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Protocol Details

A Phase I/II Trial of TRC102 (methoxyamine HCl) in Combination with Temozolomide in Patients with Relapsed Solid Tumors and Lymphomas

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

13-C-0118

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 120

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Solid Tumors;
Lymphomas;
DNA Damage;
Pharmacodynamics;
Pharmacokinetics

Recruitment Keyword(s)

None

Condition(s)

Lymphomas;
Solid Tumors;
NSCLC;
Metastatic Colon Carcinoma;
Granulosa Cell Ovarian Cancer

Investigational Drug(s)

TRC102

Investigational Device(s)

None

Intervention(s)

Drug: TRC 102

Supporting Site

National Cancer Institute

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.

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Eligibility

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 100,000/mcL

Total bilirubin less than or equal to1.5 X institutional ULN

AST(SGOT)/ALT(SGPT) less than 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 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: patient must not have been diagnosed with another cancer within the last 3 years.

-Phase II only: patients with colorectal cancer with known MSI-high disease who have previously been treated 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.

Eligibility Criteria (Healthy volunteer blood donors)

-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.


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Citations:

Liu L, Nakatsuru Y, Gerson SL. Base excision repair as a therapeutic target in colon cancer. Clin Cancer Res. 2002 Sep;8(9):2985-91.

Yan L, Bulgar A, Miao Y, Mahajan V, Donze JR, Gerson SL, Liu L. Combined treatment with temozolomide and methoxyamine: blocking apurininc/pyrimidinic site repair coupled with targeting topoisomerase IIalpha. Clin Cancer Res. 2007 Mar 1;13(5):1532-9.

Kinders RJ, Hollingshead M, Lawrence S, Ji J, Tabb B, Bonner WM, Pommier Y, Rubinstein L, Evrard YA, Parchment RE, Tomaszewski J, Doroshow JH; National Cancer Institute Phase 0 Clinical Trials Team. Development of a validated immunofluorescence assay for >=H2AX as a pharmacodynamic marker of topoisomerase I inhibitor activity. Clin Cancer Res. 2010 Nov 15;16(22):5447-57. doi: 10.1158/1078-0432.CCR-09-3076. Epub 2010 Oct 5.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Alice P. Chen, M.D.
National Cancer Institute (NCI)
BG 31 RM 3A44
31 CENTER DR
BETHESDA MD 20814
(301) 496-4291
chenali@mail.nih.gov

Jennifer H. Zlott
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 12N226
10 Center Drive
Bethesda, Maryland 20892
(301) 435-5664
zlottjh@mail.nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT01851369

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