Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Vinorelbine

Paclitaxel

Albumin-Bound Paclitaxel

Lenograstim

Mitogens

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Adjuvants, Immunologic

Immunologic Factors

Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.

Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.

Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.

Weekly intravenous infusions over 30 minutes.

ABI-007

Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.

vinorelbine

Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered.

Trastuzumab is commercially available and was not supplied by the Sponsor.

During Part 1, participants followed a dosing regimen with ABI-007 and vinorelbine without G-CSF treatment. However, G-CSF was allowed for administration as necessary in accordance with commonly accepted clinical guidelines.

In Part 2, participants started G-CSF treatment in concurrence with their ABI-007 and vinorelbine treatments. G-CSF was administered to all participants on Days 2-7 of each cycle, at a dose of 5 mcg/kg. If the participant's absolute neutrophil (ANC) count was \>20,000/mm\^3 on the day of anticipated chemotherapy, the site staff reduced the daily dose of G-CSF by 50% to 2.5 mcg/kg.

G-CSF is commercially available and was not supplied by the Sponsor.

G-CSF

The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive disease may receive Herceptin, and 2) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the presence of planned growth factor support with G-CSF.

A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer

An Open-Label Phase I/II Study of Weekly ABI-007 and Vinorelbine With or Without G-CSF in Patients With Stage IV (Metastatic) Breast Cancer

Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation.

Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Any drug-related toxicities CTC Grade 3 or higher were considered dose limiting. Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death. Other conditions considered dose-limiting toxicities include:

* requirement of a dose adjustment during the first 4 weeks
* a dose delay of \>3 weeks during the first 4 weeks Grade 3 or greater toxicities attributed to the use of Herceptin were not considered dose-limiting toxicities.

The optimal tolerated dose of ABI-007 and vinorelbine given concurrently was defined as the dose administered in the absence of DLTs.

Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events.

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) blood counts were graded using NCI CTCAE version 3.

ANC:

Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 1.5\*10\^9/L; Grade 2 = \<1.5 - 1.0\*10\^9/L; Grade 3 = \<1.0 - 0.5\*10\^9/L; Grade 4 = \<0.5\*10\^9/L

WBC:

Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 3.0\*10\^9/L; Grade 2 = \<3.0 - 2.0\*10\^9/L; Grade 3 = \<2.0 - 1.0\*10\^9/L; Grade 4 = \<1.0\*10\^9/L

Platelets:

Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 75.0\*10\^9/L; Grade 2 = \<75.0 - 50.0\*10\^9/L; Grade 3 = \<50.0 - 25.0\*10\^9/L; Grade 4 = \<25.0\*10\^9/L

Hemoglobin:

Grade 0 = within normal limits; Grade 1 = \< lower limit of normal - 100 g/L ; Grade 2 = \<100 - 80 g/L; Grade 3 = \<80 - 65 g/L; Grade 4 = \<65 g/L

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.

Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). See Outcome #1 for definitions of CR and PR.

RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

Complete response (CR) and partial response (PR) are defined in outcome #1. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

Because no patients died as a result of a non-disease progression event, the analysis of PFS was identical to the analysis for TTP.

Participant survival is the time from the first dose of study drug to participant death from any cause. Participants that did not die were censored at the last known time the participant was alive.

Celgene

Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants from study Parts 1 and 2 are combined.

80 mg ABI-007 + 15 mg Vinorelbine

Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants are from study Part 2.

90 mg ABI-007 + 20 mg Vinorelbine

Part 1: 80 mg ABI-007 + 15 mg Vinorelbine

Part 2: 80 mg ABI-007 + 15 mg Vinorelbine

Part 2: 90 mg ABI-007 + 20 mg Vinorelbine

Total

< 65 years

>= 65 years

Age, Customized

Sex: Female, Male

Asian

White, Non-Hispanic and Non-Latino

White, Hispanic or Latino

Race/Ethnicity, Customized

Pre-menopausal

Post-menopausal

Menopausal Status

Never Smoked

Current Smoker

Previous Smoker, but have Stopped

Smoking Status

Status 0 (Asymptomatic)

Status 1 (Symptomatic but completely ambulatory)

Status 2 (Ambulatory but unable to work)

Status 3 (Limited self-care)

Status 4 (Completely disabled)

Status 5 (Death)

Eastern Cooperative Oncology Group (ECOG) Performance Status

Associate Director, Clinical Trials Disclosure

Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)

Participants With Dose Limiting Toxicities

At least 1 ABI-007 dose reduction

At least 1 Vinorelbine dose reduction

At least 1 ABI-007 dose interruption

At least 1 Vinorelbine dose interruption

At least 1 therapy delay

Percentage of Participants With Discontinued, Delayed or Interrupted Therapy

ANC: grade 0

ANC: grade 1

ANC: grade 2

ANC: grade 3

ANC: grade 4

WBC: grade 0

WBC: grade 1

WBC: grade 2

WBC: grade 3

WBC: grade 4

Platelets: grade 0

Platelets: grade 1

Platelets: grade 2

Platelets: grade 3

Platelets: grade 4

Hemoglobin: grade 0

Hemoglobin: grade 1

Hemoglobin: grade 2

Hemoglobin: grade 3

Hemoglobin: grade 4

Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)

Platelets

Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count

Nadir Measurement for Hemoglobin (Hgb)

Disease control

Complete response

Partial response

Stable disease >=16 weeks

Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)

Treated population of participants with disease progression

Kaplan Meier Estimate for Time to Disease Progression (TTP)

Kaplan-Meier Estimate for Duration of Response

Treated population of participants who had disease progression or who died

Kaplan Meier Estimate for Progression-Free Survival (PFS)

Kaplan-Meier Estimates for Participant Survival

Overall Study

Amino Acids

Fulvestrant

Neratinib

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

After the screening procedures confirm participation in the research study.

- Each Cycle = 28 days

* Neratinib (oral, once daily)
* Fulvestrant, injection, on 2 days for cycle 1, then one time per cycle thereafter

Neratinib will be given orally once daily on a continuous daily dosing schedule i.e., no break in dosing. Dosage per protocol

NERATINIB

Fulvestrant will be given via injection every two weeks for the first 28-day cycle and every four weeks thereafter, dosage per protocol

FULVESTRANT

Aditya Bardia, MD,MPH

This is a Phase 2 open label, multi-center non-randomized interventional study designed to evaluate the safety and efficacy of combining Neratinib plus Fulvestrant in previously treated metastatic HR-positive, HER2-negative breast cancer.

* This research study involves the study drug Neratinib
* The standard of care drug Fulvestrant

* The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

  * This research study involves the study drug Neratinib
  * The standard of care drug Fulvestrant
* It is expected that about 25 people will take part in this research study.
* This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
* The U.S. Food and Drug Administration (FDA) has not approved Neratinib for this specific disease but it has been approved for other uses.
* The FDA has approved Fulvestrant as a treatment option for this disease. Fulvestrant is a standard of care drug that will be administered.

Fulvestrant + Neratinib In Breast Cancer

An Open-Label Phase II Trial of Fulvestrant And Neratinib in Previously Treated HRPositive, HER2-Negative Metastatic Breast Cancer Subjects Assessed With a Test Measuring Live Cell HER2 Signaling Function

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

ORR is defined as the proportion of patients with a confirmed CR or PR per Investigator's assessment per RECIST v1.1

defined for patients with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response

defined as the cumulative proportion of patients with an objective response (CR or PR) after study treatment. The cumulative number of patients with an OR will be determined at the end of each time period and the cumulative incidence will then be calculated.

is defined for patients with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. DR will be analyzed using Kaplan-Meier methods and descriptive statistics.

defined as the time from the first dose of study treatment to the date of progression by RECIST v1.1 or death due to any cause, whichever occurs first. PFS will be analyzed using Kaplan-Meier methods and descriptive statistics.

defined as the time from the first dose of study treatment to the date of death. OS will be analyzed using Kaplan-Meier methods and descriptive statistics.

NCI CTCAE (version 5.0) criteria for adverse events

The correlation between quantitative CELsignia score and OR, will be assessed to evaluate different cut-off values and corresponding treatment responses. CELsignia HER2 Pathway Activity Test

The correlation between quantitative CELsignia score and CB, will be assessed to evaluate different cut-off values and corresponding treatment responses. (CELsignia HER2 Pathway Activity Test)

The correlation between quantitative CELsignia score and PFS, will be assessed to evaluate different cut-off values and corresponding treatment responses. (CELsignia HER2 Pathway Activity Test)

The correlation between quantitative CELsignia score and molecular alterations in plasma, particularly HER2 mutations. ( CELsignia HER2 Pathway Activity Test)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer	NCT00140140	Stage IV (Metas...	ABI-007 vinorelbine Trastuzumab G-CSF	18 Years -	Celgene
A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer	NCT00140140	Stage IV (Metas...	ABI-007 vinorelbine Trastuzumab G-CSF	18 Years -	Celgene
Fulvestrant + Neratinib In Breast Cancer	NCT04901299	Stage IV (Metas... Metastatic Brea... ER Positive Bre... PR-Positive Bre... HER2-negative B... Invasive Breast...	NERATINIB FULVESTRANT	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for stage iv (metastatic) breast cancer