Clinical Trials /

ASLAN001 in Combination With Oxaliplatin and Capecitabine or Oxaliplatin and 5-FU With Leucovorin

NCT02435927

Description:

This is a Phase I, open-label, dose escalation study of ASLAN001 given in combination with CAPOX or mFolfox6, in patients with metastatic solid tumours, whom are suitable to receive CAPOX or mFolfox6, or with tumours that have dysregulated EGFR or HER2 signaling.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ASLAN001 in Combination With Oxaliplatin and Capecitabine or Oxaliplatin and 5-FU With Leucovorin
  • Official Title: Phase I Study to Evaluate the Safety and Tolerability of ASLAN001 in Combination With Oxaliplatin and Capecitabine or Oxaliplatin and 5-FU With Leucovorin

Clinical Trial IDs

  • ORG STUDY ID: ASLAN001-002SG
  • NCT ID: NCT02435927

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
ASLAN001+ CAPOX (Oxaliplatin, capecitabine)eloxatin, xelodaASLAN001 + CAPOX
ASLAN001 + mFolfox6 (5-FU, leucovorin)5-Fluorouracil, Folinic acidASLAN001 + mFolfox6

Purpose

This is a Phase I, open-label, dose escalation study of ASLAN001 given in combination with CAPOX or mFolfox6, in patients with metastatic solid tumours, whom are suitable to receive CAPOX or mFolfox6, or with tumours that have dysregulated EGFR or HER2 signaling.

Detailed Description

      The study will use standard 3+3 design to determine the MTD (maximum tolerated dose) of
      ASLAN001 in combination with fixed dose of Oxaliplatin/Capecitabine (CAPOX) or
      5-FU/leucovorin (mFolfox6).

      MTD of ASLAN001 in combination with CAPOX will first be determined followed by the
      combination with mFolfox6.

      The recommended Phase II dose will be the highest dose of the combination therapy that is
      considered to be tolerated in 6 patients.
    

Trial Arms

NameTypeDescriptionInterventions
ASLAN001 + CAPOXExperimentalASLAN001 + CAPOX: ASLAN001 twice daily in combination with oxaliplatin 130 mg/m2 intravenously on day 1 and capecitabine 850 mg/m2 orally twice daily on days 1 to 14 every 3 weeks
  • ASLAN001+ CAPOX (Oxaliplatin, capecitabine)
ASLAN001 + mFolfox6ExperimentalASLAN001 + mFolfox6: ASLAN001 twice daily in combination with mFolfox6 (oxaliplatin 85 mg/m2 intravenously on day 1 and 5-FU bolus 400mg/m2 i.v on day 1 and as a continuous infusion 2400mg/ m2 over 46h and leucovorin 400mg/2 i.v on day 1) every 2 weeks
  • ASLAN001 + mFolfox6 (5-FU, leucovorin)

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with metastatic solid tumours eligible for treatment with oxaliplatin in
             combination with capecitabine / 5-FU (fluorouracil) and leucovorin or who progressed
             following standard therapy or patients with EGFR (epidermal growth factor receptor )
             or HER2 dysregulated tumours.

          2. 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.

          3. Eastern Cooperative Oncology Group performance status of 0 or 1.

          4. 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: Prothrombin time and activated partial
             thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory
             normal range.

             • 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. Aspartate
             aminotransferase and alanine aminotransferase ≤ 2.5 x ULN (≤ 5 x ULN if liver
             metastases are present).

          5. Patients undergoing mandatory biopsy in dose expansion of a non-DLT cohort should have
             any of the following:

               -  known HER2 or EGFR dysregulation

               -  Patients with T790M mutation will be excluded.

               -  Co-expression of HER2 and EGFR

          6. Archival tumour sample is available for molecular profiling, unless undergoing tumour
             biopsy as part of the trial.

        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. H2
             antagonist can be prescribed after DLT (dose-limiting toxicity) period (the first 2
             cycles) at the discretion of the investigator.

          3. Patients with unresolved toxicities of grade 2 or more from prior anti-cancer
             therapies excluding alopecia.

          4. Untreated or symptomatic central nervous system metastases. Patients with treated
             brain metastases stable for 3 months are eligible to enroll.

          5. Major surgical procedures within 28 days prior to enrolment.

          6. Clinically significant cardiovascular diseases that are symptomatic or uncontrolled.

          7. Known active infection for human immunodeficiency virus, hepatitis B and C.

          8. Pregnant or breast-feeding females.

          9. Treatment with any of the following anti-cancer therapies prior to the first dose of
             study drugs within the stated timeframes

               -  Cyclical chemotherapy within a period of time that is shorter than the cycle
                  length used for that treatment. Exception for weekly chemotherapy regimens, where
                  a minimum of 2 week washout from the last dose is required.

               -  Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or
                  ≤ 4 weeks, whichever is shorter, prior to starting study drug

               -  Continuous or intermittent small molecule therapeutics within a period of time
                  that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug

               -  Any other investigational agents within a period of time that is ≤ 5 t1/2 or less
                  than the cycle length used for that treatment or ≤ 4 weeks (whichever is
                  shortest) prior to starting study drug

               -  Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2
                  weeks prior to starting study drug

               -  Previous combination therapy with xeloda and oxaliplatin within 6 months of study
                  treatment.

               -  Previous combination therapy with Oxaliplatin, 5-FU and Leucovorin (mFolfox6)
                  within 6 months of study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of ASLAN001 when used in combination with Oxaliplatin and Capecitabine (CAPOX) or Oxaliplatin and 5-FU with leucovorin (mFolfox6)
Time Frame:one year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic parameter Area under the plasma concentration time curve (AUC)
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3
Safety Issue:
Description:
Measure:Pharmacokinetic parameter Maximum plasma concentration (Cmax)
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3
Safety Issue:
Description:
Measure:Pharmacokinetic parameter Minimum (trough) plasma concentration (Cmin)
Time Frame:Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3
Safety Issue:
Description:
Measure:Efficacy of ASLAN001 when given in combination in CAPOX or mFolfox6 as measured by the objective response rate (ORR)
Time Frame:one year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Centre, Singapore

Last Updated

September 12, 2018