Trastuzumab and Oxaliplatin in Patients With Metastatic Breast Cancer
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
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:
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
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.- SCRI BRE 77
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
| 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%
|
| 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
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 |
| ASKSarah@scresearch.net |
- SCRI BRE 77