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Study to Test the Safety of an Experimental Drug, LMP744, in Patients with Relapsed Solid Tumors or Lymphomas

Trial Status: Active

This phase I trial studies the side effects and best dose of topoisomerase-1 Inhibitor LMP744 in treating patients with solid tumors that have come back after a period of improvement (relapsed) or lymphomas that have progressed after all previous therapy or have no standard of care therapy. Topoisomerase-1 Inhibitor LMP744 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • 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
  • Patients must have measurable or evaluable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 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]) =< 2.5 x institutional upper limit of normal (ULN)
  • Serum creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with serum creatinine levels > 1.5 x higher than institutional normal
  • Anticoagulation with low-molecular-weight heparin (LMWH) or any direct oral anticoagulant (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
  • 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 >= 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 principal investigator's (PI’s) discretion, and should have recovered to grade 1 or baseline from any toxicities
  • Patients receiving denosumab or bisphosphonates for any cancer, or undergoing androgen deprivation therapy for prostate cancer, are eligible for this therapy
  • Prior therapy with topoisomerase I inhibitors is allowed
  • Human immunodeficiency virus (HIV)-positive patients are eligible provided the following criteria are met: CD4 count > 350/mm^3, an undetectable viral load, and not receiving prophylaxis antibiotics
  • 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
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to provide blood and new tumor biopsy samples for research purposes if on the expansion phase of the study

Exclusion Criteria

  • Patients who are receiving any other investigational agents
  • 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
  • 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 >= 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
  • 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

Maryland

Bethesda
National Cancer Institute Developmental Therapeutics Clinic
Status: ACTIVE
Contact: Geraldine O'Sullivan Coyne
Phone: 800-411-1222
National Institutes of Health Clinical Center
Status: ACTIVE
Contact: Geraldine O'Sullivan Coyne
Phone: 800-411-1222

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE
Contact: James Jinhak Lee
Phone: 412-647-8073

PRIMARY OBJECTIVE:

I. To establish the safety, tolerability and the maximum tolerated dose (MTD) of topoisomerase-1 Inhibitor LMP744 (LMP744 [NSC 706744]) administered intravenously (IV) daily for 5 days (once daily [QD] x 5) schedule in patients with refractory solid tumors and lymphomas.

SECONDARY OBJECTIVE:

I. Characterize the pharmacokinetic (PK) profile of LMP744.

EXPLORATORY OBJECTIVES:

I. Evaluate the effect of LMP744 on markers of deoxyribonucleic acid (DNA) damage (gamma H2AX, pNbs1, pATR, ERCC1, RAD51) and epithelial-mesenchymal transition (EMT) in circulating tumor cells (CTCs) and pre- and post- treatment tumor biopsies in patients at the expansion cohort.

II. To assess preliminary anti-tumor activity of LMP744.

OUTLINE: This is a dose-escalation study.

Patients receive topoisomerase-1 Inhibitor LMP744 IV over 1 hour on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
Geraldine O'Sullivan Coyne

  • Primary ID 10002
  • Secondary IDs NCI-2016-00787, 17-C-0045, 162675, P10002
  • Clinicaltrials.gov ID NCT03030417