Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-FU or Cisplatin and Capecitabine

October 24, 2018 updated by: ASLAN Pharmaceuticals

Phase I Study to Evaluate the Safety and Tolerability of ASLAN001 in Combination With Cisplatin and 5-Fluorouracil or Cisplatin and Capecitabine

This is a phase IB study to assess the safety and tolerability of ASLAN001 when given in combination with either Cisplatin and 5-Fluorouracil or Cisplatin and Capecitabine, with a view to identifying the recommended Phase II dose.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, Phase I, dose escalation study of ASLAN001 given in combination with Regimen A or Regimen B, in patients with metastatic solid tumors, eligible to receive the cisplatin/5-fluorouracil or cisplatin/capecitabine regimen.

Dose of ASLAN001 starts from 400mg BID; then, dose escalation to 500mg BID or dose de-escalation to 300mg BID will depend on DLTs observed in cohort.

Regimen A: Depends on preferred medical practice, Cohort 1A will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and 5 fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks; or will receive ASLAN001 400 mg BID in combination with Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks.

Regimen B: Cohort 1B will receive ASLAN001 400 mg BID in combination with cisplatin 80 mg/m2 IV infusion and oral capecitabine 1,000 mg/m2 BID for 14 days every 3 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients 20 years of age or older at the time written informed consent is obtained.

  2. Regimen A: Patients with metastatic solid tumors eligible for treatment with cisplatin and 5-fluorouracil. The standard dose and schedule of cisplatin and 5-fluorouracil will be according to the preference of investigators and institutions.

    Regimen B: Patients with metastatic solid tumors eligible for treatment with cisplatin in combination with capecitabine.

  3. Patients with a partial gastrectomy may be allowed to participate in the study as long as they can take oral medications and meet all other inclusion/exclusion criteria.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to enrolment:

Hematological function, as follows:

  • Absolute neutrophil count ≥ 1.5 x 109/L.
  • Platelet count ≥ 100 x 109/L.
  • Hemoglobin ≥ 9 g/dL.

Coagulation function, as follows:

  • Partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
  • International normalized ratio ≤ 1.5.

Renal function, as follows:

• Creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault formula.

Hepatic function, as follows:

  • Total bilirubin ≤ 1.5 x ULN.
  • AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present).

Exclusion Criteria:

  1. Patients with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy.
  2. Patients receiving proton pump inhibitors or H2 antagonists for established, symptomatic gastro duodenal ulceration or gastroesophageal reflux disease.
  3. Patients with unresolved toxicities of grade 2 or more from prior anti-cancer therapies.
  4. Untreated or symptomatic central nervous system metastases. Patients with a history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the patient is clinically stable and is off corticosteroids for at least 2 weeks prior to enrolment.
  5. Major surgical procedures within 28 days prior to enrolment.
  6. Clinically significant cardiovascular diseases that are symptomatic or uncontrolled.
  7. Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
  8. Pregnant or breast-feeding females.
  9. Patients who have hearing impairment, due to the potential for ototoxicity of cisplatin.
  10. Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease or any other condition which in the opinion of the Investigator could jeopardize the safety of the patient or the validity of the study results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Regimen A / Amended Regimen A

Regimen A: Cisplatin + 5-fluorouracil

ASLAN001 daily in combination with:

Cisplatin 80 mg/m2 IV infusion for 1 day and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks for up to 6 cycles.

Or

Amended Regimen A: Cisplatin + 5-fluorouracil + leucovorin

ASLAN001 daily in combination with:

Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks for up to 6 cycles.
Drug: ASLAN001
ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Other Names:
  • Varlitinib
  • ARRY-334543
Drug: cisplatin + 5-fluorouracil (or+ Leucovorin)

Cisplatin 80 mg/m2 IV infusion and 5-fluorouracil 800 mg/m2/day IV infusion for 5 days every 3 weeks;

Or

Cisplatin 35 mg/m2 24-hour infusion for day 1 and day 8, 5-fluorouracil 2,000 mg/m2 and Leucovorin 300mg/m2 24-hour infusion for day 1, day 8 and day 15 every 4 weeks.
Experimental: Regimen B

Regimen B: Cisplatin + capecitabine

ASLAN001 daily in combination with:

Cisplatin 60-80 mg/m2 IV infusion on Day 1 and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks for up to 6 cycles.
Drug: ASLAN001
ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Other Names:
  • Varlitinib
  • ARRY-334543
Drug: cisplatin + capecitabine
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of ASALN001
Time Frame: First 2 cycles

Safety and tolerability as evaluated with:

DLTs (in first 2 cycles); Maximum tolerated dose (MTD) of ASLAN001 in combination with cisplatin/capecitabine or cisplatin/5-FU will be determined.
First 2 cycles
Safety and Tolerability of ASALN001
Time Frame: Baseline to post-dose

Safety and tolerability as evaluated with:

Adverse events.
Baseline to post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Preliminary assessment of the efficacy
Time Frame: Along the study duration
•To provide a preliminary assessment of the efficacy of ASLAN001 when given in combination in Regimen A or Regimen B as measured by the objective response rate (ORR).
Along the study duration
Pharmacokinetics profile (AUC) of ASLAN001
Time Frame: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 6 hours (AUC0-6).
Along the study duration
Pharmacokinetics profile (Cmax) of ASLAN001
Time Frame: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax).
Along the study duration
Pharmacokinetics profile (Cmin) of ASLAN001
Time Frame: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to minimum (trough) plasma concentration (Cmin).
Along the study duration
Pharmacokinetics profile (RacAUC0-6) of ASLAN001
Time Frame: Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B.
To evaluate the pharmacokinetics of ASLAN001, when given in combination with Regimen A or Regimen B. Pharmacokinetic parameters including, but not limited to accumulation ratio for AUC (RacAUC0-6).
Pharmacokinetic measurements will be from Cycle 1 Day 1 to Cycle 3 Day 1 (each cycle is 28 days for Amended Regimen A, and 21 days for Regimen A and B.
Pharmacokinetics profile (Tmax) of ASLAN001
Time Frame: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with
Along the study duration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ASLAN Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: ASLAN Pharma, ASLAN Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 5, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 12, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 15, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 7, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 25, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ASLAN001-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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