TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas

This is an interventional treatment trial for Lymphomas focused on measuring Solid Tumors, Lymphomas, DNA Damage, Pharmacodynamics, Pharmacokinetics Read More

• 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, 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 TRC102 in combination with 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.
• 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

AST(SGOT)/ALT(SGPT) less than or equal to 3 X institutional upper limit of normal; 5.0 x 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 m2 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 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 squamous cell carcinoma from which the patient is currently in complete remission.
  • Any other cancer from which the patient has been disease-free for three years.
  • Adequately managed stage I or II well differentiated thyroid or prostate cancer is also eligible, wherein the patient is not required to be in complete remission.
• Phase II only: patients with colorectal cancer with known MSI-high disease who have not previously been treated with immunotherapy or who have refused treatment with immunotherapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC102 or TMZ.
• Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of possible PK interactions with TRC102.

(Healthy volunteer blood donors)

Please note: healthy adult volunteers will no longer be recruited to provide blood for this study as we will no longer perform the hemolysis analysis.

• Age greater than 18 years; hemoglobin greater than or equal to 12 g/dL; no history of bleeding problems; not taking aspirin or any medication that may affect erythrocyte biochemistry
• Willingness to sign the healthy volunteer informed consent form.