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

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ClinicalTrials.gov Identifier: NCT02435927
Recruitment Status : Recruiting
First Posted : May 6, 2015
Last Update Posted : September 14, 2018
Sponsor:
Collaborators:
Aslan Pharmaceuticals
National Medical Research Council (NMRC), Singapore
Information provided by (Responsible Party):
National Cancer Centre, Singapore

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: ASLAN001+ CAPOX (Oxaliplatin, capecitabine) Drug: ASLAN001 + mFolfox6 (5-FU, leucovorin) Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 2014
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ASLAN001 + CAPOX
ASLAN001 + 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
Drug: ASLAN001+ CAPOX (Oxaliplatin, capecitabine)
ASLAN001 in combination with oxaliplatin and capecitabine
Other Name: eloxatin, xeloda

Experimental: ASLAN001 + mFolfox6
ASLAN001 + 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
Drug: ASLAN001 + mFolfox6 (5-FU, leucovorin)
ASLAN001 in combination with 5-FU and leucovorin
Other Name: 5-Fluorouracil, Folinic acid




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Pharmacokinetic parameter Maximum plasma concentration (Cmax) [ Time Frame: Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3 ]
  3. Pharmacokinetic parameter Minimum (trough) plasma concentration (Cmin) [ Time Frame: Day 1 and Day 15 of Cycle 1 and Day 1 of Cycle 3 ]
  4. Efficacy of ASLAN001 when given in combination in CAPOX or mFolfox6 as measured by the objective response rate (ORR) [ Time Frame: one year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02435927


Contacts
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Contact: Matthew CH Ng, Dr 64368000 matthew.ng.c.h@nccs.com.sg

Locations
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Singapore
National Cancer Centre Recruiting
Singapore, Singapore, 169610
Sponsors and Collaborators
National Cancer Centre, Singapore
Aslan Pharmaceuticals
National Medical Research Council (NMRC), Singapore
Investigators
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Principal Investigator: Matthew CH Ng National Cancer Centre, Singapore

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Responsible Party: National Cancer Centre, Singapore
ClinicalTrials.gov Identifier: NCT02435927     History of Changes
Other Study ID Numbers: ASLAN001-002SG
First Posted: May 6, 2015    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Additional relevant MeSH terms:
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Capecitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents