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Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer

6 november 2018 bijgewerkt door: Jennifer Specht, University of Washington

Combined Targeted Therapies for Triple Negative Advanced Breast Cancer - A Phase II Trial of Weekly Nab-Paclitaxel and Bevacizumab Followed by Maintenance Targeted Therapy With Bevacizumab and Erlotinib

This phase II trial studies how well giving paclitaxel albumin-stabilized nanoparticle (Nab-paclitaxel) formulation together with bevacizumab followed by bevacizumab and erlotinib hydrochloride work in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can prevent cancer growth by blocking the ability of cancer cells to grow and spread. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial evaluates a maintenance treatment with erlotinib and bevacizumab after Nab-paclitaxel and bevacizumab which may control cancer growth with biologic therapies.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

PRIMARY OBJECTIVES:

I. Progression free survival.

SECONDARY OBJECTIVES:

I. Response rate.

II. Overall survival.

III. Safety and toxicity.

IV. Exploratory biomarkers will be assessed as potential predictors of response to treatment including: expression of epidermal growth factor receptor (EGFR) and secreted protein acidic and rich in cysteine (SPARC) in the primary tumor and changes in levels of circulating tumor cells (CTCs) and circulating endothelial cells (CECs).

OUTLINE:

INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up per physician discretion.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

59

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Alaska
      • Anchorage, Alaska, Verenigde Staten, 99508
        • Anchorage Oncology Centre
      • Anchorage, Alaska, Verenigde Staten, 99508
        • Katmai Oncology Group
      • Anchorage, Alaska, Verenigde Staten, 99508
        • Providence Alaska Medical Center
    • Arizona
      • Yuma, Arizona, Verenigde Staten, 85364
        • Yuma Cancer Center
    • Idaho
      • Lewiston, Idaho, Verenigde Staten, 83501
        • Saint Joseph Regional Medical Center
    • Montana
      • Bozeman, Montana, Verenigde Staten, 59715
        • Bozeman Deaconess Hospital
      • Kalispell, Montana, Verenigde Staten, 59901
        • Kalispell Regional Medical Center
    • Oregon
      • Bend, Oregon, Verenigde Staten, 97701
        • Bend Memorial Clinic
    • Washington
      • Kennewick, Washington, Verenigde Staten, 99336
        • Kadlec Clinic Hematology and Oncology
      • Kirkland, Washington, Verenigde Staten, 98033
        • Evergreen Hospital Medical Center
      • Mount Vernon, Washington, Verenigde Staten, 98273
        • Skagit Valley Hospital Regional Cancer Care Center
      • Redmond, Washington, Verenigde Staten, 98052
        • Group Health Cooperative, Redmond
      • Seattle, Washington, Verenigde Staten, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
      • Sequim, Washington, Verenigde Staten, 98384
        • Olympic Medical Cancer Care Center
      • Spokane, Washington, Verenigde Staten, 99208
        • Spokane Valley Cancer Center-Mayfair
      • Tacoma, Washington, Verenigde Staten, 98405
        • Multicare Medical Oncology Hematology
      • Wenatchee, Washington, Verenigde Staten, 98801
        • Wenatchee Valley Medical Center

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Kind
  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

Inclusion Criteria:

  • Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
  • Be receiving first-line therapy for metastatic disease
  • Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration
  • OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL
  • Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment
  • Bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
  • Alkaline phosphatase =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
  • Platelets > 100,000 cells/mm^3
  • Hemoglobin > 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable
  • If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy
  • Pre-existing peripheral neuropathy, if present, must be < grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version 3.0)
  • Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines

Exclusion Criteria:

  • Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane
  • Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids
  • Pre-existing nephritic syndrome
  • Serious intercurrent medical or psychiatric illness including serious active infection
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to study enrollment
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, ulcer, or bone fracture

  • Proteinuria at screening as demonstrated by either:

    • Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR
    • Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is < 1.0 to be eligible; if the UPC ratio is >= 1.0 then the patient should undergo a 24-hour urine collection which must demonstrate =< 1 g of protein in 24 hours for the patient to be eligible)
  • Known hypersensitivity to any component of bevacizumab or to nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Tx (chemo, MoAb, and enzyme inhibitor)

INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity.
Biologisch: bevacizumab
IV gegeven
Andere namen:
  • Avastin
  • anti-VEGF gehumaniseerd monoklonaal antilichaam
  • anti-VEGF monoklonaal antilichaam
  • rhuMAb VEGF
Geneesmiddel: erlotinib hydrochloride
Gegeven PO
Andere namen:
  • OSI-774
  • erlotinib
  • CP-358.774
Geneesmiddel: paclitaxel albumine-gestabiliseerde formulering van nanodeeltjes
IV gegeven
Andere namen:
  • ABI-007
  • nab-paclitaxel
  • neem paclitaxel
  • nanoparticle albumine-gebonden paclitaxel

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Progression-free Survival (PFS)
Tijdsspanne: Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier survival curves will be used. A 95% confidence interval for the median PFS will be calculated. A lower bound greater than 8 months would be strong evidence that Nab-Paclitaxel- bevacizumab induction therapy followed by bevacizumab-erlotinib hydrochloride maintenance therapy is superior to paclitaxel and bevacizumab. However, a median PFS of 13 months or greater (regardless of whether the 95% confidence interval for the median extends below 8 months) could also indicate promising results.
Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Survival
Tijdsspanne: Time from date of registration to date of death due to any cause, assessed up to 8 years
Kaplan-Meier survival curves will be used.
Time from date of registration to date of death due to any cause, assessed up to 8 years
Percentage of Participants With Response
Tijdsspanne: Up to 8 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Up to 8 years
Incidence of Adverse Events as Assessed by National Cancer Institute CTCAE Version 3.0
Tijdsspanne: Up to 30 days after treatment discontinuation
Adverse events that meet severity grade 2 or greater will be collected and reported. The number and percent of subjects reporting adverse events (all, severe or worse, serious and related) will be summarized for all patients, and stratified by center and other subgroups of interest.
Up to 30 days after treatment discontinuation
EGFR and SPARC Expression in the Primary Tumor
Tijdsspanne: Up to 8 years
Up to 8 years
Changes in Levels of Circulating Tumor Cells
Tijdsspanne: Baseline to up to 8 years
Descriptive statistics, such as mean, standard deviation, and range, will be summarized for circulating tumor cells at baseline and last visit.
Baseline to up to 8 years
Changes in Levels of Circulating Endothelial Cells
Tijdsspanne: Baseline to up to 8 years
Descriptive statistics, such as mean and standard deviation, will be summarized for circulating endothelial cells at baseline and last visit.
Baseline to up to 8 years

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University of Washington

Medewerkers

National Cancer Institute (NCI)

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

23 april 2008

Primaire voltooiing (Werkelijk)

5 juli 2017

Studie voltooiing (Werkelijk)

28 september 2017

Studieregistratiedata

Eerst ingediend

12 augustus 2008

Eerst ingediend dat voldeed aan de QC-criteria

12 augustus 2008

Eerst geplaatst (Schatting)

13 augustus 2008

Updates van studierecords

Laatste update geplaatst (Werkelijk)

4 december 2018

Laatste update ingediend die voldeed aan QC-criteria

6 november 2018

Laatst geverifieerd

1 november 2018

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 6628 (Fred Hutchinson Cancer Research Center/UW Consortium)
  • P30CA015704 (Subsidie/contract van de Amerikaanse NIH)
  • NCI-2010-00041 (Register-ID: CTRP (Clinical Trial Reporting Program))

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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