Overview
TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas
Status:
Recruiting
Recruiting
Trial end date:
2022-02-01
2022-02-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
Background: - TRC102 is a new cancer treatment drug that may help improve the results of chemotherapy. It blocks tumor cells' attempts to repair damaged DNA, which may allow chemotherapy to kill the cells more easily. Researchers want to see how well it works with temozolomide, a chemotherapy drug that is designed to damage tumor cell DNA. These drugs will be given to people who have advanced solid tumors or lymphomas that have not responded to earlier treatments. Objectives: - To test the safety and effectiveness of TRC102 and temozolomide for advanced solid tumors and lymphomas. Eligibility: - Individuals at least 18 years of age who have advanced solid tumors or lymphomas that have not responded to earlier treatments. Design: - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies. - Participants will take TRC102 and temozolomide for 28-day cycles of treatment. They will take temozolomide and TRC 102 by mouth once a day on days 1-5. Participants will keep a diary to record doses and any side effects. - Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will also be collected. - Participants will continue their treatment as long as the cancer does not grow and there are no severe side effects.Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
National Cancer Institute (NCI)Treatments:
TemozolomideCriteria
- 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.