Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors

NCT02631733 | Completed Phase 1 FDA Drug

• 4 other identifiers: NCI-2015-0212517-C-00129914ZIABC011078
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given together with liposomal irinotecan in treating patients with solid tumors. Liposomal irinotecan and veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018). Safety and tolerability of escalating doses of liposomal irinotecan and veliparib combination will be evaluated.

  Up to 4 weeks

• Maximum tolerated dose and recommended phase II dose of liposomal irinotecan in combination with veliparib

  Maximum tolerated dose and recommended phase II dose of liposomal irinotecan in combination with veliparib will be determined by incidence of dose limiting toxicities, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018).

  At 28 days

Secondary Outcomes (4)

• Tumor response

  Up to 4 weeks after completion of study treatment

• Objective response rate

  At 24 weeks

• Clinical benefit rate defined as complete response, partial response, or stable disease

  At 24 weeks

• Progression free survival

  Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after completion of study treatment

Other Outcomes (1)

• Biomarker levels

  Up to 4 weeks after completion of study treatment

Study Arms (1)

Treatment (liposomal irinotecan, veliparib)

EXPERIMENTAL

Patients receive liposomal irinotecan IV over 90 minutes on days 1 and 15 and veliparib PO BID on days 5-12 and 19-25 or 3-12 and 17-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within 2-6 days prior to beginning liposomal irinotecan treatment, patients may optionally receive FMX IV and undergo MRI at baseline and 24 hours after FMX infusion.

Drug: Ferumoxytol; Drug: Irinotecan Sucrosofate; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Drug: Veliparib

Interventions

Ferumoxytol DRUG

Given IV

Also known as: Feraheme, Ferumoxytol Non-Stoichiometric Magnetite

Treatment (liposomal irinotecan, veliparib)

Irinotecan Sucrosofate DRUG

Given IV

Also known as: inotecan Hydrochloride as Sucrosulfate Salt Form Liposomal Formulation, Irinotecan Liposome, Irinotecan Sucrosofate Liposome, Irinotecan Sucrosofate-containing Pegylated Liposomal Formulation, MM 398, MM-398, MM398, nal-IRI, Nanoliposomal Irinotecan, Nanoliposomal Irinotecan as Sucrosofate, Nanoparticle Liposome Formulation of Irinotecan, Onivyde, PEP 02, PEP-02, PEP02

Treatment (liposomal irinotecan, veliparib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (liposomal irinotecan, veliparib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (liposomal irinotecan, veliparib)

Veliparib DRUG

Given PO

Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

Treatment (liposomal irinotecan, veliparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have pathologically confirmed diagnosis of a solid tumor cancer for which there is no known standard therapy capable of extending life expectancy
• Prior poly ADP ribose polymerase (PARP) inhibitor therapy is allowed; patients with ovarian cancer and a BRCA mutation should have had prior treatment with olaparib per guidelines for standard of care treatment
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Age \>= 18 years
• Because no dosing or adverse event data are currently available on the use of veliparib in combination with MM-398 in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Hemoglobin \>= 10 g/dL (within 28 days prior to administration of ABT-888)
• Leukocytes \>= 3,000/mcL (within 28 days prior to administration of ABT-888)
• Absolute neutrophil count \>= 1,500/mcL without the use of hematopoietic growth factors (within 28 days prior to administration of ABT-888)
• Platelets \>= 100,000/mcL (within 28 days prior to administration of ABT-888)
• Total bilirubin below institutional upper limit of normal (ULN) (within 28 days prior to administration of ABT-888)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (=\< 5 x ULN is acceptable if liver metastases are present) (within 28 days prior to administration of ABT-888)
• Creatinine =\< 1.5 x ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal (within 28 days prior to administration of ABT-888)
• Based on animal data, MM-398 (ONIVYDETM) and veliparib causes embryo toxicity and teratogenicity; thus, women of childbearing potential and male patients should use effective contraception during treatment with MM-398 and for 90 days following the final dose of veliparib and MM-398 for both female and male patients; 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
• Ability to understand and the willingness to sign a written informed consent document
• IMAGING CORRELATIVE STUDY: Patients will be eligible to participate in the FMX imaging study if the participating study center offers this test and they do not meet any of the following criteria:

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those whose adverse events have not resolved to grade 1 or less (except alopecia) from agents administered more than 4 weeks earlier; patients must have completed prior biological therapies and/or targeted therapies \>= 2 weeks prior to study enrollment; patients who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case by case basis and may be excluded if the bone marrow reserve is not considered adequate (i.e. radiation to \> 25% of bone marrow)
• Patients who are receiving any other investigational agents
• Subjects with symptomatic brain metastases will be excluded from trial secondary to poor prognosis; however, subjects who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for at least 3 months may be enrolled
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib and MM-398; if patients have a history of allergic reactions to compounds resembling MM-398, they will be excluded from participating in the FMX MRI study, if applicable
• Patients who have severe hypersensitivity to irinotecan hydrochloride (HCl)
• Patients with known and confirmed diagnosis of interstitial lung disease (IDL)
• Clinically significant gastrointestinal (GI) disorders, including history of small bowel obstruction unless the obstruction was a surgically treated remote episode
• Patient is unable to swallow or keep down oral medication
• Active infection
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active 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 veliparib, MM-398 and ferumoxytol are agents 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 veliparib, MM-398 and/or ferumoxytol breastfeeding should be discontinued if the mother is treated with any of these agents; these potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with veliparib, MM-398 and/or ferumoxytol; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients who need chronic use of medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible
• Veliparib has a potential seizure risk, therefore patients with a high risk of seizures should be excluded from the protocol (e.g. those patients with an uncontrolled seizure disorder, and/or patients who have had a focal or generalized seizure within the last 12 months
• Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS) or with features suggestive of AML/MDS

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• LaRose M, Connolly RM, O'Sullivan CC, Velcheti V, Vilimas R, Gano K, Bates SE, Pommier Y, Thomas A. A Phase I Study of a Combination of Liposomal Irinotecan and Veliparib in Solid Tumors. Oncologist. 2023 May 8;28(5):460-e298. doi: 10.1093/oncolo/oyad023.

  PMID: 37010988 DERIVED

MeSH Terms

Interventions

Ferrosoferric Oxide; irinotecan sucrosofate; Magnetic Resonance Spectroscopy; veliparib

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Susan E Bates

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 16, 2015
• Study Start: May 31, 2017
• Primary Completion: November 21, 2019
• Study Completion: May 24, 2023
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

US (6)