A phase 2 study of temozolomide in patients affected by metastatic colonrectal cancer with hypermethylation of 06-methylguanine-dna-methyltransferase

• Conditions: metastatic colonrectal cancer; MedDRA version: 15.0Level: HLTClassification code 10010023Term: Colorectal neoplasms malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2012-002766-13-IT
• Lead Sponsor: POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09-03
• Last Update Posted: 10 February 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

-Pathologically confirmed colorectal adenocarcinoma and documented metastatic disease
-MGMT promoter hypermethylation assessed by MS-PCR. The analysis will be performed at Università Cattolica del Sacro Cuore, Molecular Pathology Lab.
-Disease progression during or following at least two lines of chemotherapy including fluoropyrimidines, irinotecan, oxaliplatin, anti-VEGF and (if KRAS wild-type) anti EGFR drugs, or unacceptable toxicity to these drugs.
-Progression free interval less than 6 months from the end of the previous treatment
-Male and female patients, age = 18 years
-Performance Status (ECOG): = 2
-At least one measurable lesion meeting the RECIST 1.1 criteria
-Written and signed informed consent obtained prior to beginning any protocol-specific procedures.
-Life expectancy =12 weeks
-Effective means of contraception (i.e. sexual abstinence) during the study and for a period of at least 6 mon ths after the last administration of the study drug.
-Adequate hematological function (White Blood Cell count = 3 x 109/l, Absolute neutrophil count = 1.5 x 109/l, and platelet count = 100 x 109/l)
-Adequate liver function (total bilirubin < 1.5 x upper limit of normal, unless the patient has documented Gilbert’s syndrome; ALT = 2.5 x upper limit of normal or = 5 x upper limit of normal in patients with liver metastases)
-Adequate renal function: serum creatinine = 1.5 x upper limit of normal or creatinine clearance = 50 ml/min (according to the formula of Crockcroft and Gault)
-INR and aPTT = 1.5 x upper limit of normal (unless on therapeutic anti-coagulation)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21

Exclusion Criteria

-History of any other serious or uncontrolled disease that contraindicates the use of the investigational drug
-Pregnancy or breast feeding (female patients with childbearing potential must have a negative serum beta-HCG).
-Bowel obstruction
-Alcohol or drug abuse.
-Legal incapacity or limited legal capacity
-Existing acute reversible effects of prior treatment. This generally means at least 3 weeks should have elapsed since prior chemotherapy and at least 4 weeks since prior (radical) radiotherapy or major surgery with full recovery
-History of another malignancy within 5 years prior of enrollment, except for adequately treated carcinoma in situ of the cervix and non-melanoma skin cancer. Patients treated for other malignancies with curative intent and disease free at least for 5 years are elegible.
-Brain metastasis not well controlled. Eligible patients must be asymptomatic, can not be receiving steroids or anticancer treatment, and must be enrolled at least 1 month after the end of the radiotherapy treatment. CT or MRI scan of the brain is mandatory in case of clinical suspicion of CNS metastases.
-Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
-Current known infection with HIV, HBV, or HCV
-Known hypersensitivity to the study drug or to one of the excipients
-Documented intolerance to galactose, lattase deficiency or galactose malabsorption

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: -To assess the activity (in terms of response rate according to RECIST 1.1 criteria) of temozolomide (TMZ) in patients with refractory metastatic colorectal cancer with hypermethylation of MGMT;Secondary Objective: -Disease control rate<br>-Duration of response<br>-Progression free survival<br>-Tolerability and safety<br>-Quality of life;Primary end point(s): -Objective tumor response rate according to RECIST 1.1 criteria<br>-Duration of response, as the time period from first documentation of response (complete or partial response) to the date of first occurrence of documented disease progression<br>-Progression-free survival, defined as the time period from start of the treatment to the date of first occurrence of documented disease progression or death from any cause within 60 days from the last disease assessment or from cycle 1, day 1<br>-Overall survival, defined as the time period from enrollment to death from any cause.;Timepoint(s) of evaluation of this end point: 1 month

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Incidence and grading of adverse events and serious adverse events classified according to NCI-CTCAE 4.0<br>Quality of life assessment:<br>-Quality of life will be assessed by EORTC QLQ C-30 questionnaire;Timepoint(s) of evaluation of this end point: 1 month