Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

Frederick R. Ueland, M.D.

Status and phase: Completed; Phase 1

Conditions: Ovarian Cancer

Treatments: Drug: Lapatinib and Paclitaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04608409

MCC-20-GYN-06

5P30CA177558-10 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: Female

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

Lapatinib - Group 1

Experimental group

Description:

Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).

Treatment:

Drug: Lapatinib and Paclitaxel

Lapatinib - Group 2

Experimental group

Description:

Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).

Treatment:

Drug: Lapatinib and Paclitaxel

Lapatinib - Group 3

Experimental group

Description:

Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).

Treatment:

Drug: Lapatinib and Paclitaxel