A Phase 2 study of temozolomide (SCH 52365) in Subjects with Advanced Aerodigestive Tract Cancers Selected for Methylation of O6-Methyl-guanine-DNA Methyltransferase (MGMT) Promoter

Phase 1

• Conditions: Advanced Aerodigestive Tract Cancers (Colorectal Cancer (CRC), Non Small Cell Lung Cancer (NSCLC), Head and Neck (H&N), Esophageal Cancer; MedDRA version: 8.1 Level: LLT Classification code 10028980 Term: Neoplasm

• Registration Number: EUCTR2006-003169-15-GB
• Lead Sponsor: Schering Plough Research Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-01-08
• Study Completion: 2009-06-11
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 160

Inclusion Criteria

M1. Subject must have one of the following histologically or cytologically confirmed tumor types: a. CRC: metastatic disease. b. NSCLC: locally advanced, inoperable, or metastatic disease. Eligible histologies include (but are not restricted to) squamous cell, adenocarcinoma, adenosquamous carcinoma, and large cell carcinoma. c. H & N cancer: recurrent or metastatic disease, including squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx. d. Esophageal cancer: recurrent or metastatic disease, including (but not restricted to) squamous cell carcinoma and adenocarcioma and also including cancers at the gastroesophageal junction.
2. Subjects must have a tumor sample, when available from initial diagnosis or later, and a serum sample taken during the screening period. The available tumor samples can be from biopsy or surgical resection of primary or metastatic lesions. If a subject has no prior surgical resection or biopsy of the tumor, or the available tumor sample is insufficient for screening, and a new biopsy for screening is not clinically indicated, the subject may be screened based on the serum sample alone.
3. Subjects must demonstrate methylated MGMT promoter in the most recent tumor tissure sample or in the serum sample.
4. Subjects must have relapsed or recurrent disease with no other potentially curative treatment option available in the opinion of the investigator.
5. Subjects must meet the requirement listed below regarding their prior chemotherapy, biological therapy, immunotherapy, or targeted therapy for advanced/metastatic disease. In addition to the prior therapy limits below, subjects may also have received adjuvant or neoadjuvant therapy. a. CRC: no more than 3 prior regimens. b. NSCLC: no more than 3 prior regimens. c. H & N cancer: no more than 2 prior regimens. d. Esophageal cancer: no more than 2 prior regimens.
6. Subjects must have resolution of all clinically significant toxic effects (excluding alopecia, acne, skin rash) of any prior surgery, radiotherapy, immunotherapy, targeted therapy or chemotherapy to Grade 7. Subjects must have at least one measureable lesion, as defined by Response Evaluation Criteria in Solid Tumors (RESIST). If the subject has received radiation therapy, this measurable lesion must be outside the area of prior radiation or has demonstrated clear progression following completion of radiation therapy.
8. Subjects must have an Eastern Coorperative Oncology group (ECOG) performance status of 0, 1 or 2.
9. Subjects must have adequate hematologic, renal, and liver function, as demonstrated by laboratory values performed within 14 days, inclusive, prior to administration of study drug: a. Absolute neutrophil count >/= 1, 500/mm3 b. Platelet count >/=100,000/mm3 c. Hemoglobin >/=9g/dl d. Blood urea nitrogen (BUN)/urea and serum creatinine 10. S

Exclusion Criteria

Subjects will be excluded from entry if any of the criteria are met:
1. Subjects who have received treatment for a second malignancy within 1 year before screening, and are considered to be at risk of relapse within 1 year after screening.
2. Subjects with unstable or progressing CNS metastasis. Subjects with known CNS metastasis may be included if a) the subject is asymptomatic, b)there is no requirement for steroids or antiseizure medications, or the required doses are stable, and c) there is no associated midline shift or (in the opinion of the investigator) significant edema.
3. Subjects with clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease that would make implementation of the protocol difficult.
4. Subjects who received prior temozolomide or dacarbazine treatment.
5. Women who are breast-feeding, pregnant, or intend to become pregnant.
6. Subjects with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
7. Subjects who have used any investigational drugs within 30 days of start of study treatment 8. Subjects who are participating in any other therapeutic clinical study. Subjects who are in the follow-up phase and have been at least 30 days off the study treatments in other studies may be allowed.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine response rate (complete and partial response) for temozolomide when administered on Days 1 to 7 and Days 15-21 of each 28 day cycle in subjects with methylated MGMT protomoter.;Secondary Objective: To evaluate the safety of temozolomide and estimate response duration, time to disease progression, and overall survival.;Primary end point(s): Response Rate (complete and partial).