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Trastuzumab and Vinorelbine in Advanced Breast Cancer

This study has been terminated.
(Not enough confirmed responses to continue treatment.)
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Genentech, Inc.
Information provided by (Responsible Party):
Ian E. Krop, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01185509
First received: August 18, 2010
Last updated: April 17, 2017
Last verified: April 2017
  Purpose
The purpose of this research study is to see what effects trastuzumab in combination with vinorelbine has on breast cancer when the participant has circulating tumor cells that are positive for the protein called HER2. Trastuzumab is an FDA approved drug that targets HER2. The drug combination of trastuzumab and vinorelbine is an effective treatment for patients with breast cancers that are positive for HER2. This trial seeks to determine if the combination can also benefit participants whose original breast cancer was HER2 negative but whose circulating tumor cells are HER2 positive.

Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
Drug: trastuzumab
Drug: vinorelbine
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
The analysis was performed for 2 separate cohorts due to a change in study conduct during the trial (see arm description).
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2 Negative Primary Tumors and HER2 Positive Circulating Tumor Cells

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67). ]
    ORR was defined as the percentage of patients achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.


Secondary Outcome Measures:
  • Clinical Benefit Rate (CBR) [ Time Frame: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67). ]
    CBR was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. SD needed to be a minimum 24 weeks in duration

  • Progression-Free Survival (PFS) [ Time Frame: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks and within 2 wks off-study; Median follow-up was 2.7 months. ]
    PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

  • Circulating Tumor Cells (CTCs) [ Time Frame: Assessed at baseline ]
    CTCs levels were determined based on established methods.

  • Circulating Tumor Cells (CTCs) [ Time Frame: Assessed at 6 weeks ]
    CTCs levels were determined based on established methods.

  • Circulating Tumor Cells (CTCs) [ Time Frame: Assessed when patient comes off-study ]
    CTCs levels were determined based on established methods.


Enrollment: 31
Actual Study Start Date: November 2010
Estimated Study Completion Date: September 2017
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab and Vinorelbine - Cohort A
Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.
Drug: trastuzumab Drug: vinorelbine
Other Name: navelbine
Experimental: Trastuzumab and Vinorelbine - Main Cohort
Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity. Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0). The CTC tests of the first 11 patients were done at DFCI. The study team then decided to proceed with a different CTC test performed outside of DFCI. Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.
Drug: trastuzumab Drug: vinorelbine
Other Name: navelbine

Detailed Description:

OBJECTIVES:

Primary

  • To assess the objective response rate (ORR) of trastuzumab and vinorelbine in patients with metastatic breast cancer with HER2 negative primary tumors and HER2 positive circulating tumor cells.

Secondary

  • To describe the number of CTCs and the CTCs characteristics before and after therapy, and to explore the correlation of these findings with response.
  • To further characterize the safety and tolerability.
  • To evaluate progression-free survival.
  • To evaluate clinical benefit rate (CR+PR+SD>24 weeks).

Exploratory

  • To determine the clinical feasibility of high-throughput mutation profiling on circulating tumor cells (CTCs).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic invasive mammary carcinoma. The primary cancer must be HER2 negative by fluorescence in situ hybridization and/or immunohistochemistry.
  • Patients must have CTCs with HER2 amplification by FISH.
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater with conventional techniques of as 10mm or greater with spiral CT scan.
  • Study participants must have either archival primary tumor or metastatic tumor tissue available to allow analysis to confirm their HER2 status.
  • Patients must have received at least 1 prior chemotherapy regimen for metastatic breast cancer or evidence of disease progression within 6 months of completing adjuvant chemotherapy. Patients can receive any number of biological or hormonal regimens and remain eligible.
  • 18 years of age or older
  • Life expectancy of greater than 3 months
  • ECOG Performance Status of 0, 1 or 2
  • Normal organ and marrow function as outlined in the protocol
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria:

  • Participants must have recovered from all reversible toxicities related to prior therapy before beginning protocol treatment, and may not have any pre-existing treatment-related toxicities in excess of grade 2
  • Participants may not be receiving any other investigational agents while participating in this study
  • Participants may not have received trastuzumab or vinorelbine in the past
  • Participants receiving any medications or substances that are inhibitors of cytochrome P450 isoenzymes in the CYP3A subfamily are ineligible.
  • EKG abnormalities of known clinical significance, such as prolonged QT.
  • Left ventricular ejection fraction < 50%
  • Patients with peripheral neuropathy of any etiology that exceeds grade 1 are ineligible
  • Uncontrolled intercurrent illness
  • Individuals with symptomatic or progressive brain metastases are ineligible. Subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for 1 month or longer after completion of local therapy. Any corticosteroid use for brain metastases must have been discontinued without subsequent appearance of symptoms for more than 4 weeks prior to study treatment.
  • Individuals with active second malignancy are ineligible. Patients that are disease-free from a previously treated non-breast malignancy and have a 20% or less chance of recurrence are eligible.
  • Pregnant or breast feeding women
  • HIV-positive individuals on combination antiretroviral therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185509

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Genentech, Inc.
Investigators
Principal Investigator: Ian Krop, MD, PhD Dana-Farber Cancer Institute
  More Information

Responsible Party: Ian E. Krop, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01185509     History of Changes
Other Study ID Numbers: 10-207
H4913s ( Other Identifier: Genentech, Inc )
Study First Received: August 18, 2010
Results First Received: April 17, 2017
Last Updated: April 17, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dana-Farber Cancer Institute:
HER2 negative
HER2 positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vinorelbine
Trastuzumab
Vinblastine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017