Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

June 17, 2025 updated by: Frederick R. Ueland, M.D.

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Markey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lapatinib - Group 1
Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).
Drug: Lapatinib and Paclitaxel
Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment.
Experimental: Lapatinib - Group 2
Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).
Drug: Lapatinib and Paclitaxel
Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment.
Experimental: Lapatinib - Group 3
Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).
Drug: Lapatinib and Paclitaxel
Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival.
Time Frame: One year
Number of patients with progression-free survival at one year.
One year
Number of Participants With 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.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Plasma Concentration of Lapatinib Cycle 1
Time Frame: 15 days (on day 8 and 15)
Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration
15 days (on day 8 and 15)
Change in Plasma Concentration of Lapatinib Cycle 2
Time Frame: 15 days (on day 8 and 15)
Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration
15 days (on day 8 and 15)
Change in Plasma Concentration of Lapatinib Cycle 3
Time Frame: 15 days (on day 8 and 15)
Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration
15 days (on day 8 and 15)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
15 days (on day 1, 8 and 15)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Frederick R. Ueland, M.D.

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Frederick Ueland, MD, Markey Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2021

Primary Completion (Actual)

May 17, 2024

Study Completion (Actual)

May 17, 2024

Study Registration Dates

First Submitted

October 22, 2020

First Submitted That Met QC Criteria

October 28, 2020

First Posted (Actual)

October 29, 2020

Study Record Updates

Last Update Posted (Actual)

June 29, 2025

Last Update Submitted That Met QC Criteria

June 17, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-20-GYN-06
  • 5P30CA177558-10 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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