Clinical Trials /

Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

NCT04608409

Description:

This trial will be a phase I dose-escalation study of lapatinib and paclitaxel for platinum-resistant ovarian cancer, which will establish the phase II dose for subsequent efficacy trials.

Related Conditions:
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04608409

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer
  • Official Title: A Phase I Dose-Escalation Study on the Safety of Lapatinib With Dose-Dense Paclitaxel in Patients With Platinum-Resistant Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: MCC-20-GYN-06
  • NCT ID: NCT04608409

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
Lapatinib and PaclitaxelLapatinib - Group 1

Purpose

This trial will be a phase I dose-escalation study of lapatinib and paclitaxel for platinum-resistant ovarian cancer, which will establish the phase II dose for subsequent efficacy trials.

Detailed Description

      While ABCB1 (P-glycoprotein 1) upregulation after paclitaxel administration is well known,
      there is currently no clinically available method for preventing or overcoming it. To develop
      a therapy able to prevent ABCB1 upregulation and paclitaxel resistance, several ABCB1
      inhibitors have been evaluated in combination with paclitaxel in preclinical model systems.
      Pulsed-dose lapatinib and paclitaxel are synergistic and inhibition of ABCB1 by lapatinib
      increases sensitivity to paclitaxel. Lapatinib is FDA approved, orally available, and
      previously studied in combination with weekly paclitaxel for breast cancer at doses of 1000mg
      to 1250mg daily (7000-8250mg per week). This trial will use twice-daily dosing of lapatinib
      at a starting dose of 750 mg for 2 days (1500mg a day and 3000mg weekly dose), which is less
      than half of the continuous dose and has been shown to achieve plasma concentrations at 48
      hours that are associated with synergy. Therefore, these findings can be translated into a
      novel, well-tolerated, and convenient combination regimen with significant potential for
      clinical activity. This trial will be a phase I dose-escalation study of lapatinib and
      paclitaxel for platinum-resistant ovarian cancer, which will establish the phase II dose for
      subsequent efficacy trials.

Trial Arms

NameTypeDescriptionInterventions
Lapatinib - Group 1ExperimentalPatients in this group will receive Lapatinib (500mg PO BID) and Paclitaxel (80mg/m2).
  • Lapatinib and Paclitaxel
Lapatinib - Group 2ExperimentalPatients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).
  • Lapatinib and Paclitaxel
Lapatinib - Group 3ExperimentalPatients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).
  • Lapatinib and Paclitaxel
Lapatinib - Group 4ExperimentalPatients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).
  • Lapatinib and Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  histologically or cytologically confirmed ovarian cancer who recur within 12 months of
             platinum-based chemotherapy

          -  ECOG performance status less than or equal to 2

          -  Adequate organ and marrow function at baseline

          -  ability to sign a written informed consent document

        Exclusion Criteria:

          -  hypersensitivity to lapatinib or paclitaxel

          -  uncontrolled intercurrent illness

          -  receiving medications that inhibit or induce CYP3A4

          -  malabsorption syndrome

          -  congestive heart failure

          -  receiving any other anti-cancer investigational agents

          -  baseline neuropathy greater than Grade 1
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival.
Time Frame:One year
Safety Issue:
Description:Proportion of patients with progression-free survival at one year.

Secondary Outcome Measures

Measure:Change in plasma concentration of lapatinib.
Time Frame:15 days (on day 1, 8 and 15)
Safety Issue:
Description:Plasma concentrations of lapatinib will be measured on days 1, 8 and 15.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Frederick R. Ueland, M.D.

Trial Keywords

  • platinum-resistant

Last Updated

December 8, 2020