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Dose Escalation of Lapatinib With Paclitaxel in Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04608409
Recruitment Status : Not yet recruiting
First Posted : October 29, 2020
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
Frederick R. Ueland, M.D., University of Kentucky

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
Ovarian Cancer 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025


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.




Primary Outcome Measures :
  1. Progression-free survival. [ Time Frame: One year ]
    Proportion of patients with progression-free survival at one year.

  2. 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.


Secondary Outcome Measures :
  1. Change in plasma concentration of lapatinib. [ Time Frame: 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 [ Time Frame: 15 days (on day 1, 8 and 15) ]
    Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04608409


Contacts
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Contact: Frederick Ueland, MD 859-257-4550 fuela0@uky.edu

Locations
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United States, Kentucky
Markey Cancer Center
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Frederick R. Ueland, M.D.
Investigators
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Principal Investigator: Frederick Ueland, MD Markey Cancer Center
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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: October 29, 2020    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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., University of Kentucky:
platinum-resistant
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Lapatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors