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Protocol Details

A Phase I Study of Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-C-0045

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Fetuses;
Children

Keywords

Topoisomerase I Inhibitor;
Epithelial-Mesenchymal Transition;
Pharmacodynamics;
DNA Damage;
Pharmacokinetics

Recruitment Keyword(s)

None

Condition(s)

Solid Tumors;
Lymphoma

Investigational Drug(s)

LMP744

Investigational Device(s)

None

Intervention(s)

Drug: LMP744
Other: Ondansetron
Other: Olanzapine
Other: Lorazepam
Other: Diphenoxylate hydrocholoride (HCL) + Atropine Sulfate
Other: Loperamide
Other: Diphenhydramine
Other: Steroid
Other: Epinephrine

Supporting Site

National Cancer Institute

Background:

The new drug LMP744 damages deoxyribonucleic acid (DNA). This causes cell death. Researchers want to see if it can treat certain kinds of cancer. They want to understand how the drug works and how it affects the body.

Objective:

To test the safety of LMP744 and find out the dose of the drug that can be safely given to humans.

Eligibility:

Adults at least 18 years old who have metastatic solid tumors or lymphoma, which have progressed after other treatment.

Design:

Participants will be screened with:

-Vital signs taken

-Blood and urine tests

-Heart tests

-Scans or ultrasound

Some participants will have a tumor sample taken 2 times. A small piece of tumor is removed by a small needle. A scan or ultrasound will guide the process.

The study will be done in 28-day cycles.

Each cycle, participants will get the study drug in a vein for 60 minutes once a day for 5 days.

For day 1 of cycle 1, participants will be admitted to the clinic and have blood and urine taken several times.

At the beginning of each cycle, participants will have a clinic visit and repeat some screening tests. They will also do this twice in the middle of cycle 1 and once in the middle of cycle 2.

After participants stop taking the study drug, they will be followed for 30 days. They may give blood samples. They will be contacted by phone to see how they are doing.

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Eligibility

INCLUSION CRITERIA:

1. Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after initial therapy and without potentially curative options, or patient refuses potentially curative therapy.

2. Patients must have measurable or evaluable disease

3. Age greater than or equal to 18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

5. Life expectancy of greater than 3 months.

6. Patients must have normal organ and marrow function as defined below:

leukocytes greater than or equal to 3,000/mcL

absolute neutrophil count greater than or equal to 1,500/mcL

platelets greater than or equal to 100,000/mcL

total bilirubin within normal institutional limits

Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 (SqrRoot) institutional upper limit of normal (ULN)

Serum creatinine less than or equal to 1.5 (SqrRoot) institutional ULN

OR

creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with serum creatinine levelsgreater than 1.5 x higher than institutional normal.

7. Anticoagulation with low-molecular-weight heparin (LMWH) or any (direct oral anticoagulants (DOAC), e.g., rivaroxaban, apixaban, dabigatran, or edoxaban) will be permitted. Patients receiving treatment with warfarin will be given the option to switch to LMWH or a

DOAC.

8. Patients must have recovered to grade 1 or baseline from adverse events (AEs) and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy, biologic therapy, or definitive radiotherapy within 4 weeks (6 weeks for nitrosoureas and mitomycin C) or 5 half-lives, whichever is shorter, prior to entering the study. Palliative-intent radiotherapy (30 Gy or less) must be completed at least 2 weeks prior to start of treatment, and may not be to a lesion that is included as measurable disease. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) at the PI s discretion, and should have recovered to grade 1 or baseline from any toxicities.

9. Patients receiving denosumab or bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy.

10. Prior therapy with topoisomerase I inhibitors is allowed.

11. Patients with known HIV-positive status are eligible provided the following criteria are met: cluster of differentiation 4 (CD4)11 count >350/mm3, an undetectable viral load, and not receiving prophylaxis antibiotics. Diagnostic HIV testing will not be performed during screening or throughout this study.

12. The effects of LMP744 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. 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. Women and 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 4 months after completion of LMP744 administration.

13. Ability to understand and the willingness to sign a written informed consent document.

14. Willingness to provide blood and new tumor biopsy samples for research purposes if on the expansion phase of the study.

EXCLUSION CRITERIA:

1. Patients who are receiving any other investigational agents.

2. Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to active or uncontrolled infection, immune deficiencies, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or

psychiatric illness/social situations that would limit compliance with study requirements.

3. Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 1 month after treatment of the brain metastases. Patients on anti-seizure medications or steroid therapy may be enrolled at the discretion of the Principal Investigator.

4. Pregnant women are excluded from this study because LMP744 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMP744, breastfeeding should be discontinued if the mother is treated.

INCLUSION OF WOMEN AND MINORITIES:

Both men and women of all races and ethnic groups are eligible for this trial.


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Citations:

Antony S, Kohlhagen G, Agama K, Jayaraman M, Cao S, Durrani FA, Rustum YM, Cushman M, Pommier Y. Cellular topoisomerase I inhibition and antiproliferative activity by MJ-III-65 (NSC 706744), an indenoisoquinoline topoisomerase I poison. Mol Pharmacol. 2005 Feb;67(2):523-30.

Antony S, Agama KK, Miao ZH, Takagi K, Wright MH, Robles AI, Varticovski L, Nagarajan M, Morrell A, Cushman M, Pommier Y. Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance. Cancer Res. 2007 Nov 1;67(21):10397-405. Erratum in: Cancer Res. 2007 Dec 15;67(24):12034.

Meng LH, Liao ZY, Pommier Y. Non-camptothecin DNA topoisomerase I inhibitors in cancer therapy. Curr Top Med Chem. 2003;3(3):305-20.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Alice P. Chen, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CLINICAL CENTER BG RM 8D53
10 CENTER DR
BETHESDA MD 20892
(240) 781-3320
chenali@mail.nih.gov

Murielle Hogu
National Cancer Institute (NCI)

(240) 858-3335
murielle.hogu@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
ncimo_referrals@mail.nih.gov

Clinical Trials Number:

NCT03030417

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