Back to resultsDose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer
Primary Purpose
Ovarian Cancer
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lapatinib and Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring platinum-resistant
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
Sites / Locations
- Markey Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Lapatinib - Group 1
Lapatinib - Group 2
Lapatinib - Group 3
Lapatinib - Group 4
Arm Description
Patients in this group will receive Lapatinib (500mg PO BID) and Paclitaxel (80mg/m2).
Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).
Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).
Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).
Outcomes
Primary Outcome Measures
Progression-free survival.
Proportion of patients with progression-free survival at one year.
Dose-limiting toxicity
Dose limiting toxicity (DLT) is calculated as the total number of patients experiencing DLTs divided by the total number treated.
Secondary Outcome Measures
Change in plasma concentration of lapatinib.
Plasma concentrations of lapatinib will be measured on days 1, 8 and 15.
Full Information
NCT ID
NCT04608409
First Posted
October 22, 2020
Last Updated
February 28, 2023
Sponsor
Frederick R. Ueland, M.D.
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04608409
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 17, 2021 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Frederick R. Ueland, M.D.
Collaborators
National Cancer Institute (NCI)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
platinum-resistant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lapatinib - Group 1
Arm Type
Experimental
Arm Description
Patients in this group will receive Lapatinib (500mg PO BID) and Paclitaxel (80mg/m2).
Arm Title
Lapatinib - Group 2
Arm Type
Experimental
Arm Description
Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).
Arm Title
Lapatinib - Group 3
Arm Type
Experimental
Arm Description
Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).
Arm Title
Lapatinib - Group 4
Arm Type
Experimental
Arm Description
Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).
Intervention Type
Drug
Intervention Name(s)
Lapatinib and Paclitaxel
Intervention Description
Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment.
Primary Outcome Measure Information:
Title
Progression-free survival.
Description
Proportion of patients with progression-free survival at one year.
Time Frame
One year
Title
Dose-limiting toxicity
Description
Dose limiting toxicity (DLT) is calculated as the total number of patients experiencing DLTs divided by the total number treated.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Change in plasma concentration of lapatinib.
Description
Plasma concentrations of lapatinib will be measured on days 1, 8 and 15.
Time Frame
15 days (on day 1, 8 and 15)
Other Pre-specified Outcome Measures:
Title
ABCB1 Expression
Description
Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing.
Time Frame
15 days (on day 1, 8 and 15)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frederick Ueland, MD
Phone
859-257-4550
Email
fuela0@uky.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frederick Ueland, MD
Organizational Affiliation
Markey Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer
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