AzTrials
AzTrials

Advanced CancersPhase 2NCT02478320

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

A Phase 2 study testing Ilorasertib in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Cancers
What is being tested?
Ilorasertib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
5 Aug 2016to 12 May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically confirmed, advanced or metastatic cancer for which standard curative or palliative measures do not exist or are no longer effective.
  • 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.
  • Patients must have measurable disease by RECIST 1.1.
  • Patients must be >/=18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
  • 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.
Show all 13Show fewer
  • 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.
  • 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).
  • Subject has QTc interval < 500 msec on baseline electrocardiogram.
  • The 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/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.
  • Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.
  • Signed informed consent approved by the Institutional Review Board prior to patient entry

Who cannot join

  • Patients with CDKN2A wild type by a CLIA-certified laboratory
  • 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).
  • 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.
  • 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).
  • Subject has had major surgery within 28 days prior to Study Day 1.
  • 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.
Show all 17Show fewer
  • 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.
  • 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.
  • 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 cervix.
  • 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.
  • Psychiatric illness/social situation that would limit compliance with study requirements.
  • Subject has a known infection with HIV, Hepatitis B or Hepatitis C.
  • 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 met.
  • Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities.
  • Subject is unable to swallow or absorb oral tablets normally
  • Female subject who is lactating or pregnant.
  • Subject takes CYP3A Inhibitors/Inducers within 7 days prior to the study drug administration.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Ilorasertib
Keywords
Advanced Cancers, CDKN2A-Deficient Advanced Solid Cancers, Advanced or metastatic cancer., Ilorasertib, ABT-348
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IlorasertibDrug

    Also called ABT-348

    200 mg administered by mouth twice daily on Days 1, 8, and 15 of each 28-day cycle.

Study groups in NCT02478320
Study groupRoleWhat they receive
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.
Receives: Drug: Ilorasertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response Rate

    Partial or complete response to ilorasertib

    Measured: through study completion, maximum 18 months

  2. Efficacy Signal

    Selection of specific tumor type where the drug is potentially active for recruitment of additional patients (expansion)

    Measured: through study completion, maximum 18 months

Secondary outcomes (2)

  1. Safety and Tolerability

    Safety and tolerability of ilorasertib.

    Measured: through study completion, maximum 18 months'

  2. Pharmacodynamic Activity

    Assessment of the pharmacodynamic effects of ilorasertib by immunohistochemistry for phospho-histone H3

    Measured: Cycle 1 Day 1 at up to 72 hours prior to the first dose and 2-4 hours after the second dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2015 (estimated)
  2. Study start5 Aug 2016
  3. Primary completion12 May 2022
  4. Study completion12 May 2022

Why it stopped: Study terminated due to company's decision to discontinue drug development

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02478320
Sponsor's protocol ID
2014-0920
Other IDs
NCI-2015-01251
Status last verified
Jul 2023
First submitted
19 Jun 2015
Last updated
17 Jul 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ilorasertib in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (time frame: through study completion, maximum 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02478320.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in