Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients With Prior Taxane Treatment, A ComboMATCH Treatment Trial

NCT ID: NCT05554341

Last Updated: 2025-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-14

Study Completion Date

2026-06-30

Brief Summary

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This phase II ComboMATCH treatment trial evaluates nilotinib with paclitaxel for the treatment of patients with solid cancers that are growing, spreading, or getting worse (progressive) and that have previously been treated with taxane therapies. Nilotinib is in a class of medications called kinase inhibitors. It works by binding to and blocking the action of a protein called ABL, which signals tumor cells to multiply. This helps slow or stop the proliferation of tumor cells. Paclitaxel is a drug that blocks cell growth by stopping cell division and it may kill tumor cells. Giving nilotinib with paclitaxel may be effective at treating patients with progressive solid cancers that have previously been treated with taxane therapies.

Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with taxane-refractory advanced malignancies who have objective responses (OR) to treatment with nilotinib hydrochloride monohydrate (nilotinib) and paclitaxel.

SECONDARY OBJECTIVE:

I. Collect tissue and provide it to the ComboMATCH registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH registration protocol.

EXPLORATORY OBJECTIVES:

I. To evaluate progression free survival (PFS) at 6 months on study agents. II. To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens and cell-free deoxyribonucleic acid (DNA).

OUTLINE:

Patients receive nilotinib hydrochloride monohydrate orally (PO) twice daily (BID) on days 1-28 and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Patients also undergo collection of blood samples and tumor biopsy on study.

After completion of study treatment, patients are followed until disease progression, and for survival for 3 years from registration.

Conditions

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Metastatic Malignant Solid Neoplasm Refractory Malignant Solid Neoplasm

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (nilotinib hydrochloride monohydrate, paclitaxel)

Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the study. Patients also undergo collection of blood samples and tumor biopsy on study.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Nilotinib Hydrochloride Monohydrate

Intervention Type DRUG

Given PO

Paclitaxel

Intervention Type DRUG

Given IV

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Nilotinib Hydrochloride Monohydrate

Given PO

Intervention Type DRUG

Paclitaxel

Given IV

Intervention Type DRUG

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI AMN 107 AMN-107 AMN107 Nilotinib Monohydrochloride Monohydrate Tasigna Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat

Eligibility Criteria

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Inclusion Criteria

* Patient must be enrolled on the ComboMATCH registration protocol (EAY191) at the time of registration to the EAY191-E4 study
* Patient must be \>= 18 years of age
* Patient must not have any of the following mutations (as determined by the ComboMATCH registration protocol), which are known to confer sensitivity or resistance to nilotinib monotherapy:

* KIT: W557R, V559D, V559A, L576P, and K642E
* PDGFR-alpha: D842V
* Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH registration trial (EAY191)

* NOTE: The current actionable mutation of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website
* NOTE: Novel/dynamic aMOI can be submitted for review per the process described in the ComboMATCH registration protocol
* Patient must be willing to provide blood samples for research purposes
* Patient must have had at least one prior line of therapy in the metastatic setting
* Patient must have previously undergone taxane therapy (in the metastatic setting)

* Patients who previously responded to prior taxane therapy must have received their last dose of taxane therapy within 6 months prior to EAY191-E4 registration and have had no other intervening treatment prior to EAY191-E4 registration
* Patients who did not respond to prior taxane therapy are eligible regardless of the time elapsed since the prior taxane therapy or any other intervening therapies
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Patient must not have had platinum-resistant epithelial serous ovarian cancer
* Patients must not have neuropathy \>= grade 2 within 14 days of registration/randomization
* Patient must have documented QT interval with Fridericia's correction (QTcF) of =\< 450 msec within 8 days prior to EAY191-E4 registration. Patients with a QTcF interval of \>= 450 msec at registration or patients with congenital long QT syndrome are not eligible
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

* All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 3 months after the last dose of study drug
* Patients must have progressive disease
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (with the exception of those with Gilbert syndrome, who must have total bilirubin =\< 3 x institutional ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 institutional upper limit of normal; \< 5.0 x ULN in patients with liver metastases
* Creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 mg/dL
* Patient must have the ability to swallow medications
* Patient must have completed any prior therapy ≥ 4 weeks or ≥ 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed ≥ 4 weeks prior to enrollment; prior palliative radiation should have been completed ≥ 2 weeks prior to enrollment. Patients must be ≥ 2 weeks since any investigational agent administered as part of a phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for ≥ 1 month after treatment of the brain metastases
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sarah Shin

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Kingman Regional Medical Center

Kingman, Arizona, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

Presbyterian Intercommunity Hospital

Whittier, California, United States

Site Status

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Site Status

Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho, United States

Site Status

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States

Site Status

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, United States

Site Status

Advocate Good Shepherd Hospital

Barrington, Illinois, United States

Site Status

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status

Centralia Oncology Clinic

Centralia, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States

Site Status

Advocate Illinois Masonic Medical Center

Chicago, Illinois, United States

Site Status

AMG Crystal Lake - Oncology

Crystal Lake, Illinois, United States

Site Status

Carle at The Riverfront

Danville, Illinois, United States

Site Status

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Illinois CancerCare-Dixon

Dixon, Illinois, United States

Site Status

Advocate Good Samaritan Hospital

Downers Grove, Illinois, United States

Site Status

Carle Physician Group-Effingham

Effingham, Illinois, United States

Site Status

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status

Advocate Sherman Hospital

Elgin, Illinois, United States

Site Status

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Site Status

Advocate South Suburban Hospital

Hazel Crest, Illinois, United States

Site Status

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status

AMG Libertyville - Oncology

Libertyville, Illinois, United States

Site Status

Condell Memorial Hospital

Libertyville, Illinois, United States

Site Status

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Site Status

Cancer Care Center of O'Fallon

O'Fallon, Illinois, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Site Status

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peru

Peru, Illinois, United States

Site Status

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Springfield Clinic

Springfield, Illinois, United States

Site Status

Springfield Memorial Hospital

Springfield, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Illinois CancerCare - Washington

Washington, Illinois, United States

Site Status

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Lafayette Family Cancer Center-EMMC

Brewer, Maine, United States

Site Status

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, United States

Site Status

Trinity Health Medical Center - Brighton

Brighton, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, United States

Site Status

Trinity Health Medical Center - Canton

Canton, Michigan, United States

Site Status

Chelsea Hospital

Chelsea, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, United States

Site Status

Cancer Hematology Centers - Flint

Flint, Michigan, United States

Site Status

Genesee Hematology Oncology PC

Flint, Michigan, United States

Site Status

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

University of Michigan Health - Sparrow Lansing

Lansing, Michigan, United States

Site Status

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, United States

Site Status

Henry Ford Saint John Hospital - Macomb Medical

Macomb, Michigan, United States

Site Status

Huron Gastroenterology PC

Ypsilanti, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, United States

Site Status

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, United States

Site Status

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status

Parkland Health Center - Farmington

Farmington, Missouri, United States

Site Status

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Missouri Baptist Sullivan Hospital

Sullivan, Missouri, United States

Site Status

BJC Outpatient Center at Sunset Hills

Sunset Hills, Missouri, United States

Site Status

Community Hospital of Anaconda

Anaconda, Montana, United States

Site Status

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Bozeman Health Deaconess Hospital

Bozeman, Montana, United States

Site Status

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status

Logan Health Medical Center

Kalispell, Montana, United States

Site Status

Community Medical Center

Missoula, Montana, United States

Site Status

OptumCare Cancer Care at Seven Hills

Henderson, Nevada, United States

Site Status

OptumCare Cancer Care at Charleston

Las Vegas, Nevada, United States

Site Status

OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Mount Sinai Hospital

New York, New York, United States

Site Status

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States

Site Status

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Site Status

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status

Dayton Physician LLC - Englewood

Dayton, Ohio, United States

Site Status

Kettering Medical Center

Kettering, Ohio, United States

Site Status

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Saint Alphonsus Cancer Care Center-Ontario

Ontario, Oregon, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Providence Saint Vincent Medical Center

Portland, Oregon, United States

Site Status

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Swedish Cancer Institute-Edmonds

Edmonds, Washington, United States

Site Status

Swedish Cancer Institute-Issaquah

Issaquah, Washington, United States

Site Status

Valley Medical Center

Renton, Washington, United States

Site Status

Swedish Medical Center-First Hill

Seattle, Washington, United States

Site Status

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

Site Status

ThedaCare Regional Cancer Center

Appleton, Wisconsin, United States

Site Status

Aurora Cancer Care-Grafton

Grafton, Wisconsin, United States

Site Status

Aurora BayCare Medical Center

Green Bay, Wisconsin, United States

Site Status

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Aurora Bay Area Medical Group-Marinette

Marinette, Wisconsin, United States

Site Status

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Aurora Sinai Medical Center

Milwaukee, Wisconsin, United States

Site Status

Vince Lombardi Cancer Clinic - Oshkosh

Oshkosh, Wisconsin, United States

Site Status

Vince Lombardi Cancer Clinic-Sheboygan

Sheboygan, Wisconsin, United States

Site Status

Aurora Medical Center in Summit

Summit, Wisconsin, United States

Site Status

Vince Lombardi Cancer Clinic-Two Rivers

Two Rivers, Wisconsin, United States

Site Status

Aurora Cancer Care-Milwaukee West

Wauwatosa, Wisconsin, United States

Site Status

Aurora West Allis Medical Center

West Allis, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2022-07264

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY191-E4

Identifier Type: OTHER

Identifier Source: secondary_id

EAY191-E4

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2022-07264

Identifier Type: -

Identifier Source: org_study_id

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