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

NCT01049893 | Completed Phase 1

• 1 other identifier: AC220-004
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

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

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

Secondary Outcomes (2)

• 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

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

• 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 every 28 days (per treatment cycle)

Study Arms (1)

AC220

EXPERIMENTAL

Dose finding study. Number of arms dependant upon dose limiting toxicities.

Drug: Compound AC220

Interventions

Compound AC220 DRUG

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.

Also known as: AC010220 * 2HCl, oral powder for reconstitution

AC220

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 30081867 DERIVED

MeSH Terms

Interventions

quizartinib; Powders

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Guy Gammon, MB BS, MRCP

  Interim Chief Medical Officer, Ambit Biosciences Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2010
• First Posted: January 15, 2010
• Study Start: January 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: February 12, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (2)