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Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT04608409
Recruitment Status : Recruiting
First Posted : October 29, 2020
Last Update Posted : December 8, 2020
Sponsor:
Information provided by (Responsible Party):
Frederick R. Ueland, M.D., University of Kentucky

Tracking Information
First Submitted Date  ICMJE October 22, 2020
First Posted Date  ICMJE October 29, 2020
Last Update Posted Date December 8, 2020
Actual Study Start Date  ICMJE November 16, 2020
Estimated Primary Completion Date June 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
  • Progression-free survival. [ Time Frame: One year ]
    Proportion of patients with progression-free survival at one year.
  • Dose-limiting toxicity [ Time Frame: 4 weeks ]
    Dose limiting toxicity (DLT) is calculated as the total number of patients experiencing DLTs divided by the total number treated.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
Change in plasma concentration of lapatinib. [ Time Frame: 15 days (on day 1, 8 and 15) ]
Plasma concentrations of lapatinib will be measured on days 1, 8 and 15.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 28, 2020)
ABCB1 Expression [ Time Frame: 15 days (on day 1, 8 and 15) ]
Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer
Official Title  ICMJE A Phase I Dose-Escalation Study on the Safety of Lapatinib With Dose-Dense Paclitaxel in Patients With Platinum-Resistant Ovarian Cancer
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE Drug: Lapatinib and Paclitaxel
Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment.
Study Arms  ICMJE
  • Experimental: Lapatinib - Group 1
    Patients in this group will receive Lapatinib (500mg PO BID) and Paclitaxel (80mg/m2).
    Intervention: Drug: Lapatinib and Paclitaxel
  • Experimental: Lapatinib - Group 2
    Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).
    Intervention: Drug: Lapatinib and Paclitaxel
  • Experimental: Lapatinib - Group 3
    Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).
    Intervention: Drug: Lapatinib and Paclitaxel
  • Experimental: Lapatinib - Group 4
    Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).
    Intervention: Drug: Lapatinib and Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 28, 2020)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2025
Estimated Primary Completion Date June 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Frederick Ueland, MD 859-257-4550 fuela0@uky.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04608409
Other Study ID Numbers  ICMJE MCC-20-GYN-06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Frederick R. Ueland, M.D., University of Kentucky
Study Sponsor  ICMJE Frederick R. Ueland, M.D.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Frederick Ueland, MD Markey Cancer Center
PRS Account University of Kentucky
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP