Trastuzumab and Vinorelbine in Advanced Breast Cancer

NCT01185509 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 10-207H4913s
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Breast Cancer; Metastatic Breast Cancer

Keywords

HER2 negative; HER2 positive

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  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).

Secondary Outcomes (3)

• Clinical Benefit Rate (CBR)

  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).

• Progression-Free Survival (PFS)

  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.

• Baseline Level of Circulating Tumor Cells (CTCs)

  Assessed at baseline

Study Arms (2)

Trastuzumab and Vinorelbine - Cohort A

EXPERIMENTAL

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 fluorescence in situ hybridization (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

Trastuzumab and Vinorelbine - Main Cohort

EXPERIMENTAL

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

Interventions

trastuzumab DRUG

Trastuzumab and Vinorelbine - Cohort A; Trastuzumab and Vinorelbine - Main Cohort

vinorelbine DRUG

Also known as: navelbine

Trastuzumab and Vinorelbine - Cohort A; Trastuzumab and Vinorelbine - Main Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• Genentech, Inc.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Parsons HA, Macrae ER, Guo H, Li T, Barry WT, Tayob N, Wulf GM, Isakoff SJ, Krop IE. Phase II Single-Arm Study to Assess Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2-Negative Tumors and HER2-Positive Circulating Tumor Cells. JCO Precis Oncol. 2021 Nov;5:896-903. doi: 10.1200/PO.20.00461.

  PMID: 34994617 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Limitations and Caveats

The study terminated early due to insufficient response per statistical design.

Results Point of Contact

• Title: Ian Krop, MD, PhD
• Organization: Dana-Farber Cancer Institute

Ian_Krop@dfci.harvard.edu

617.632.6973

Study Officials

• Ian Krop, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: The analysis was performed for 2 separate cohorts due to a change in study conduct during the trial (see arm description).

Study Record Dates

• First Submitted: August 18, 2010
• First Posted: August 20, 2010
• Study Start: November 1, 2010
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2018
• Last Updated: January 23, 2019
• Results First Posted: May 24, 2017

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)