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

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

  • ORG STUDY ID: IRB15-0083
  • SECONDARY ID: NCI-2015-01328
  • SECONDARY ID: AbbVie IIS-10750
  • SECONDARY ID: IRB15-0083
  • SECONDARY ID: P30CA014599
  • NCT ID: NCT02540876

Conditions

  • Metastatic Malignant Neoplasm
  • Solid Neoplasm
  • Unresectable Malignant Neoplasm

Interventions

DrugSynonymsArms
IlorasertibA-968660.0, ABT-348Treatment (ilorasertib)

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.

Trial Arms

NameTypeDescriptionInterventions
Treatment (ilorasertib)ExperimentalPatients 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in tumor burden.
Time Frame:22 weeks
Safety Issue:
Description:Change in tumor measurements from baselines through end of study.

Secondary Outcome Measures

Measure:Number of patients with response as per Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame:Up to week 12
Safety Issue:
Description:The number of patients with RECIST response will be estimated at week 12.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:University of Chicago

Last Updated

April 22, 2019