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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02648425
• Other study ID #: ASLAN001-002
• Status: Completed
• Phase: Phase 1
• Start date: August 5, 2014
• Est. completion date: September 15, 2017

Study information

• Verified date: October 2018
• Source: Aslan Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 15, 2017
• Est. primary completion date: June 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• ASLAN001
ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
• cisplatin + capecitabine
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks
• 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.

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Aslan Pharmaceuticals

Countries where clinical trial is conducted

Hong Kong,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of ASALN001	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
Primary	Safety and Tolerability of ASALN001	Safety and tolerability as evaluated with: Adverse events.	Baseline to post-dose
Secondary	Preliminary assessment of the efficacy	•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
Secondary	Pharmacokinetics profile (AUC) of ASLAN001	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
Secondary	Pharmacokinetics profile (Cmax) of ASLAN001	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
Secondary	Pharmacokinetics profile (Cmin) of ASLAN001	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
Secondary	Pharmacokinetics profile (RacAUC0-6) of ASLAN001	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.
Secondary	Pharmacokinetics profile (Tmax) of ASLAN001	To evaluate the pharmacokinetics of ASLAN001, when given in combination with	Along the study duration