Clinical Trials /

Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors



The goal of this clinical research study is to learn if ilorasertib (ABT-348) can help to control CDKN2A-deficient cancer. CDKN2A deficiency is a type of mutation (a genetic change). The safety of this drug will also be studied.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting


Phase 2

Trial Eligibility



  • Brief Title: Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors
  • Official Title: A Proof-of-Concept Study for Ilorasertib (ABT-348) Activity in Patients With CDKN2A-Deficient Advanced Solid Cancers: a Phase II Basket Trial

Clinical Trial IDs

  • ORG STUDY ID: 2014-0920
  • SECONDARY ID: NCI-2015-01251
  • NCT ID: NCT02478320


  • Advanced Cancers


IlorasertibABT-348Ilorasertib (ABT-348)


The goal of this clinical research study is to learn if ilorasertib (ABT-348) can help to control CDKN2A-deficient cancer. CDKN2A deficiency is a type of mutation (a genetic change). The safety of this drug will also be studied.

Detailed Description

      Study Drug Administration:

      Each study cycle is 28 days. You will take ABT-348 by mouth 2 times each day on Days 1, 8,
      and 15 of each cycle. The first dose you take on these days is called Dose 1, and the second
      dose you take each day is called Dose 2.

      You will take Dose 1 (the earlier dose) of ABT-348 with 4 ounces (about ½ cup) of water. You
      should fast (not eat or drink anything except water) for 8 hours before taking this dose. You
      need to fast before this dose because eating food may affect the levels of the study drug
      that is able to enter your system. You will be allowed to have a light snack 2 hours after
      Dose 1, and then you may eat anything you like 4 hours after the dose.

      You should take Dose 2 (the later dose) as close as possible to 6 hours after the first dose,
      but not less than 6 hours after the first dose. You do not need to fast before Dose 2. You
      may eat and drink normally around this dose.

      Study Visits:

      On Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2:

        -  You will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests.

        -  You will have an EKG (Day 1 of Cycle 2 only). For Cycle 3 and after, you will have these
           EKGs repeated every 3 cycles (Cycles 6, 9, 12, and so on).

      On Day 1 of all cycles, urine will be collected for routine tests.

      On Day 1 of Cycles 2 and beyond, if you can become pregnant, blood (about 1 teaspoon) or
      urine will be collected for a pregnancy test.

      Every 8 weeks, you will have a chest x-ray, bone scan, MRI/CT or PET/CT to check the status
      of the disease.

      You may be able to have some of these tests/procedures performed at a local lab, clinic, or
      doctor's office that is closer to your home. The results of these tests will be sent to the
      study doctor for review. The study doctor or research staff will discuss this option with you
      in more detail.

      Length of Study Drug Administration:

      You may continue taking the study drug for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drug if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      You participation on this study will be over after your last dose of study drug.

      This is an investigational study. ABT-348 is not FDA approved or commercially available. It
      is currently being used for research purposes only. The study doctor can explain how the
      study drug is designed to work.

      Up to 65 participants will be enrolled in this study. All will take part at MD Anderson.

Trial Arms

Ilorasertib (ABT-348)ExperimentalPart 1 Dose of Ilorasertib: 200 mg administered by mouth twice daily on Days 1, 8, and 15 of each 28-day cycle. Part 2 Expansion: Ilorasertib200 mg administered by mouth twice daily on Days 1, 8, and 15 of each 28-day cycle.
  • Ilorasertib

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with histologically confirmed, advanced or metastatic cancer for which
             standard curative or palliative measures do not exist or are no longer effective.

          2. Patients must have CDKN2A-deficient tumor (deletion or mutation). Definition of CDKN2A
             deficient tumor: #1. CDKN2A deletion or mutation by any CLIA-certified sequencing OR
             #2. >/= 30% of tumor cells with (at least) hemizygous deletion by FISH. Status will be
             determined from archived tissue.

          3. Patients must have measurable disease by RECIST 1.1.

          4. Patients must be >/=18 years of age.

          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.

          6. Subject has adequate renal function as demonstrated by 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 Cockcroft-Gault formula or a creatinine
             clearance value of >/= 50 mL/min based on a 24 hour urine collection.

          7. Subject has adequate liver function as demonstrated by serum bilirubin </= 2 x ULN and
             AST and 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.

          8. Subject has adequate bone marrow as demonstrated by absolute neutrophil count (ANC)
             >/= 1,500/mm3 (1.5 x 10^9/L); Platelets >/= 100,000/mm2 (100 x 10^9/L); Hemoglobin >/=
             9.0 g/dL (1.4 mmol/L).

          9. Subject has QTc interval < 500 msec on baseline electrocardiogram.

         10. The subject has a documented Left Ventricular Ejection Fraction > 50%.

         11. 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/or post menopausal women must be amenorrheic for at least
             12 months to be considered of non-childbearing potential. -Total abstinence from
             sexual intercourse (minimum one complete menstrual cycle) -Vasectomized male subjects
             or vasectomized partner of female subjects -Intrauterine device -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.

         12. Ability to understand and willingness to sign informed consent form prior to
             initiation of the study and any study procedures.

         13. Signed informed consent approved by the Institutional Review Board prior to patient

        Exclusion Criteria:

          1. Patients with CDKN2A wild type by a CLIA-certified laboratory

          2. Subject has known active 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).

          3. Subject has received anti-cancer therapy including chemotherapy, immunotherapy,
             radiotherapy, hormonal, biologic or any investigational therapy within a period of 21
             days or 5 half-lives (whichever is shorter) prior to Study Day 1.

          4. Subject has unresolved toxicities from prior anti-cancer therapy, defined as any
             Common Terminology Criteria for Adverse Events (NCI CTCAE v 4.0) grade 2 or higher
             clinically significant toxicity (excluding alopecia).

          5. Subject has had major surgery within 28 days prior to Study Day 1.

          6. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension
             defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg.
             Subjects may be re-screened if blood pressure is shown to be controlled with or
             without intervention.

          7. Subject has proteinuria defined by the National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI CTCAE 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.

          8. Subject is receiving therapeutic anticoagulation therapy. Low dose anti-coagulation
             (e.g., low dose heparin or warfarin) for catheter prophylaxis will be permitted. Use
             of Aspirin for treatment of Atrial Fibrillation will also be permitted.

          9. Patients with another primary malignancy within 3 years prior to starting study
             treatment with the exception of adequately treated basal cell carcinoma, squamous cell
             carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine

         10. Clinically significant uncontrolled condition(s) including but not limited to: Active
             uncontrolled infection, Symptomatic congestive heart failure, Unstable angina pectoris
             or cardiac arrhythmia (subjects with stable atrial fibrillation are not excluded),
             History of adrenal insufficiency.

         11. Psychiatric illness/social situation that would limit compliance with study

         12. Subject has a known infection with HIV, Hepatitis B or Hepatitis C.

         13. Subject is known to have poorly controlled diabetes mellitus defined as HbA1c > 7%;
             subjects with a history of transient glucose intolerance due to corticosteroid
             administration are allowed in this study if all other inclusion/exclusion criteria are

         14. Any medical condition which in the opinion of the study investigator places the
             subject at an unacceptably high risk for toxicities.

         15. Subject is unable to swallow or absorb oral tablets normally

         16. Female subject who is lactating or pregnant.

         17. Subject takes CYP3A Inhibitors/Inducers within 7 days prior to the study drug
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate of Ilorasertib (ABT-348) in Participants with Cancers Harboring CDKN2A Deletion or Mutation as Tumor Response
Time Frame:56 days
Safety Issue:
Description:Response rate defined as partial response (PR), complete response. (CR). Response and progression evaluated using the new international criteria proposed by revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.

Secondary Outcome Measures

Measure:Toxicities of Ilorasertib (ABT-348)
Time Frame:5 years
Safety Issue:
Description:Toxicities evaluated according to the NCI-CTCAE Version 4.0.
Measure:Pharmacodynamics of Ilorasertib (ABT-348)
Time Frame:5 years
Safety Issue:
Description:Phospho-Histone H3 on biopsied skin tissues analyzed with immunohistochemistry.


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Advanced Cancers
  • CDKN2A-Deficient Advanced Solid Cancers
  • Advanced or metastatic cancer.
  • Ilorasertib
  • ABT-348

Last Updated

October 21, 2019