Clinical Trials /

Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery

NCT02540876

Description:

This pilot phase I trial studies how well ilorasertib works in treating patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-deficient solid cancers that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic) and cannot be removed by surgery. Ilorasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ilorasertib</span> in Treating Patients With <span class="go-doc-concept go-doc-biomarker">CDKN2A</span>-<span class="go-doc-concept go-doc-keyword">deficient</span> Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery

Title

  • Brief Title: Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery
  • Official Title: A Pilot Study for Ilorasertib (ABT-348) in Patients With CDKN2A-deficient Advanced Solid Cancers: A Series of Individual Patient Cross-Over Studies With Growth Trajectory Assessment
  • Clinical Trial IDs

    NCT ID: NCT02540876

    ORG ID: IRB15-0083

    NCI ID: NCI-2015-01328

    Trial Conditions

    Metastatic Malignant Neoplasm

    Solid Neoplasm

    Unresectable Malignant Neoplasm

    Trial Interventions

    Drug Synonyms Arms
    Ilorasertib A-968660.0, ABT-348 Treatment (ilorasertib)

    Trial Purpose

    This pilot phase I trial studies how well ilorasertib works in treating patients with
    cyclin-dependent kinase inhibitor 2A (CDKN2A)-deficient solid cancers that have spread to
    other places in the body and usually cannot be cured or controlled with treatment (advanced)
    or have spread to other places in the body (metastatic) and cannot be removed by surgery.
    Ilorasertib may stop the growth of tumor cells by blocking some of the enzymes needed for
    cell growth.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To perform serial tumor volume-based growth trajectory assessments in the setting of a
    candidate therapeutic in a molecularly defined subset of advanced cancer patients.

    II. To enable patients and physicians to make informed and individualized assessments of
    ilorasertib treatment effects on CDKN2A-deficient tumors.

    III. To develop new technologies of quantitative measurements of plasma tumor
    deoxyribonucleic acid (DNA) and computed tomography (CT) imaging volume measurements as
    methods to evaluate treatment effects on advanced solid tumors.

    IV. To generate descriptive, proof-of-concept data to inform further investigation of
    ilorasertib in solid tumors.

    OUTLINE:

    Patients receive ilorasertib orally (PO) twice daily (BID) on days 1, 8, 15, 29, and 36.
    Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or
    unacceptable toxicity.

    After completion of study treatment, patients are followed up for 30 days.

    Trial Arms

    Name Type Description Interventions
    Treatment (ilorasertib) Experimental Patients receive ilorasertib PO BID on days 1, 8, 15, 29, and 36. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Ilorasertib

    Eligibility Criteria

    Inclusion Criteria:

    - Eligible and consent to the Institutional Review Board (IRB) 13-0002 registry trial
    protocol

    - Subjects must have histologically confirmed solid malignancy that is metastatic or
    unresectable

    - The patient should have received all established therapies where there is a clear,
    superior available regimen available for the patient and the patient should have
    demonstrated progressive disease on or since completion of the last treatment regimen

    - Patients must have measurable disease defined as lesions that can be accurately
    measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with
    conventional techniques or as >= 1 cm with spiral CT scan

    - Patients must have prior CT scan images available for investigators to collect

    - Patients must have available tumor molecular profiling from Clinical Laboratory
    Improvement Amendments (CLIA)-certified labs or have available archived tissue to be
    sent to such a laboratory in the context of this investigation

    - Molecular testing in a CLIA-certified laboratory must have demonstrated a deletion
    involving the CDKN2A locus or a mutation within the locus that can be deemed from
    best available evidence to be likely to cause inactivation of a gene within or
    protein encoded by CDKN2A; sequencing or fluorescence in situ hybridization
    (FISH)/chromogenic in situ hybridization (CISH) methods are acceptable; the
    investigators will consider analyses performed according to similar standards as
    applied by Foundation Medicine (likely to be the most common source of molecular
    diagnostic data for patients in this trial)

    - At least 3 weeks must have passed since any prior anti-tumor therapies including
    chemotherapy, radiation therapy or any other anti-cancer treatments

    - Serum creatinine value of < 1.5 times the upper limit of normal (ULN) and either an
    estimated creatinine clearance value of > 50 mL/min as determined by the Chronic
    Kidney Disease Epidemiology (CKD EPI) or MDRD (Modification of Diet in Renal Disease)
    formulae or a creatinine clearance value of > 50 mL/min based on a 24 hour urine
    collection

    - Subject has adequate liver function as demonstrated by serum bilirubin < 2 x ULN and
    Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN. For
    subjects with liver metastasis, adequate liver function is demonstrated by serum
    bilirubin =< 2 x ULN and AST/ALT =< 5.0 x ULN

    - Subject has adequate bone marrow as demonstrated by absolute neutrophil count (ANC)
    >= 1,500/mm^3 (1.5 x 10^9/L); platelets >= 100,000/mm^2 (100 x 10^9/L); hemoglobin >=
    9.0 g/dL (1.4 mmol/L)

    - Subject has QTc interval < 500 msec on baseline electrocardiogram

    - Subject has blood pressure controlled to < 150 mmHg systolic and < 95 mmHg diastolic
    at screening

    - Subject has a documented left ventricular ejection fraction > 50%

    - Women of child-bearing potential and men must agree to use adequate contraception
    (one of the following listed below) prior to the study entry, for the duration of
    study participation and up to 3 months following completion of therapy; women of
    child-bearing potential must have a negative pregnancy test within 7 days prior to
    initiation of treatment and post-menopausal women must be amenorrheic for at least 12
    months to be considered of non-childbearing potential

    - Acceptable contraception

    - Total abstinence from sexual intercourse (minimum one complete menstrual
    cycle)

    - Vasectomized male subjects or vasectomized partner of female subjects

    - Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
    ring with spermicidal jellies or cream)

    - Additionally, male subjects (including those who are vasectomized) whose
    partners are pregnant or might be pregnant must agree to use condoms for
    the duration of the study and for 3 months following completion of therapy

    - Eastern Cooperative Oncology Group (ECOG) performance status: 0-1

    - Patients must be able to provide written informed consent

    Exclusion Criteria:

    - Patients with hospitalization within 4 weeks of treatment initiation date for
    co-morbid conditions or any complication of disease or therapy that is deemed by the
    principal investigator as unstable or incompletely treated

    - Patients with any psychiatric or social condition that leads them to be unlikely to
    adhere to the study schedule and contribute to the primary objectives

    - Women that are pregnant or lactating are excluded from this study

    - Subject has known active central nervous system (CNS) involvement; the subject has
    untreated brain or meningeal metastases; CT scans are not required to rule out brain
    or meningeal metastases unless there is a clinical suspicion of central nervous
    system disease; subjects with treated brain metastases that are radiographically or
    clinically stable for at least 4 weeks after therapy and have no evidence of
    cavitation or hemorrhage in the brain lesion(s) are eligible, providing that they are
    asymptomatic, and do not require corticosteroids (must have discontinued steroids at
    least 1 week prior to study drug administration)

    - Subject has had major surgery within 28 days prior to study day 1

    - Subject has proteinuria defined by the National Cancer Institute Common Terminology
    Criteria for Adverse Events (NCI CTCAE version [v] 4.0) grade > 1 at baseline as
    measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine
    collection (>= 1 g/24 hrs); subjects may be re-screened if proteinuria is shown to be
    controlled with or without intervention

    - Subject is taking any oral anticoagulant

    - History of:

    - Symptomatic congestive heart failure

    - Unstable angina pectoris or cardiac arrhythmia (subjects with stable atrial
    fibrillation are not excluded)

    - Adrenal insufficiency

    - Subject is unable to swallow or absorb oral tablets normally

    - Subject takes cytochrome P450, family 3, subfamily A (CYP3A) inhibitors within 3 days
    or inducers within 7 days prior to the study drug administration; any questions or
    clarifications of these determinations should be brought to the attention of the
    principal investigator (PI); the PI will make the final determination on when it is
    safe to initiate ABT-348 (ilorasertib) therapy under circumstances where the
    magnitude or relevance of possible CYP3A4 inhibitors/inducers is unclear in the
    protocol appendix

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Change in tumor burden.

    Secondary Outcome Measures

    Number of patients with response as per Response Evaluation Criteria in Solid Tumors (RECIST).

    Trial Keywords