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

24 oktober 2018 uppdaterad av: 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.

Studieöversikt

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

31

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

20 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.

ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Andra namn:
  • Varlitinib
  • ARRY-334543

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.

Experimentell: 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.

ASLAN001 400mg BID daily; ASLAN001 500mg BID daily; or ASLAN001 300mg BID daily
Andra namn:
  • Varlitinib
  • ARRY-334543
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Safety and Tolerability of ASALN001
Tidsram: 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
Tidsram: Baseline to post-dose

Safety and tolerability as evaluated with:

Adverse events.

Baseline to post-dose

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Preliminary assessment of the efficacy
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with
Along the study duration

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Studiestol: ASLAN Pharma, ASLAN Pharmaceuticals

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

5 augusti 2014

Primärt slutförande (Faktisk)

12 juni 2017

Avslutad studie (Faktisk)

15 september 2017

Studieregistreringsdatum

Först inskickad

21 juni 2015

Först inskickad som uppfyllde QC-kriterierna

5 januari 2016

Första postat (Uppskatta)

7 januari 2016

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

25 oktober 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

24 oktober 2018

Senast verifierad

1 oktober 2018

Mer information

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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