A Phase I Multiple Ascending Dose Study of ASLAN002 in Subjects With Advanced or Metastatic Solid Tumours

NCT01721148 | Completed Phase 1 DMC

• 1 other identifier: ASLAN002-001
• Study Type: interventional
• Target: 39
• Locations: 0 countries
• Sites: N/A

Brief Summary

There is a great need for new therapies for carcinomas that have progressed on or not responded to current therapy. There are no approved Met targeted agents in standard clinical use. In the population of subjects with advanced carcinomas that are unresponsive to standard of care, and based on the relatively safe, reversible and monitorable toxicity profile of ASLAN002 in non clinical studies, the potential for benefit from ASLAN002 outweighs the potential risks for toxicity. The purpose of this study is to identify the maximum tolerated dose of ASLAN002 in subjects with advanced or metastatic solid tumours, as well as to define the overall safety profile of ASLAN002.

Conditions

Malignant Solid Tumour

Outcome Measures

Primary Outcomes (1)

• To identify the maximum tolerated dose

  MTD is defined as highest dose at which less than 1/3 of the treated subjects experience a DLT (Adverse events, vital signs, electrocardiogram (ECG), echocardiogram scans, serum chemistry, haematology, coagulation factors, urinalysis, ophthalmic examination, and physical examination would be monitored)

  12 months

Secondary Outcomes (2)

• To characterize the pharmacokinetics (PK) of ASLAN002 (BMS-777607) and its N-oxide metabolite, following single and multiple dosing

  12 months

• To provide a preliminary assessment of anti-tumour activity, as assessed by the Overall Response Rate (ORR) and changes from baseline in tumour size

  12 months

Study Arms (1)

Cohort Dose Escalation

OTHER

open label dose escalation study of ASLAN002 administered orally on a once daily schedule to subjects with advanced or metastatic solid tumours, who have either progressed on standard therapy or for whom standard therapy is not known

Drug: ASLAN002( BMS 777607)

Interventions

ASLAN002( BMS 777607) DRUG

100mg, 200mg, 300mg, 450mg, 600mg

Cohort Dose Escalation

Eligibility Criteria

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

You may qualify if:

• Male or female subjects 18 years of age or older at the time of written informed consent is obtained
• Subjects with advanced or metastatic solid tumours who have either progressed on standard therapy or for whom standard therapy is not known
• o Tumour paraffin tissue block or 6-10 unstained slides from the tissue block for biomarker analyses should be provided during screening, if available
• Subjects with histologic or cytologic diagnosis of the solid tumour (non-hematologic) malignancy
• Subjects with life expectancy of at least 2 months
• Subjects with prior anti-cancer treatments are permitted (i.e., chemotherapy, radiotherapy, hormonal, or immunotherapy
• Subjects with toxicity related to prior anti-cancer therapy and/or surgery must either have resolved, returned to baseline or deemed irreversible. Four (4) weeks must have elapsed between surgery and/or last dose of prior anti-cancer therapy and the initiation of study therapy. At least 6 weeks must have elapsed between prior therapy with nitrosoureas, mitomycin C, and liposomal doxorubicin. For biologics (e.g., monoclonal antibodies such as cetuximab) and extended-release formulations, the washout period must extend 1 month beyond the recommended dosing interval (e.g., for cetuximab, once per week + 1 month wash out)
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 28 days prior to enrolment)
• 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 postmenopausal. Post menopausal is defined as:
• Amenorrhea ≥ 12 consecutive months without another cause or
• Irregular menstrual periods and on hormone replacement therapy (HRT), with a documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their 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 gonadotrophin \[HCG\]) within 72 hours prior to the start of investigational product (IP). Sexually active fertile men with partners of childbearing potential must use an approved barrier method of contraception while on study and until at least 3 months after the last dose of IP.
• Subjects with ability to comply with visits/procedures required by the protocol
• Subjects able to provide written informed consent before screening

You may not qualify if:

• Subjects unable to swallow or taken anything orally
• Subjects with significant underlying cardiac disease including ischaemic heart disease (New York Heart Association \[NYHA\] class III-IV severity) and prior myocardial infarction, or uncontrolled angina within 6 months of study entry
• Congestive cardiac failure within 3 months of study entry
• Documented prior history, or evidence of symptomatic orthostatic hypotension (e.g., orthostatic dizziness or light headedness) at screening
• Uncontrolled hypertension requiring treatment with calcium-channel antagonists or beta-blockers.
• Subjects requiring treatment for arrhythmias including atrial fibrillation, supraventricular tachycardia and previous episodes of ventricular tachycardia or fibrillation
• ECG abnormalities as confirmed by Holter monitoring Episodes of ventricular tachycardia or paroxysmal atrial fibrillation (to be reviewed by Principal Investigator and cardiologist)
• Subjects receiving beta-blockers, calcium-channel antagonists or Class IV anti-arrhythmic drugs including sotalol or amiodarone
• Subjects with known symptomatic brain metastasis. Subjects with controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment and no neurological signs or symptoms) will be allowed.
• A serious uncontrolled medical disorder or active infection, which would impair the ability of the subject to receive protocol therapy.
• Current or recent (within 3 months) gastrointestinal disease that could impact the absorption of IP (i.e., unmanageable diarrhoea or malabsorption at the time of screening).
• Inadequate laboratory findings:
• Inadequate bone marrow function defined as:
• Absolute neutrophil count \< 1,500 cells/mm3 Platelet count \< 100,000 cells/mm3 Haemoglobin \< 9 g/dL Inadequate hepatic function Inadequate renal function Prothrombin time international normalized ration)/partial thromboplastin time \> 1.5 times the ULN Serum sodium, potassium, calcium and magnesium levels equivalent to Grade 1 AE values as defined by Common Terminology Criteria for Adverse Events version 4.0
• Any atrophic macular condition including intermediate or advanced age-related macular degeneration

Sponsors & Collaborators

• ASLAN Pharmaceuticals: lead

Related Publications (1)

• Roohullah A, Cooper A, Lomax AJ, Aung J, Barge A, Chow L, McHale M, Desai J, Whittle JR, Tran B, de Souza P, Horvath LG. A phase I trial to determine safety and pharmacokinetics of ASLAN002, an oral MET superfamily kinase inhibitor, in patients with advanced or metastatic solid cancers. Invest New Drugs. 2018 Oct;36(5):886-894. doi: 10.1007/s10637-018-0588-7. Epub 2018 May 16.

  PMID: 29766337 DERIVED

Study Officials

• Please contact ASLAN Pharmaceuticals Pte Ltd

  contact@aslanpharma.com

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 5, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 25, 2017

Record last verified: 2017-01