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Malignant Solid NeoplasmPhase 1NCT02631733

Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors

A Phase 1 study testing Ferumoxytol, Irinotecan Sucrosofate and Laboratory Biomarker Analysis in people with Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Solid Neoplasm
What is being tested?
Ferumoxytol, Irinotecan Sucrosofate and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
6 sitesUnited States
Study dates
31 May 2017to 24 May 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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:
  • Evidence of iron overload as determined by:
  • Fasting transferrin saturation of > 45% and/or
  • Serum ferritin levels > 1000 ng/ml
  • A history of allergic reactions to any of the following:
  • Compounds similar to ferumoxytol or any of its components as described in full prescribing information for ferumoxytol injection
  • Any IV iron replacement product (e.g. parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations)
  • Multiple drugs
  • Unable to undergo MRI or for whom MRI is otherwise contraindicated (e.g. presence of errant metal, cardiac pacemakers, pain pumps or other MRI incompatible devices; or history claustrophobia or anxiety related to undergoing MRI)

Who cannot join

  • 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)
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  • 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
  • Patients at the National Cancer Institute (NCI) site and other selected centers who are willing to undergo an optional pre-treatment ferumoxytol MRI must not have evidence of iron overload, a known hypersensitivity to ferumoxytol or any other IV iron product, a documented history of multiple drug allergies, or those for whom MRI is otherwise contraindicated, including claustrophobia or anxiety related to undergoing MRI; this exclusion criterion applies only to patients enrolling at NCI and other selected sites; of note, the principal investigator (PI) will allow other centers to offer FMX MRI scans if the site in question is willing and the site PI can identify the necessary resources and expertise at their center
  • 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
  • Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • NCI - Center for Cancer Research

    Bethesda, Maryland, 20892

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

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

    New York, New York, 10032

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I Study of a Combination of MM-398 and Veliparib in Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of escalating doses of liposomal irinotecan (MM-398) + veliparib combination.

II. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of MM-398 + veliparib.

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity. II. To characterize the preliminary efficacy of the combination using key efficacy indicators, such as objective response rate, clinical benefit rate defined as complete response (CR), partial response (PR), or stable disease (SD) at 24 weeks, and progression free survival (PFS).

EXPLORATORY OBJECTIVE:

  1. Imaging, tumor, and blood biomarkers to assess the sensitivity or resistance to each drug and/or correlation with clinical response.

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive liposomal irinotecan intravenously (IV) over 90 minutes on days 1 and 15 and veliparib orally (PO) twice daily (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 ferumoxytol (FMX) IV and undergo magnetic resonance imaging (MRI) at baseline and 24 hours after FMX infusion.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
Ferumoxytol, Irinotecan Sucrosofate, Laboratory Biomarker Analysis, Magnetic Resonance Imaging, Veliparib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FerumoxytolDrug

    Also called Feraheme, Ferumoxytol Non-Stoichiometric Magnetite

    Given IV

  • Irinotecan SucrosofateDrug

    Also called inotecan Hydrochloride as Sucrosulfate Salt Form Liposomal Formulation, Irinotecan Liposome, Irinotecan Sucrosofate Liposome, Irinotecan Sucrosofate-containing Pegylated Liposomal Formulation

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • VeliparibDrug

    Also called ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT02631733
Study groupRoleWhat they receive
Treatment (liposomal irinotecan, veliparib)ExperimentalPatients 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.
Receives: Drug: Ferumoxytol; Drug: Irinotecan Sucrosofate; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Drug: Veliparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 4 weeks

  2. 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).

    Measured: At 28 days

Secondary outcomes (4)

  1. Tumor response

    Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.

    Measured: Up to 4 weeks after completion of study treatment

  2. Objective response rate

    Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.

    Measured: At 24 weeks

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

    Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.

    Measured: At 24 weeks

  4. Progression free survival

    Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2015 (estimated)
  2. Study start31 May 2017
  3. Primary completion21 Nov 2019
  4. Study completion24 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02631733
Sponsor's protocol ID
NCI-2015-02125
Other IDs
NCI-2015-02125, 17-C-0012, 9914, 9914, ZIABC011078
Status last verified
Feb 2025
First submitted
15 Dec 2015
Last updated
10 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37010988

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ferumoxytol, Irinotecan Sucrosofate and Laboratory Biomarker Analysis in people with Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02631733, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.

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