Clinical trial NCT04608409: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: platinum-resistant
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-10-29
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free survival.
timeFrame: One year
measure: Dose-limiting toxicity
timeFrame: 4 weeks
Secondary outcomes:
measure: Change in plasma concentration of lapatinib.
timeFrame: 15 days (on day 1, 8 and 15)
Other outcomes:
measure: ABCB1 Expression
timeFrame: 15 days (on day 1, 8 and 15)
Locations:
city: Lexington
country: United States
facility: Markey Cancer Center
state: Kentucky
Study officials:
affiliation: Markey Cancer Center
name: Frederick Ueland, MD
role: PRINCIPAL_INVESTIGATOR
References: