Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas

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

Background:

The new drug LMP744 (NSC 706744) 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....

Study Overview

• Status: Completed
• Conditions: Lymphoma; Solid Tumors
• Intervention / Treatment: Drug: LMP744; Other: Ondansetron; Other: Olanzapine; Other: Lorazepam; Other: Diphenoxylate hydrocholoride (HCL) + Atropine Sulfate; Other: Loperamide; Other: Diphenhydramine; Other: Steroid; Other: Epinephrine

Detailed Description

Background:

• Indenoisoquinolines are non-camptothecin inhibitors of topoisomerase 1 (top1) with improved characteristics over their predecessors. Indenoisoquinolines have better chemical stability, producing stable deoxyribonucleic acid (DNA)-top1 cleavage complexes, and exhibit a preference for unique DNA cleavage sites, compared with their camptothecin counterparts.
• They have demonstrated activity against camptothecin-resistant cell lines and produce DNA-protein crosslinks, which are resistant to reversal. They also show less or no resistance to cells overexpressing the ATP-binding cassette (ABC) transporters, ATP-binding cassette super-family G member 2 (ABCG2), and multidrug resistance (MDR-1).

Primary Objectives:

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

Secondary Objectives:

-Characterize the pharmacokinetic (PK) profile of LMP744.

Exploratory Objectives:

• Evaluate the effect of LMP744 on markers of DNA damage phosphorylated H2AX (γH2AX), phosphorylated Nijmegen breakage syndrome 1 (pNbs1), pATR, excision repair cross-complementation group 1 (ERCC1), RAD51 recombinase (RAD51), Topo1cc, topoisomerase 1 (Top1), Schlafen family member 11 (SLFN11) and epithelial-mesenchymal transition (EMT) in circulating tumor cells (CTCs) and pre- and post- treatment tumor biopsies in patients at the expansion cohort.
• Assess preliminary antitumor activity of LMP744.
• Examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance to treatment

Eligibility:

-Adult patients must have histologically documented, relapsed 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.

Study Design:

• Cycle 1 and subsequent cycles: Patients will receive LMP744 administered IV QD over 1 hour on days 1-5 followed by 23 days without drug (28-day cycle).
• Pharmacokinetic (PK) and pharmacodynamic (PD) samples will be collected. Tumor biopsies will be mandatory during the expansion phase.

LMP744 will be administered IV over 1 hour on days 1-5 of each 28-day cycle.

Blood samples for PK analyses will be collected at the following timepoints in cycle 1 only:

Day 1, prior to drug administration, 2 minutes (+/- 2 minutes) before end of infusion, and at appropriate time points post infusion (15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion)

Day 2, 24-hour (hr) post day 1 start of infusion (prior to day 2 infusion), and 2 minutes (+/- 2 minutes) before the end of infusion

Day 3, 24 hr post day 2 start of infusion (prior to day 3 infusion), and 2 minutes (+/- 2 minutes) before end of infusion

Day 4, 24 hr post day 3 start of infusion (prior to day 4 infusion), and 2 minutes (+/- 2 minutes) before end of infusion

Day 5, 24 hr post day 4 start of infusion (prior to day 5 infusion), and 2 minutes (+/- 2 minutes) before end of infusion

Day 8, 72 hr post day 5 start of infusion Blood for circulating tumor cells (CTCs) (optional) will be collected at baseline, on day 3 of

Cycle 1 (within 2 to 4 hours after the start of LMP744 infusion), on day 1 of every subsequent cycle (prior to drug infusion), and at disease progression.

Tumor biopsies (mandatory in expansion phase) will be obtained at baseline and then on day 2 (1-4 hours after the LMP744 infusion) in cycle 1 only.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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 institutional upper limit of normal (ULN)

     Serum creatinine less than or equal to 1.5 institutional ULN

     OR

     creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with serum creatinine levels greater than 1.5 x higher than institutional normal.

  7. Anticoagulation with low-molecular-weight heparin (LMWH) or any direct oral anticoagulant (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 Gray (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 human immunodeficiency virus (HIV)-positive status are eligible provided the following criteria are met: cluster of differentiation 4 (CD4) count >350/mm^3, 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 (NSC 706744) 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Arm - LMP744 (NSC 706744); LMP744 (NSC 706744) will be administered intravenous (IV) over 1 hour on days 1-5 of each 28-day cycle.

Drug: LMP744; Indenoisoquinolines, such as LMP744, are potent inhibitors of the enzyme topoisomerase I (Top1). Top1 is necessary for transcription, replication, recombination, and the repair of double-strand deoxyribonucleic acid (DNA) breaks. It relaxes the supercoiled DNA by introducing a single-strand break, generating a free strand that rotates around the Top1-bound DNA complex. In the absence of external triggers, Top1-DNA cleavage complexes are generally short lived. Top1 inhibitors are potent anticancer agents because they stabilize the formation of the Top1-DNA cleavage complex in tumor cells, which induces DNA damage, delays DNA repair, and results in cell cycle arrest and apoptosis. LMP744 exhibited antitumor activity with lower toxicity than other agents in preclinical studies. Treatment of patients with LMP744 is expected to reduce tumor burden at doses that are well-tolerated.; Other Names: NSC 706744; Other: Ondansetron; Anti-emetic for nausea or vomiting.; Other Names: Zofran; Zofran ODT; Zuplenz; Other: Olanzapine; Persistent nausea or vomiting.; Other Names: Zyprexa; Zyprexa Zydis; Zyprexa Relprevv; Other: Lorazepam; Persistent nausea or vomiting.; Other Names: Ativan; Lorazepam Intensol; Other: Diphenoxylate hydrocholoride (HCL) + Atropine Sulfate; Diphenoxylate hydrocholoride (HCL) 2.5 mg + Atropine Sulfate 0.025 mg/tablet for diarrhea.; Other Names: Lomotil; Lomocot; Lonox; Vi-Atro; Other: Loperamide; Antidiarrheal. 4mg by mouth (PO) after first unformed stool and 2mg PO every 2 hours as long as unformed stools continue. No more than 16mg during a 24-hour period.; Other Names: Diamode; Anti-Diarrheal (loperamide); Imodium A-d; Other: Diphenhydramine; Diphenhydramine 50 mg intravenous (IV) for allergic reaction.; Other Names: Benadryl; Banophen; Nytol; Other: Steroid; For allergic reaction at discretion of principal investigator.; Other: Epinephrine; For allergic reaction at discretion of principal investigator.; Other Names: Adrenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase: Maximum Tolerated Dose (MTD) of LMP744 (NSC 706744)	Maximum tolerated dose (MTD) of LMP744 administered intravenously (IV) daily for 5 days (QD x 5) schedule in participants with refractory solid tumors and lymphomas. The MTD is the dose level at which no more than 1 in 6 participants experience dose-limiting toxicity (DLT), and the dose below that at which ≥ 2 (of ≤ 6) participants have DLT as a result of the drug. A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia.	Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744)	AUC is a measure of the serum concentration of LMP744 over time. It is used to characterize drug absorption.	Day 1, prior to drug administration, 2 minutes before end of infusion; 15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion on Day 1 and prior to start of infusion on Day 2.
Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744)	Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.	Day 1, prior to drug administration, 2 minutes before end of infusion; 15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion on Day 1 and prior to start of infusion on Day 2.
Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744)	Time to maximum (Tmax) concentration of LMP744 (NSC 706744).	Day(D)1, prior to drug administration, 2 minutes (min) before end of infusion; 15 min., 30 min., and 1, 2, 4, and 6 hours (hr) post infusion on D1. 24 hrs post D2, 3, & 4 start of infusion & 2 min. before end of infusion. 72 hrs post D5 start of infusion.
Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744)	To determine the maximum observed plasma concentration of LMP744, blood samples will be collected from participants and analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) or liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method and calculated by non-compartmental analysis.	Day(D)1, prior to drug administration, 2 minutes (min) before end of infusion; 15 min., 30 min., and 1, 2, 4, and 6 hours (hr) post infusion on D1. 24 hrs post D2, 3, & 4 start of infusion & 2 min. before end of infusion. 72 hrs post D5 start of infusion.
Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744)	Percent change in end of infusion drug concentration is a measure of LMP744 (NSC 706744) accumulation in the bloodstream from Day 1 to Day 5.	Day 1 at end of infusion to Day 5 end of infusion.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744)	Antitumor activity is evaluated using the rate of confirmed objective responses according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (i.e., at least a 30% decrease in the sum of the diameters of target lesions compared to the sum of baseline diameters).	Tumor re-staging was performed every 2 cycles for the first year on study then every 3 cycles thereafter until a participant met criteria to be removed from the study; a median of 2 cycles completed and a full range of 0-31 cycles completed.
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining	Levels of pNbs1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)	Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining	Levels of Rad51 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)	Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining	Levels of Top1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)	Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining	Levels of pKap1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)	Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies	Percent of nuclei with ≥19 Top1cc foci in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)	Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining	Levels of γH2AX in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)	Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT)	Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks will be considered dose limiting. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.	Cycle 1 (28 days)
Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level	Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks will be considered dose limiting. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.	Cycle 1 (28 days)
Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	From first drug administration through 30 days after the last dose of study drug is administered, an average of 12.9 months.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Alice P Chen, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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. doi: 10.1124/mol.104.003889. Epub 2004 Nov 5.
• 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. doi: 10.1158/0008-5472.CAN-07-0938. 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. doi: 10.2174/1568026033452546.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2017
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 12, 2023

Study Registration Dates

• First Submitted: January 24, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimated): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): December 10, 2024
• Last Update Submitted That Met QC Criteria: November 16, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; DNA Damage; Topoisomerase I Inhibitor; Epithelial-Mesenchymal Transition
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Sleep Aids, Pharmaceutical; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Dermatologic Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Membrane Transport Modulators; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Respiratory System Agents; Anti-Asthmatic Agents; Neurotransmitter Uptake Inhibitors; Bronchodilator Agents; Anti-Allergic Agents; Adrenergic beta-Agonists; Anticonvulsants; Antipruritics; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antipsychotic Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Sympathomimetics; Vasoconstrictor Agents; Parasympatholytics; Mydriatics; Histamine H1 Antagonists; Olanzapine; Ondansetron; Atropine; Epinephrine; Diphenhydramine; Promethazine; Lorazepam; Loperamide; Antidiarrheals; Diphenoxylate
• Other Study ID Numbers: 170045; 17-C-0045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Requests for all collected individual participant data (IPD) data from clinical trials, conducted under a binding collaborative agreement between National Cancer Institute (NCI)/Division of Cancer Treatment and Diagnosis (DCTD) and a pharmaceutical/biotechnology company, that are not under Data and Safety Monitoring Board (DSMB) monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) Director in conjunction with the NCI/DCTD Regulatory Affairs Branch).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No