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Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

Sponsor
Frederick R. Ueland, M.D. (Other)
Overall Status
Recruiting
CT.gov ID
NCT04608409
Collaborator
(none)
15
Enrollment
1
Location
4
Arms
55.4
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Lapatinib and Paclitaxel
 Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Dose-Escalation Study on the Safety of Lapatinib With Dose-Dense Paclitaxel in Patients With Platinum-Resistant Ovarian Cancer
Actual Study Start Date :
Nov 16, 2020
Anticipated Primary Completion Date :
Jun 30, 2025
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lapatinib - Group 1

Patients in this group will receive Lapatinib (500mg 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 (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 3

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 4

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.

Outcome Measures

Primary Outcome Measures

  1. Progression-free survival. [One year]

    Proportion of patients with progression-free survival at one year.

  2. Dose-limiting toxicity [4 weeks]

    Dose limiting toxicity (DLT) is calculated as the total number of patients experiencing DLTs divided by the total number treated.

Secondary Outcome Measures

  1. Change in plasma concentration of lapatinib. [15 days (on day 1, 8 and 15)]

    Plasma concentrations of lapatinib will be measured on days 1, 8 and 15.

Other Outcome Measures

  1. ABCB1 Expression [15 days (on day 1, 8 and 15)]

    Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 100 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Markey Cancer Center Lexington Kentucky United States 40536

Sponsors and Collaborators

  • Frederick R. Ueland, M.D.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Frederick R. Ueland, M.D., Professor, University of Kentucky
ClinicalTrials.gov Identifier:
NCT04608409
Other Study ID Numbers:
  • MCC-20-GYN-06
First Posted:
Oct 29, 2020
Last Update Posted:
Dec 8, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Keywords provided by Frederick R. Ueland, M.D., Professor, University of Kentucky
platinum-resistant
Additional relevant MeSH terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Paclitaxel
Lapatinib

Study Results

No Results Posted as of Dec 8, 2021