previously treated with chest and/or brain RT are eligible. Life expectancy >3 months. Patient must have normal organ and marrow function as defined below: leukocytes >3,000/μL, absolute neutrophil count >1,000/μL, platelets>100,000/μL, total bilirubin within normal institutional limits, AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal, creatinine within normal institutional limits Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Histologically or cytologically confirmed SCLC without MGMT methylation. Patients who have received three or more previous chemotherapy lines for small cell lung cancer or radiotherapy on target lesions. Symptomatic uncontrolled CNS metastasis. Participation in another clinical trial with any investigational agents within 30 days prior to study screening. Presence of infection. History or evidence of malabsorption syndrome or disease that may significantly affect gastrointestinal function. History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or other agents used in the study. Presence of medical problems of sufficient severity to prevent full compliance with the study. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Casanova, MD
Organizational Affiliation
Oncology Department, PO Ravenna, AUSL della Romagna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ircc Irst
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Oncologia Medica, Azienda ospedaliera universitaria di Ferrara
City
Ferrara
State/Province
FE
ZIP/Postal Code
44124
Country
Italy
Facility Name
Oncologia Medica AOU Policlinico di Modena
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
Facility Name
U.O. Oncologia Medica
City
Faenza
State/Province
RA
ZIP/Postal Code
48018
Country
Italy
Facility Name
U.O Oncologia medica
City
Lugo
State/Province
RA
ZIP/Postal Code
48022
Country
Italy
Facility Name
UO Oncologia Medica, Ospedale S.Maria delle Croci
City
Ravenna
State/Province
RA
ZIP/Postal Code
48121
Country
Italy
Facility Name
U.O Oncologia medica
City
Rimini
State/Province
RN
ZIP/Postal Code
47923
Country
Italy
Facility Name
Oncologia Medica Ospedale Guglielmo da Saliceto
City
Piacenza
ZIP/Postal Code
29121
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

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

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