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 20, 2022
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Tracking Information | |||||||||
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First Submitted Date ICMJE | May 8, 2013 | ||||||||
First Posted Date ICMJE | May 10, 2013 | ||||||||
Last Update Posted Date | May 20, 2022 | ||||||||
Actual Study Start Date ICMJE | July 12, 2013 | ||||||||
Estimated Primary Completion Date | February 1, 2023 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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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Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas | ||||||||
Official Title ICMJE | A Phase I/II Trial of TRC102 (Methoxyamine HCl) in Combination With Temozolomide in Patients With Relapsed Solid Tumors and Lymphomas | ||||||||
Brief 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:
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Detailed Description | Background: -Base excision repair (BER) of DNA repair pathway has been implicated in resistance to both alkylating and antimetabolite chemotherapy. -TRC102 (methoxyamine HCl) acts through a novel mechanism to inhibit BER and has demonstrated the ability to potentiate the activity of the alkylating agent temozolomide (TMZ), in vitro and in vivo. We hypothesize that TRC102 can be safely co-administered with TMZ and would potentiate DNA damage caused by TMZ, resulting in antitumor responses. -Based on responses measured during the Phase I portion of the trial, we will further explore the efficacy of this combination in patients with metastatic colon carcinoma, nonsmall cell lung cancer (NSCLC), and granulosa cell ovarian cancer Primary Objective: -To establish the safety, tolerability, and maximum tolerated dose (MTD) of oral TRC102 in combination with oral TMZ in patients with refractory solid tumors -Evaluate the pharmacokinetic (PK) profile of oral TRC102 when administered in combination with TMZ. -To explore the response rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer Secondary Objective:
cancer, NSCLC, and granulosa cell ovarian cancer Exploratory Objectives:
Eligibility: -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 adenocarcinoma of the colon 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
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. Study Design: Phase I
further evaluate that dose for PK and PD endpoints for evidence of DNA damage and apoptosis. -During the escalation phase, tumor biopsies will be optional. During the expansion phase, (once MTD is reached), mandatory paired tumor biopsies will be pursued in the 15 additional patients enrolled to further evaluate PD endpoints. Phase II -This is a 3-arm Simon 2-stage design trial evaluating independently the response rate of patients with colon, NSCLC, and granulosa cell ovarian cancer.
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: TRC 102
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.
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Study Arms ICMJE | Experimental: 1
combination treatment with oral TRC102 and oral TMZ for days 1-5 of 28-day cycles
Intervention: Drug: TRC 102
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
140 | ||||||||
Original Estimated Enrollment ICMJE |
40 | ||||||||
Estimated Study Completion Date ICMJE | February 1, 2023 | ||||||||
Estimated Primary Completion Date | February 1, 2023 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
excluded from this study.
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.
Exclusion Criteria (Patients)
(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.
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
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Administrative Information | |||||||||
NCT Number ICMJE | NCT01851369 | ||||||||
Other Study ID Numbers ICMJE | 130118 13-C-0118 |
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Has Data Monitoring Committee | Not Provided | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||||
Responsible Party | National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) | ||||||||
Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | ||||||||
Verification Date | December 8, 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |