TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas

• Eligibility Criteria (Patients)
• Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist.
• Phase II: histologically confirmed colorectal adenocarcinoma post at least two lines of therapy, non-small cell lung cancer (NSCLC) post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy. Patients must have measurable disease.
• Age greater than18 years. Because no dosing or adverse event data are currently available on the use of methoxyamine hydrochloride (TRC102) in combination with Temozolomide (TMZ) in patients less than 18 years of age, children are excluded from this study.
• Patients enrolling in the expansion cohorts must have disease amenable to biopsy and be willing to undergo pre-and post-treatment biopsies.
• Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (Phase I), less than or equal to 1(Phase II).
• Life expectancy of greater than 3 months
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count greater than 1,500/mcL
• Hemoglobin greater than or equal to 10 g/dL without transfusion within 1 week prior to enrollment

Platelets greater than or equal to 100,000/mcL

Total bilirubin less than or equal to1.5 X institutional ULN

Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT)(SGPT) less than or equal to 3 X institutional upper limit of normal; 5.0 x upper limit of normal (ULN) in cases of liver metastases

creatinine less than or equal to 1.5 X institutional ULN

OR

creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels greater than 1.5 mg/dL

-The effects of study drug on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 3 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study drug administration.

• Patients must have completed any chemotherapy, radiation therapy, or biologic therapy greater than or equal to 4 weeks (or 5 half-lives, whichever is shorter) prior to entering the study (6 weeks for nitrosoureas or mitomycin C). Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study and greater than or equal to 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted.
• Patients must be able to swallow whole tablets or capsules; nasogastric or gastric (G)-tube administration is not allowed.
• Ability to understand and the willingness to sign a written informed consent document and to undergo tumor biopsies in the expansion phase.

Exclusion Criteria (Patients)

• Patients who are actively receiving any other investigational agents.
• Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for greater than or equal to 4 weeks without requiring steroid and anti-seizure medications are eligible to participate.
• Phase II only: No other prior malignancies are allowed except for the following:
• Adequately managed stage 0 (carcinoma in situ), I, or II basal cell or squ