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
- Conditions
- Advanced Aerodigestive Tract Cancers (Colorectal Cancer (CRC), Non Small Cell Lung Cancer (NSCLC), Head & Neck (H & N), Esophageal Cancer)MedDRA version: 8.1 Level: LLT Classification code 10028980 Term: Neoplasm
- Registration Number
- EUCTR2006-003169-15-GR
- Lead Sponsor
- Schering-Plough Research Institute
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 160
1. Subjects 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: metastaatic disease, including squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx.
d. Esophageal cancer: metastatic disease, including (but not restricted to) squamous cell carcinoma and adenocarcinoma, and also including cancers at the gastroesophageal junction.
2. Subjects must have a tumor sample available from initial diagnosis or later and a serum/plasma sample taken during the screening period. The available tumor samples can be from the biopsy or surgical resection of primary or metastatic lesions.
3. Subjects must demonstrate methylated MGMT promoter in the most recent tumor tissue sample or in the serum/plasma sample.
4. Subjects must have relapsed or recuurent disease with no other potentially curative treatment option available in the opinion of the investigator.
5. Subjects must meet the requirements listed below regarding their prior chemotherapy, biological therapy, immunotherapy, or targeted therapy for metastatic disease. In addition to the prior therapy limits below, subjects may also have received adjuvant ot neoadjuvant therapy.
a. CRC: no more than 3 prior regimens.
b. NSCLC: no more than 2 prior regimens.
c. H & N cancer: no more than 1 prior regimen.
d. Esophageal cancer: no more than 1 prior regimen.
6. Subjects must have resolution of all clinically significant toxic effects (excluding alopecia, acne, skin rash) of any prior surgery, radiotherapy, biological therapy, 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.
8. Subjects must have an Eastern Cooperative 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 coount >/= 100,000/mm3
c. Hemoglobin >/= 9 g/dl
d. Blood urea nitrogen(BUN)/urea and serum creatinine e. Total serum bilirubin f. Alkaline phosphatase of </= 2 x ULN, or in the presence of documented liver or bone metastases, alkaline phosphatase </= 5 x
1. Subjects who have had any other type of cancer within 5 years of study start, with the exception of surgically cured carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
2. Subjects with known (past or present) brain or leptomeningeal metastasis.
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 dicarbazine treatment.
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 orally on Days 1 to 7 and Days 15 to 21 of each 28-day cycle in subjects with methylated MGMT promoter.;Primary end point(s): Response rate (complete and partial).;<br> Secondary Objective: To evaluate the safety of temozolomide and estimate response duration, time to disease progression, and overall survival.<br> Exploratory Objectives:<br> To explore the correlation of O6-methyl-guanine-DNA methyltransferase (MGMT) status in tumor tissue samples and in serum/plasma samples.<br> To assess the impact of mismatch repair (MMR) status on response.<br>
- Secondary Outcome Measures
Name Time Method