TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas
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|ClinicalTrials.gov Identifier: NCT01851369|
Recruitment Status : Recruiting
First Posted : May 10, 2013
Last Update Posted : May 26, 2023
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- 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.
- To test the safety and effectiveness of TRC102 and temozolomide for advanced solid tumors and lymphomas.
- Individuals at least 18 years of age who have advanced solid tumors or lymphomas that have not responded to earlier treatments.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphomas Solid Tumors NSCLC Metastatic Colon Carcinoma Granulosa Cell Ovarian Cancer||Drug: TRC102||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of TRC102 (Methoxyamine HCl) in Combination With Temozolomide in Patients With Relapsed Solid Tumors and Lymphomas|
|Actual Study Start Date :||July 12, 2013|
|Estimated Primary Completion Date :||February 1, 2024|
|Estimated Study Completion Date :||February 1, 2024|
combination treatment with oral TRC102 and oral TMZ for days 1-5 of 28-day cycles
TRC102 has been shown to potentiate the activity of temozolomide by preventing BER and allowing cleavage of TRC102 bound DNA, which will cause DNA strand breaks in cancer cells. We hypothesize that oral TRC102 can be safely co-administered with TMZ and would potentiate DNA damage caused by TMZ resulting in antitumor responses.
- To explore the response rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer [ Time Frame: Response rate one year ]Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
- To establish the safety, tolerability, and maximum tolerated dose (MTD) of oral TRC102 in combination with oral TMZ in patients with refractory solid tumors. [ Time Frame: DLT determined first cycle (28 days) ]Adverse events will be characterized using the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Evaluate the pharmacokinetic (PK) profile of oral TRC102 when administered in combination with TMZ [ Time Frame: First 5 days ]Blood and urine pharmacokinetics will be assessed in the phase I portion of the study.
- To explore the progression free survival rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer [ Time Frame: Duration on study ]To explore the progression free survival rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01851369
|Contact: Jennifer H Zlott||(240) firstname.lastname@example.org|
|Contact: Alice P Chen, M.D.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY dial 711 firstname.lastname@example.org|
|Principal Investigator:||Alice P Chen, M.D.||National Cancer Institute (NCI)|
|Responsible Party:||National Cancer Institute (NCI)|
|Other Study ID Numbers:||
|First Posted:||May 10, 2013 Key Record Dates|
|Last Update Posted:||May 26, 2023|
|Last Verified:||April 27, 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||.All IPD recorded in the medical record will be shared with intramural investigators upon request.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
|Time Frame:||Clinical data available during the study and indefinitely.|
|Access Criteria:||Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI ETCTN Director in conjunction with the NCI/DCTD Regulatory Affairs Branch).|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms by Histologic Type
Immune System Diseases