TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01851369|
Recruitment Status : Recruiting
First Posted : May 10, 2013
Last Update Posted : September 3, 2018
- 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: TRC 102||Phase 1 Phase 2|
Hide Detailed Description
-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
-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
-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
- To explore the progression free survival rate of this combination in patients with colon
cancer, NSCLC, and granulosa cell ovarian cancer
- Investigate tumor genomic and transcriptomic alterations potentially associated with sensitivity and/or the development of resistance to TRC102 and temozolomide.
- Determine the effects of the study treatment on the level of histone gamma-H2AX in circulating tumor cells (CTCs) and tumor and correlate the gamma-H2AX response in tumor and CTCs
- Determine the effects of the study treatment on the levels of cleaved caspase 3, epithelial- mesenchymal transition, and APE in tumor and CTCs
- Determine and characterize the effects of study treatment on erythrocytes
- Characterize the clinical presentation of hemolysis observed in earlier study subjects and explore the possible mechanisms
-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
- No major surgery, radiation, or chemotherapy within 4 weeks prior to entering the study
- Adequate organ function
- Healthy adult volunteers greater than or equal to 18 years of age will be consented to donate research blood
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
- This is an open-label Phase I trial; traditional 3+3 design.
- Oral TRC102 and oral TMZ will be administered daily, days 1-5 in 28-day cycles
- Once the MTD is established, up to 15 additional patients will be enrolled at the MTD to
further evaluate that dose for PK and PD endpoints for evidence of DNA damage and
-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.
-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.
- Patients with a body surface area (BSA) of greater than or equal to 1.6 m(2) will receive 125 mg of TRC 102 and 150 mg/m2 of TMZ PO qday x 5 every 28 days (DL6). Patients with a BSA of <1.6 m(2) will receive 100 mg of TRC 102 and 150 mg/m2 of TMZ PO qday x 5 every 28 days (DL5).. Each cycle will be 28 days.
- The accrual ceiling for the Phase II portion is 75 patients.
- Mandatory paired tumor biopsies will be pursued to further evaluate PD endpoints.
|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|
|Study Start Date :||May 8, 2013|
|Estimated Primary Completion Date :||December 24, 2019|
|Estimated Study Completion Date :||February 1, 2020|
combination treatment with oral TRC102 and oral TMZ for days 1-5 of 28-day cycles
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.
- 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 4.0.
- 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).
- Evaluate the pharmacokinetic (PK) profile of oral TRC102 when administered in combination with TMZ [ Time Frame: First 5 days ]
- 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 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, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Alice P Chen, M.D.||National Cancer Institute (NCI)|