E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Aerodigestive Tract Cancers (Colorectal Cancer (CRC), Non Small Cell Lung Cancer (NSCLC), Head & Neck (H & N), Esophageal Cancer) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028980 |
E.1.2 | Term | Neoplasm |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of temozolomide and estimate response duration, time to disease progression, and overall survival. Exploratory Objectives: To explore the correlation of O6-methyl-guanine-DNA methyltransferase (MGMT) status in tumor tissue samples and in serum/plasma samples. To assess the impact of mismatch repair (MMR) status on response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 </= 1 by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v 3.0 or to within the limits listed in the specific inclusion/exclusion criteria. Subjects must have discontinued prior allowed therapy for at least 4 weeks before start of study treatment. 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 </= 1.5 times upper limit of normal (ULN) e. Total serum bilirubin </= 1.5 x ULN and AST (SGOT)/ALT (SGPT) </= 2 x ULN, or in the presence of documented liver metastases, AST/ALT </= 5 x ULN f. Alkaline phosphatase of </= 2 x ULN, or in the presence of documented liver or bone metastases, alkaline phosphatase </= 5 x ULN.
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E.4 | Principal exclusion criteria |
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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate (complete and partial). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The overall study ends when the last remaining subject has completed or has been discontinued from the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |