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Solid TumorsPhase 1NCT01049893

Dose Finding, Safety and Tolerability Study for AC220 to Treat Advanced Solid Tumors

A Phase 1 study testing Compound AC220 in people with Solid Tumors, run by Daiichi Sankyo at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without food and without any rest periods, as long as there is no evidence of disease progression or unacceptably severe adverse events (AEs) related to the study drug. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
Compound AC220
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
2 sitesUnited States
Study dates
Jan 2010to Nov 2011
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Males and females age ≥18 years
  • Understand and voluntarily sign the informed consent form for this study
  • Available for periodic follow-up at the investigative site
  • Able to swallow the liquid study drug
  • ECOG performance status of 0 - 2
  • Histological diagnosis of a primary solid tumor malignancy that meets the following criteria:
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  • Evidence (radiographic or tissue confirmation) that the disease is metastatic (locally advanced disease is allowable only if no surgical or local therapeutic option exists); and
  • Disease which has progressed on or following currently available standard therapies or for which no curative therapy exists (Prior adjuvant, neoadjuvant, and investigational therapies are permitted.)
  • Measurable disease by computer tomography (CT) or magnetic resonance imaging (MRI) scans per RECIST.
  • Prior anticancer therapy, radiotherapy, hormonal, and immunotherapy are allowed. Patients must have recovered from toxicity of prior therapy (ie, toxicity has resolved to Grade 1, or to pre-treatment baseline, or is deemed irreversible). At least 4 weeks must have elapsed since the last systemic therapy (6 weeks for nitrosoureas, mitomycin-C, and liposomal doxorubicin), immunotherapy, or radiotherapy and the beginning of study drug administration. For participants with GIST on approved tyrosine kinase inhibitors (TKI), at least 2 weeks must have elapsed since the last dose of TKI.
  • Adequate bone marrow function, defined as:
  • Absolute neutrophil count (ANC) (neutrophils and bands) ≥1.5 x 10^9 cells/L
  • Platelet count ≥ 100 x 10^9 cells/L
  • Hemoglobin ≥ 9.0 g/dL
  • Adequate hepatic function, defined as:
  • Total serum bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x the institutional ULN
  • Adequate renal function, defined as:
  • Serum creatinine ≤ 1.5 x the institutional ULN
  • Prothrombin time or partial thromboplastin time (PT- PTT) ≤ 1.5 x the ULN
  • Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits, and every effort should be made to keep potassium concentrations above 4.0 mEq/dL, magnesium concentrations above 1.8 mg/dL, and serum calcium at normal concentration with the administration of oral/IV potassium and/or magnesium and/or calcium replacement during the study. If this is not possible, potassium and magnesium (and calcium) concentrations should at least be kept within institutional normal limits.
  • Fully recovered (≤ Grade 1 or returned to baseline or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug administration.
  • Baseline left ventricular ejection fraction (LVEF) ≥ 45% (or ≥ institutional lower limit of normal if institutional lower limit of normal is below 45%) as assessed by 2-dimensional ECHO or MUGA as per institutional practice. If repeat LVEF assessment is required, the same modality should be used throughout the duration of study, whenever possible.
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 3 months after the study in such a manner that the risk of pregnancy is minimized. WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not post menopausal (defined as amenorrhea > 12 consecutive months; or who is on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL). Additionally, premenopausal women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, are practicing abstinence, or whose partner is sterile (eg, vasectomy), should be considered to be of childbearing potential.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 72 hours prior to the start of study drug.

Who cannot join

  • WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy for the entire study period and for at least 3 months after the study.
  • Women who are pregnant or breastfeeding
  • WOCBP with a positive pregnancy test on enrollment prior to study drug administration
  • Men who are unwilling or unable to use an acceptable method of birth control if their sexual partners are WOCBP for the entire study period and for at least 3 months after completion of the study
  • Patients with known untreated, symptomatic or uncontrolled brain or central nervous system (CNS) metastases. Patients with treated brain or CNS metastases that are radiographically stable for 3 months or longer are eligible.
  • A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive study drug
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  • Uncontrolled or significant cardiovascular disease, including:
  • A myocardial infarction within 12 months prior to study entry
  • Uncontrolled angina within 6 months prior to study entry
  • Congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4, or patients with history CHF NYHA class 3 or 4 in the past, unless the screening ECHO or MUGA within 14 days prior to study entry results in a LVEF that is ≥ 45% (or ≥institutional lower limit of normal)
  • Diagnosed or suspected congenital long QT syndrome
  • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes [TdP])
  • Prolonged QTc interval on pre-entry ECG (≥ 450 ms)
  • Any history of second or third degree heart block
  • Uncontrolled hypertension
  • Obligate need for a cardiac pacemaker
  • Complete left bundle branch block
  • Atrial fibrillation
  • Known infection with human immunodeficiency virus (HIV)
  • Known active hepatitis A, B, or C or other active liver disease
  • Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
  • Investigational agents during or within 4 weeks prior to the start of study drug
  • Use of drugs that are generally accepted to have a risk of causing prolonged QTc and/or TdP and/or are CYP3A4 inhibitors. Patients who have discontinued any of these medications must have a washout period of at least 5 days or at least 5 half-lives of the drug (whichever is greater) prior to the first dose of study drug and should not be allowed to take these medications during the study drug dosing.
  • Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator or Sponsor, could jeopardize patient safety or interfere with the objectives of the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • South Texas Accelerated Research Therapeutics (START)

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Phase 1 Open-Label, Dose Finding, Safety and Tolerability Study of AC220 Administered Daily to Patients With Advanced Solid Tumors

AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without food and without any rest periods, as long as there is no evidence of disease progression or unacceptably severe adverse events (AEs) related to the study drug.

Read the detailed description

A phase 1 open-label, dose finding study of AC220 in patients with solid tumors.

Conditions
Solid Tumors
Being tested
Compound AC220

What participants receive

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

  • Compound AC220Drug

    Also called AC010220 * 2HCl, oral powder for reconstitution

    Precomplexed powder in bottle formulation supplied as 135 mg in a 60 cc polyethylene terephthalate (PET) plastic bottle. Requires reconstitution by a pharmacist, must be stored securely, and protected from light.

Study groups in NCT01049893
Study groupRoleWhat they receive
AC220ExperimentalDose finding study. Number of arms dependant upon dose limiting toxicities.
Receives: Drug: Compound AC220

What is being measured

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

  1. Safety and tolerability of AC220 given once daily without food continuously for 28 days (1 cycle) to patients with advanced solid tumors.

    Measured: Repeatedly measured at multiple timepoints during 1st cycle; every 2 weeks thereafter

Secondary outcomes (2)

  1. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters of AC220 in this patient population under the conditions of the study, including a careful and detailed evaluation of the ECG effects of AC220 in relation to plasma drug concentration

    Measured: Repeatedly measured at multiple timepoints during the first cycle of treament.

  2. Preliminary evidence of antitumor biology or clinical activity of AC220 in patients enriched for diseases whose pathophysiology is directly related to aberrant c-KIT receptor or platelet-derived growth factor receptor signaling.

    Measured: Measured every 28 days (per treatment cycle)

Timeline

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

  1. First posted15 Jan 2010 (estimated)
  2. Study startJan 2010
  3. Primary completionNov 2011
  4. Study completionNov 2011

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01049893
Sponsor's protocol ID
AC220-004
Status last verified
Dec 2018
First submitted
13 Jan 2010
Last updated
12 Feb 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Publications

  • Papadopoulos KP, Ben-Ami E, Patnaik A, Trone D, Li J, Demetri GD. Safety and tolerability of quizartinib, a FLT3 inhibitor, in advanced solid tumors: a phase 1 dose-escalation trial. BMC Cancer. 2018 Aug 6;18(1):790. doi: 10.1186/s12885-018-4692-z.

    PubMed 30081867

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Compound AC220 in people with Solid Tumors, run by Daiichi Sankyo at 2 sites 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 25 inclusion and 24 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: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and tolerability of AC220 given once daily without food continuously for 28 days (1 cycle) to patients with advanced solid tumors. (time frame: Repeatedly measured at multiple timepoints during 1st cycle; every 2 weeks thereafter). 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 NCT01049893, which also lists 1 linked publication.

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 12 Feb 2019.

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