| Inclusion Criteria: | 1) Subjects must be 18 years of age or older, of either sex, and of any race.
2) Must have one of the following histologically or cytologically confirmed tumor types: CRC: metastatic disease. NSCLC: locally advanced, inoperable, or metastatic disease. Eligible histologies include squamous cell, adenocarcinoma, adenosquamous carcinoma, & large cell carcinoma. H&N cancer: recurrent or metastatic disease, including squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Esophageal cancer: recurrent or metastatic disease, including but not restricted to squamous cell carcinoma & adenocarcinoma, & also including cancers at the gastroesophageal junction.
3) 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.
4) Subjects must demonstrate methylated MGMT promoter in the most recent tumor tissue sample or in the serum sample.
5) Subjects must have relapsed or recurrent disease with no other potentially curative treatment option available in the opinion of the investigator.
6) 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 regimen. d. Esophageal cancer: no more than 2 prior regimen.
7) 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 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.
8) Subjects must have at least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST). 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.
9) Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
10) Subjects must have adequate hematologic, renal, and liver function demonstrated by laboratory values performed within 14 days, prior to administration of study drug: a. Absolute neutrophil count =/> 1,500/mm^3 b. Platelet count =/> 100,000/mm^3 c. Hemoglobin =/> 9 g/dL d. BUN/urea and serum creatinine =/< 1.5 times 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.
11) Subjects must be willing to give written informed consent and able to adhere to dose and visit schedules.
12) Subjects must have a life expectancy of greater than 12 weeks.
13) Subjects must be able to take the study medication capsules orally, or through a feeding tube without the capsules being opened.
14) Women of childbearing potential and men and their female partners of childbearing potential who are currently sexually active must agree to use a medically accepted method of contraception while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).
15) Women of childbearing potential and men and their female partners of childbearing potential who are not currently sexually active must agree to use a medically accepted method of contraception while receiving protocol-specified medication, and for 6 months after stopping the medication should they become sexually active while participating in the study. |