Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

Ovarian Cancer Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04608409
• Other study ID #: MCC-20-GYN-06
• Secondary ID: 5P30CA177558-10
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 17, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: February 2024
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Lapatinib and Paclitaxel
Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment.

Locations

Country	Name	City	State
United States	Markey Cancer Center	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Frederick R. Ueland, M.D.	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ABCB1 Expression	Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing.	15 days (on day 1, 8 and 15)
Primary	Progression-free survival.	Proportion of patients with progression-free survival at one year.	One year
Primary	Dose-limiting toxicity	Dose limiting toxicity (DLT) is calculated as the total number of patients experiencing DLTs divided by the total number treated.	4 weeks
Secondary	Change in plasma concentration of lapatinib.	Plasma concentrations of lapatinib will be measured on days 1, 8 and 15.	15 days (on day 1, 8 and 15)