Clinical Trials /

Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors

NCT02631733

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Cervical Carcinoma
  • Gastric Carcinoma
  • Neuroendocrine Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Liposomal Irinotecan</span> and Veliparib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Title

  • Brief Title: Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
  • Official Title: A Phase I Study of a Combination of MM-398 and Veliparib in Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02631733

    ORG ID: NCI-2015-02125

    NCI ID: NCI-2015-02125

    Trial Conditions

    Estrogen Receptor Negative

    HER2/Neu Negative

    Neuroendocrine Neoplasm

    Progesterone Receptor Negative

    Stage IIB Cervical Cancer

    Stage IIIA Cervical Cancer

    Stage IIIB Cervical Cancer

    Stage IIIB Non-Small Cell Lung Cancer

    Stage IIIC Breast Cancer

    Stage IV Breast Cancer

    Stage IV Cervical Cancer

    Stage IV Gastric Cancer

    Stage IV Non-Small Cell Lung Cancer

    Stage IV Ovarian Cancer

    Stage IV Small Cell Lung Carcinoma

    Triple-Negative Breast Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Ferumoxytol Feraheme, FERUMOXYTOL NON-STOICHIOMETRIC MAGNETITE Treatment (liposomal irinotecan, veliparib)
    Liposomal Irinotecan Irinotecan Liposome, Onivyde, PEP02 Treatment (liposomal irinotecan, veliparib)
    Veliparib ABT-888, PARP-1 inhibitor ABT-888 Treatment (liposomal irinotecan, veliparib)

    Trial Purpose

    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 that have spread to other
    parts of the body (metastatic) or cannot be removed by surgery. Liposomal irinotecan and
    veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
    growth.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To evaluate the safety and tolerability of escalating doses of MM-398 (liposomal
    irinotecan) + 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 correlation with clinical response.

    OUTLINE: This is a dose-escalation of veliparib.

    Patients receive liposomal irinotecan intravenously (IV) over 90 minutes on days 1 and 15
    and veliparib orally (PO) 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.

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

    Trial Arms

    Name Type Description Interventions
    Treatment (liposomal irinotecan, veliparib) Experimental Patients receive liposomal irinotecan IV over 90 minutes on days 1 and 15 and veliparib PO 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. Ferumoxytol, Liposomal Irinotecan, Veliparib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have pathologically confirmed diagnosis of one of the following solid
    tumors: cervical cancer, ovarian cancer, triple negative breast cancer (TNBC),
    non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric cancer,
    and neuroendocrine tumors that is metastatic or unresectable and for which standard
    curative or palliative measures do not exist or are no longer effective

    - Prior poly ADP ribose polymerase (PARP) inhibitor therapy is allowed

    - Patients at the National Cancer Institute (NCI) site must be willing to undergo a
    pre-treatment ferumoxytol magnetic resonance imaging (MRI) (patients will be excluded
    from undergoing ferumoxytol MRI if they 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 eligibility
    criterion applies only to patients enrolling at NCI

    - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

    - Life expectancy of greater than 3 months

    - 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 within normal institutional limits

    - 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 upper limit of normal [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 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; men and women 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 veliparib, MM-398
    and ferumoxytol MRI administration

    - Ability to understand and the willingness to sign a written informed consent document

    - IMAGING CORRELATIVE STUDY: Patients will be eligible to participate in the
    ferumoxytol (FMX) imaging study if 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 who have not
    recovered from adverse events due to 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

    - Patients with active brain metastases should be excluded from this clinical trial

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to veliparib, MM-398 and ferumoxytol

    - Clinically significant gastrointestinal (GI) disorders, including history of small
    bowel obstruction unless the obstruction was a surgically treated remote episode

    - 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

    - Patients who are taking medications which are strong inhibitors or inducers of
    cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of adverse events, graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    MTD and RP2D of liposomal irinotecan in combination with veliparib determined by incidence of dose limiting toxicities, graded using the NCI CTCAE version 4.0

    Secondary Outcome Measures

    Clinical benefit rate defined as CR, PR, or SD assessed using RECIST version 1.1

    Objective response rate assessed using RECIST version 1.1

    PFS

    Tumor response assessed using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

    Trial Keywords