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| ID | Type | Description | Link |
|---|---|---|---|
| 5P30CA177558-10 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lapatinib - Group 1 | Experimental | Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2). |
|
| Lapatinib - Group 2 | Experimental | Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2). |
|
| Lapatinib - Group 3 | Experimental | Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lapatinib and Paclitaxel | Drug | Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival. | Number of patients with progression-free survival at one year. | One year |
| Number of Participants With 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma Concentration of Lapatinib Cycle 1 | Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration | 15 days (on day 8 and 15) |
| Change in Plasma Concentration of Lapatinib Cycle 2 |
| Measure | Description | Time Frame |
|---|---|---|
| ABCB1 Expression | Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing. | 15 days (on day 1, 8 and 15) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frederick Ueland, MD | Markey Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Markey Cancer Center | Lexington | Kentucky | 40536 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41749879 | Derived | Cao CD, McCorkle JR, Yan D, Esfahani HS, Jayswal R, Piecoro D, Li N, Baldwin LA, Miller RW, Desimone CP, Dietrich CS, Ueland FR, Kolesar JM. A Phase 1 Dose Escalation of Lapatinib and Paclitaxel in Recurrent Ovarian Cancer. Cancers (Basel). 2026 Feb 14;18(4):626. doi: 10.3390/cancers18040626. |
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Sixteen patients were evaluable for efficacy, toxicity, and response.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lapatinib - Group 1 | Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| FG001 | Lapatinib - Group 2 | Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| FG002 | Lapatinib - Group 3 | Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lapatinib - Group 1 | Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| BG001 | Lapatinib - Group 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression-free Survival. | Number of patients with progression-free survival at one year. | Posted | Count of Participants | Participants | One year |
|
30 days after discontinuation (last dose) of lapatinib, up to 3 cycles (a cycle is 28 days)
If a participant experienced more than one adverse event within a toxicity category, the participant is counted once under that category. If a participant had more than one count for a particular toxicity, the participant was counted once for that toxicity.
CTCAE v5.0 was used for coding.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lapatinib - Group 1 | Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocyte count decreased | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Frederick Ueland | University of Kentucky | 859-257-1613 | frederick.ueland@uky.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Feb 1, 2023 | May 28, 2025 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
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| ID | Term |
|---|---|
| D000077341 | Lapatinib |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration
| 15 days (on day 8 and 15) |
| Change in Plasma Concentration of Lapatinib Cycle 3 | Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration | 15 days (on day 8 and 15) |
Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| BG002 | Lapatinib - Group 3 | Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Lapatinib - Group 3 | Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. |
|
|
| Primary | Number of Participants With Dose-limiting Toxicity | Dose limiting toxicity (DLT) is calculated as the total number of patients experiencing DLTs divided by the total number treated. | Posted | Count of Participants | Participants | 4 weeks |
|
|
|
| Secondary | Change in Plasma Concentration of Lapatinib Cycle 1 | Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration | Plasma lapatinib concentrations were analyzed among samples from patients who completed dosing for the assigned treatment arm and had blood drawn within 24 hours of the last lapatinib dose. | Posted | Mean | Standard Deviation | ng/ml | 15 days (on day 8 and 15) |
|
|
|
| Other Pre-specified | ABCB1 Expression | Levels of ABCB1 expression (cell-free RNA) will be measured using Nanostring sequencing. | Not Posted | 15 days (on day 1, 8 and 15) | Participants |
| Secondary | Change in Plasma Concentration of Lapatinib Cycle 2 | Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration | Plasma lapatinib concentrations were analyzed among samples from patients who completed dosing for the assigned treatment arm and had blood drawn within 24 hours of the last lapatinib dose. | Posted | Mean | Standard Deviation | ng/ml | 15 days (on day 8 and 15) |
|
|
|
| Secondary | Change in Plasma Concentration of Lapatinib Cycle 3 | Plasma concentrations of lapatinib will be measured on days 8 and 15 prior to paclitaxel administration | Plasma lapatinib concentrations were analyzed among samples from patients who completed dosing for the assigned treatment arm and had blood drawn within 24 hours of the last lapatinib dose. | Posted | Mean | Standard Deviation | ng/ml | 15 days (on day 8 and 15) |
|
|
|
| 3 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Lapatinib - Group 2 | Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. | 6 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Lapatinib - Group 3 | Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2). Lapatinib and Paclitaxel: Participants will receive twice-daily Lapatinib, beginning two days prior to Paclitaxel treatment. | 2 | 7 | 0 | 7 | 7 | 7 |
| Fever | General disorders | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Ventricular tachycardia | Cardiac disorders | Systematic Assessment |
|
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Creatinine increased | Investigations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Other | Investigations | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperphosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Edema limbs | General disorders | Systematic Assessment |
|
| Gait disturbance | General disorders | Systematic Assessment |
|
| Malaise | General disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Other | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle cramp | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Other | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Paroxysmal atrial tachycardia | Cardiac disorders | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
|
| Ventricular tachycardia | Cardiac disorders | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
|
| Papulopustular rash | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | Systematic Assessment |
|
| Other | Renal and urinary disorders | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
|
| Other | Reproductive system and breast disorders | Systematic Assessment |
|
| Vaginal pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Flushing | Vascular disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Other | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
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| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| Day 15 |
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| Day 15 |
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