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

24 oktober 2018 bijgewerkt door: 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.

Studie Overzicht

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

31

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

20 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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
Andere namen:
  • 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.

Experimenteel: 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
Andere namen:
  • Varlitinib
  • ARRY-334543
Cisplatin 80 mg/m2 IV infusion and capecitabine 1,000 mg/m2 orally BID for 14 days every 3 weeks

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Safety and Tolerability of ASALN001
Tijdsspanne: 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
Tijdsspanne: Baseline to post-dose

Safety and tolerability as evaluated with:

Adverse events.

Baseline to post-dose

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Preliminary assessment of the efficacy
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: Along the study duration
To evaluate the pharmacokinetics of ASLAN001, when given in combination with
Along the study duration

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Studie stoel: ASLAN Pharma, ASLAN Pharmaceuticals

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

5 augustus 2014

Primaire voltooiing (Werkelijk)

12 juni 2017

Studie voltooiing (Werkelijk)

15 september 2017

Studieregistratiedata

Eerst ingediend

21 juni 2015

Eerst ingediend dat voldeed aan de QC-criteria

5 januari 2016

Eerst geplaatst (Schatting)

7 januari 2016

Updates van studierecords

Laatste update geplaatst (Werkelijk)

25 oktober 2018

Laatste update ingediend die voldeed aan QC-criteria

24 oktober 2018

Laatst geverifieerd

1 oktober 2018

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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