Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2024
• Main ID: NCT02631733
• Date of registration: 15/12/2015
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors
• Scientific title: A Phase I Study of a Combination of MM-398 and Veliparib in Solid Tumors
• Date of first enrolment: May 31, 2017
• Target sample size: 48
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02631733
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Susan E Bates
• Affiliation: Yale University Cancer Center LAO

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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:

- 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)

Exclusion Criteria:

- 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

- 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Malignant Solid Neoplasm

Intervention(s)

Other: Laboratory Biomarker Analysis

Drug: Irinotecan Sucrosofate

Procedure: Magnetic Resonance Imaging

Drug: Ferumoxytol

Drug: Veliparib

Primary Outcome(s)

Maximum tolerated dose and recommended phase II dose of liposomal irinotecan in combination with veliparib [Time Frame: At 28 days]

Incidence of adverse events [Time Frame: Up to 4 weeks]

Secondary Outcome(s)

Objective response rate [Time Frame: At 24 weeks]

Clinical benefit rate defined as complete response, partial response, or stable disease [Time Frame: At 24 weeks]

Progression free survival [Time Frame: 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]

Tumor response [Time Frame: Up to 4 weeks after completion of study treatment]

Secondary ID(s)

ZIABC011078

17-C-0012

9914

NCI-2015-02125

Source(s) of Monetary Support

Please refer to primary and secondary sponsors