ClinicalTrials.gov
ClinicalTrials.gov Menu

Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02631733
Recruitment Status : Recruiting
First Posted : December 16, 2015
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Malignant Solid Neoplasm Drug: Ferumoxytol Other: Laboratory Biomarker Analysis Drug: Liposomal Irinotecan Procedure: Magnetic Resonance Imaging Drug: Veliparib Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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 OBJECTIVES I. 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. Courses 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of a Combination of MM-398 and Veliparib in Solid Tumors
Actual Study Start Date : July 15, 2016
Estimated Primary Completion Date : July 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (liposomal irinotecan, veliparib)
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. Courses 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
Given IV
Other Names:
  • Feraheme
  • Ferumoxytol Non-Stoichiometric Magnetite

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Liposomal Irinotecan
Given IV
Other Names:
  • Irinotecan Liposome
  • MM-398
  • nal-IRI
  • Nanoliposomal Irinotecan
  • Nanoparticle Liposome Formulation of Irinotecan
  • Onivyde
  • PEP02

Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888




Primary Outcome Measures :
  1. Incidence of adverse events, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018) [ Time Frame: Up to 4 weeks ]
    Safety and tolerability of escalating doses of liposomal irinotecan and veliparib combination will be evaluated.

  2. Maximum tolerated dose and recommended phase II dose of liposomal irinotecan in combination with veliparib evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018) [ Time Frame: At 28 days ]
    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).


Secondary Outcome Measures :
  1. Tumor response assessed using the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1) [ Time Frame: Up to 4 weeks after completion of study treatment ]
    Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.

  2. Objective response rate assessed using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: At 24 weeks ]
    Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.

  3. Clinical benefit rate defined as complete response, partial response, or stable disease assessed using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: At 24 weeks ]
    Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.

  4. 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 ]
    Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.


Other Outcome Measures:
  1. Biomarker levels [ Time Frame: Up to 4 weeks after completion of study treatment ]
    Will be studied to assess the sensitivity or resistance to each drug and correlated with clinical response.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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%)
  • Hemoglobin > 9 g/dL
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL without the use of hematopoietic growth factors
  • Platelets >= 100,000/mcL
  • Total bilirubin below normal institutional upper limit of normal (ULN)
  • 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)
  • Creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • 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; breastfeeding should be discontinued if the mother is treated with any of these agents
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; 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
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02631733


Locations
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Site Public Contact    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Roisin M. Connolly         
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Site Public Contact    800-411-1222      
Principal Investigator: Anish Thomas         
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Site Public Contact    800-411-1222      
Principal Investigator: Anish Thomas         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Site Public Contact    855-776-0015      
Principal Investigator: Ciara C. O'Sullivan         
United States, New York
Columbia University/Herbert Irving Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Site Public Contact    212-305-6361    nr2616@cumc.columbia.edu   
Principal Investigator: Susan E. Bates         
United States, Ohio
Cleveland Clinic Foundation Suspended
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Anish Thomas National Cancer Institute LAO

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02631733     History of Changes
Other Study ID Numbers: NCI-2015-02125
NCI-2015-02125 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-C-0012
9914 ( Other Identifier: National Cancer Institute LAO )
9914 ( Other Identifier: CTEP )
ZIABC011078 ( U.S. NIH Grant/Contract )
First Posted: December 16, 2015    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: August 2018

Additional relevant MeSH terms:
Irinotecan
Camptothecin
Veliparib
Ferrosoferric Oxide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions