Trastuzumab and Oxaliplatin in Patients With Metastatic Breast Cancer

Sponsor
SCRI Development Innovations, LLC (Other)
Overall Status
Completed
CT.gov ID
NCT00297596
Collaborator
Sanofi (Industry)
25
7
1
56
3.6
0.1

Study Details

Study Description

Brief Summary

This is a phase II study of the combination of oxaliplatin and trastuzumab as first or second line therapy in patients with stage IV, metastatic breast cancer

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Eligible patients will receive a minimum of six cycles of combination therapy. If a patient is still responding to the oxaliplatin at 6 cycles, the oxaliplatin may be continued with the trastuzumab up to 10 cycles at the investigator's discretion. After discontinuing the oxaliplatin/trastuzumab combination, patients should continue with single agent trastuzumab until disease progression.

Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes. Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles.

For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab

Study Design

Study Type:
Interventional
Actual Enrollment :
25 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of Trastuzumab and Oxaliplatin in Patients With Metastatic Breast Cancer
Study Start Date :
Feb 1, 2006
Actual Primary Completion Date :
Oct 1, 2008
Actual Study Completion Date :
Oct 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intervention

Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days.

Drug: Trastuzumab
Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
Other Names:
  • Herceptin
  • Drug: Oxaliplatin
    Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab
    Other Names:
  • Eloxatin
  • Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [18 months]

      Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: 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.

    Secondary Outcome Measures

    1. Time to Progression [18 months]

      Time-to-progression was defined as the interval from first study treatment until the date that breast cancer progression was documented, other treatment was given, or death occurred.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Females ≥ 18 years of age

    • Histologically confirmed breast cancer that is HER2/neu positive (3+ by IHC or FISH +) and evidence of metastatic disease. Tumor may be of any estrogen and progesterone receptor type

    • Measurable disease by RECIST and an ECOG ≤ 2

    • Patients with known evidence of brain metastases are eligible if they are asymptomatic and have completed all therapy (surgery, radiotherapy, and/or steroids)

    • Baseline LVEF value within the institutional normal range

    • Any number of prior hormonal therapy treatments in the adjuvant setting or for metastatic disease. A subject must have progressed on hormonal therapy and all hormonal therapy (including birth control pills) must be discontinued at study entry.

    • Prior chemotherapy in the adjuvant setting and up to one prior chemotherapy regimen for metastatic disease is allowed.

    • Patients may have received one prior trastuzumab/chemotherapy containing regimen or prior single agent trastuzumab.

    • Prior radiation therapy in the adjuvant setting or for metastatic disease, provided it was not to the only site of evaluable disease.

    • All prior chemotherapy, trastuzumab and radiation therapy should be completed > 2 weeks before enrollment.

    • Patients receiving bisphosphonate therapy are eligible. However, if bisphosphonate were started within < 2 months prior to enrollment, the bone lesions will not be evaluated for response and the patient must have another site of metastatic disease that is either measurable or evaluable for response.

    • Patients must have recovered from toxicities due to prior therapy.

    • Lab values in accordance with the protocol

    • Patients must be nonpregnant and nonlactating. Patients of childbearing potential must implement an effective method of contraception during the study (birth control pills are not allowed).

    Exclusion Criteria:
    • Bone only disease are ineligible

    • Patients who received more than 1 prior chemotherapy regimen for metastatic disease are ineligible.

    • Patients with a history of other cancers except curatively-treated carcinoma of the cervix in situ or non-melanomatous skin cancer.

    • Active serious infection or other underlying medical condition that would impair their ability to receive protocol treatment.

    • Uncontrolled nervous system metastases

    • Dementia or significantly altered mental status that would interfere with proper consenting.

    • Receiving other investigational therapy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Graves-Gilbert Clinic Bowling Green Kentucky United States 42101
    2 Hematology Oncology Life Center Alexandria Louisiana United States 71301
    3 Baton Rouge General Medical Center Baton Rouge Louisiana United States 70806
    4 Oncology Hematology Care Cincinnati Ohio United States 45242
    5 Spartanburg Regional Medical Center Spartanburg South Carolina United States 29303
    6 Chattanooga Oncology and Hematology Associates Chattanooga Tennessee United States 37404
    7 Tennessee Oncology, PLLC Nashville Tennessee United States 37205

    Sponsors and Collaborators

    • SCRI Development Innovations, LLC
    • Sanofi

    Investigators

    • Principal Investigator: Denise A. Yardley, MD, SCRI Development Innovations, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT00297596
    Other Study ID Numbers:
    • SCRI BRE 77
    First Posted:
    Feb 28, 2006
    Last Update Posted:
    Oct 28, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by SCRI Development Innovations, LLC
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Oxaliplatin/Trastuzumab
    Arm/Group Description Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days. Oxaliplatin : Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab Trastuzumab : Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
    Period Title: Overall Study
    STARTED 25
    COMPLETED 25
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Oxaliplatin/Trastuzumab
    Arm/Group Description Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days. Oxaliplatin : Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab Trastuzumab : Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
    Overall Participants 25
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    59
    Sex: Female, Male (Count of Participants)
    Female
    25
    100%
    Male
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    25
    100%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
    Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: 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.
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Oxaliplatin/Trastuzumab
    Arm/Group Description Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days. Oxaliplatin : Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab Trastuzumab : Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
    Measure Participants 25
    Number (95% Confidence Interval) [percentage of participants]
    20
    80%
    2. Secondary Outcome
    Title Time to Progression
    Description Time-to-progression was defined as the interval from first study treatment until the date that breast cancer progression was documented, other treatment was given, or death occurred.
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Oxaliplatin/Trastuzumab
    Arm/Group Description Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days. Oxaliplatin : Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab Trastuzumab : Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
    Measure Participants 25
    Median (Full Range) [months]
    1.7

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Oxaliplatin/Trastuzumab
    Arm/Group Description Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days. Oxaliplatin : Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab Trastuzumab : Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
    All Cause Mortality
    Oxaliplatin/Trastuzumab
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Oxaliplatin/Trastuzumab
    Affected / at Risk (%) # Events
    Total 7/25 (28%)
    Gastrointestinal disorders
    Perforated appendix 1/25 (4%) 1
    Immune system disorders
    Allergic reaction 1/25 (4%) 1
    Musculoskeletal and connective tissue disorders
    Pathologic fracture of let proximal humeral diaphysis 1/25 (4%) 1
    Pathologic fracture of right proximal humeral diaphysis 1/25 (4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Respiratory failure secondary to metastatic disease 1/25 (4%) 1
    Breast cancer 1/25 (4%) 1
    Progressive disease 1/25 (4%) 1
    Respiratory, thoracic and mediastinal disorders
    Right lower lobe pneumonia 1/25 (4%) 1
    Massive pleural effusion with total collapse of right lung 1/25 (4%) 1
    Other (Not Including Serious) Adverse Events
    Oxaliplatin/Trastuzumab
    Affected / at Risk (%) # Events
    Total 20/25 (80%)
    Blood and lymphatic system disorders
    Hemoglobin 18/25 (72%) 48
    Leukocytes (total WBC) 12/25 (48%) 34
    Neutrophils/ granulocytes (ANC/AGC) 4/25 (16%) 16
    Platelets 9/25 (36%) 21
    Endocrine disorders
    Hot flashes/flushes 2/25 (8%) 4
    Gastrointestinal disorders
    Nausea 13/25 (52%) 29
    Diarrhea 15/25 (60%) 38
    Vomiting 5/25 (20%) 9
    Taste Alteration 2/25 (8%) 3
    Anorexia 7/25 (28%) 10
    Constipation 6/25 (24%) 10
    Dehydration 2/25 (8%) 2
    Heartburn/dypepsia 4/25 (16%) 4
    Reflux 2/25 (8%) 4
    General disorders
    Fatigue 20/25 (80%) 62
    Allergic Reaction 2/25 (8%) 3
    Fever 2/25 (8%) 2
    Insomnia 4/25 (16%) 8
    Pain (NOS) 18/25 (72%) 42
    Weakness 2/25 (8%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/25 (16%) 6
    Myalgia 2/25 (8%) 3
    Nervous system disorders
    Neuropathy - Sensory 17/25 (68%) 52
    Mood Alteration - Depression 2/25 (8%) 5
    Neuropathy - Motor 2/25 (8%) 3
    Pain (headache) 2/25 (8%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 4/25 (16%) 8
    Dyspnea 4/25 (16%) 4
    Pulmonary/Upper respiratory 8/25 (32%) 14
    Skin and subcutaneous tissue disorders
    Hair loss/alopecia 3/25 (12%) 4
    Nail Changes 2/25 (8%) 3
    Dermatology/Skin 8/25 (32%) 10

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.

    Results Point of Contact

    Name/Title John D. Hainsworth, MD
    Organization Sarah Cannon Research Institute
    Phone 877-691-7274
    Email ASKSarah@scresearch.net
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT00297596
    Other Study ID Numbers:
    • SCRI BRE 77
    First Posted:
    Feb 28, 2006
    Last Update Posted:
    Oct 28, 2021
    Last Verified:
    Oct 1, 2021