Locally Advanced Breast CancerPhase 2NCT03329378
Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer
A Phase 2 study testing Docetaxel, Carboplatin and Trastuzumab in people with Locally Advanced Breast Cancer, run by Icahn School of Medicine at Mount Sinai at 3 sites in United States.
Trial summary
Primary Objective: Determination of pathologic complete response (pCR) rates Secondary Objective: Determination of cardiac toxicity as measured by: composite of LVEF, longitudinal strain and troponin. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Locally Advanced Breast Cancer
- What is being tested?
- Docetaxel, Carboplatin and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Jan 2019to 7 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
- Female
- 18 years or older
- ECOG performance status of 0 or 1
- Eligible tumors must meet one of the following criteria:
- Operable (T1c, T2-3, N0-1, M0)
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- Locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0)
- Inflammatory breast cancer (T4d, any N, M0)
- Staging evaluation:
- History and physical exam, cbc, chemistry profile
- CT Chest/Abdomen/Pelvis and a bone scan or PET/CT as needed
- Diagnosis of invasive adenocarcinoma made by core needle biopsy
- Breast cancer determined to be:
- Confirmed HER2-positive : (ASCO CAP guidelines, 10/7/2013)
- IHC 3+ based on circumferential membrane staining that is complete, intense
- ISH positive based on:
- Single probe average HER2 copy number ≥ 6 signals/cell
- Dual probe HER2/CEP 17 ratio ≥ 2.0 with an average HER2 copy number ≥ 4.0 signals/cell
- Dual probe HER2/CEP 17 ratio ≥ 2.0, with an average HER2 copy number of < 4.0 signals/cell
- Dual probe HER2/CEP 17 ratio < 2.0 with the average HER2 copy number of ≥ 6.0 signals/cell
- any ER or PR receptor status
- LVEF assessment by echocardiogram within 30 days of initiation; EF of ≥ 55% considered normal.
- Normal troponin I level at baseline
- Blood counts must meet the following criteria:
- ANC greater than or equal to 1500/mm3
- Platelet count greater than or equal to 100,000/mm3
- Hemoglobin greater than or equal to 10 g/dL
- Serum creatinine less than or equal 2.5 mg/100ml
- Adequate hepatic function by these criteria: total bilirubin must be less than or equal to 1.5 x the ULN for the lab unless the patient has a bilirubin elevation great than the ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and AST must be less than or equal to 1.5 x ULN for the lab. Both alkaline phosphatase and AST may not both be greater than the ULN.
- Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the requirements are met as above
- Patients with alkaline phosphatase that is > ULN but less than or equal to 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease.
Who cannot join
- Patients with a history of decompensated congestive heart failure or an EF < 55% will be excluded
- Cardiac disease that would preclude the use of the drugs included in the above regimens. This includes but is not confined to:
- Active cardiac disease:
- angina pectoris requiring the use of anti-anginal medication;
- ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
- conduction abnormality requiring a pacemaker;
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- supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
- clinically significant valvular disease
- symptomatic pericarditis
- pulmonary hypertension
- History of cardiac disease:
- myocardial infarction;
- congestive heart failure; or
- cardiomyopathy
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mount Sinai Beth Israel
New York, New York, 10011
Mount Sinai West
New York, New York, 10019
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Phase II Randomized Trial Evaluating Neoadjuvant Dose-Dense Doxorubicin/Cyclophosphamide Followed by Paclitaxel/Trastuzumab/Pertuzumab (AC THP) and Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) For Early Her2Neu Positive Breast Cancer
Primary Objective:
- Determination of pathologic complete response (pCR) rates
Read more
Secondary Objective:
- Determination of cardiac toxicity as measured by: composite of LVEF, longitudinal strain and troponin.
- Breast conservation rates
- Overall survival
Study Design
- Approximately 34-74 patients with Her2 positive, Stage II-regional IV breast cancer will be enrolled.
- Patients will be stratified by ER/PR status.
- They will be randomized to ddACTHP vs TCHP.
- Initially, 17 patients will be randomly assigned to each treatment arm.
- If 3 or fewer patients have a pCR, then that arm will be terminated and no further patients will be entered on that treatment arm.
- If 4 or more patients obtain a pCR, 20 additional patients (total of 37 patients) will be randomized to that treatment arm.
- If 11 or more patients out of 37 have a pCR, the treatment will be of interest for further study.
- Conditions
- Locally Advanced Breast Cancer
- Being tested
- Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim
- Keywords
- Neoadjuvant chemotherapy, locally advanced breast cancer, Her2neu
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Docetaxel 75mg/m2 IV, day 1
CarboplatinDrug
Carboplatin AUC 6 IV, day 1
TrastuzumabDrug
Trastuzumab 8mg/kg IV initial dose, followed by 6mg/kg IV , day 1
PertuzumabDrug
Pertuzumab 840 mg IV initial dose followed by 420 mg IV, day 1
PegfilgrastimDrug
Pegfilgrastim 6mg SC, day 2 Cycled as per arm
TrastuzumabDrug
Trastuzumab 6mg/kg every 21 days to complete 1 year
PaclitaxelDrug
Titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
DoxorubicinDrug
Doxorubicin 60 mg/m2 IV day 1
CyclophosphamideDrug
Cyclophosphamide 600 mg/m2 IV day 1
PaclitaxelDrug
80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15
| Study group | Role | What they receive |
|---|---|---|
| ddACTHP | Active comparator | Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC
Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks
Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year Receives: Drug: Pertuzumab; Drug: Trastuzumab; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide |
| TCHP | Active comparator | TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour. Receives: Drug: Docetaxel; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Pegfilgrastim; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Pathologic Complete Response (pCR)
Pathologic complete response (pCR) defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy.
Measured: 2 years
Secondary outcomes (4)
Number of Cardiac Toxicity Events
Determination of cardiac toxicity as measured by LVEF, longitudinal strain and troponin.
Left ventricular ejection fraction (LVEF) measurement of amount of blood being pumped out of the left ventricle of the heart with each contraction.
Peak systolic longitudinal strain is calculated by averaging the values of peak systolic strain in the basal, mid and apical segments of the LV in 4-, 3- and 2-chamber views on echocardiograms. A value of <-18% or a >15% decline in strain from patient's baseline value will be used as a cut-off value.
A value of troponin I > 0.08 ng/ml will be considered elevated.
Measured: 2 years
Number of Non-cardiac Toxicities
The frequency of adverse events categorized using CTCAE v4.03
Measured: 2 years
Number of Participants With Breast Conservation
Number of participants with breast-conserving surgery for patients for whom mastectomy was planned before treatment. It would be based on surgical opinion at time of surgery if the tumor was appropriately "downstaged" to perform breast conserving surgery on patients previously recommended to have a mastectomy.
Measured: 2 years
Number of Participants Alive at the End of the Study
Overall Survival - Number of participants alive at the end of the study.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start24 Jan 2019
- Primary completion7 Mar 2021
- Study completion7 Mar 2021
Why it stopped: Data Safety Monitoring Board is in agreement with the study findings so far and the stopping rule has been met, which suspends the study treatment arms in March 2021.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aarti S. Bhardwaj, Icahn School of Medicine at Mount Sinai
- Investigators
- Aarti Bhardwaj, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03329378
- Sponsor's protocol ID
- GCO 17-1585
- Status last verified
- Aug 2023
- First submitted
- 30 Oct 2017
- Last updated
- 22 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Trial Evaluating Neoadjuvant Dose-Dense Doxorubicin/Cyclophosphamide Followed by Paclitaxel/Trastuzumab/Pertuzumab (AC THP) and Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) For Early Her2Neu Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT03329378
- Acronym / sponsor ID
- GCO 17-1585
- Conditions
- Locally Advanced Breast Cancer
- Keywords
- Neoadjuvant chemotherapy, locally advanced breast cancer, Her2neu
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data Safety Monitoring Board is in agreement with the study findings so far and the stopping rule has been met, which suspends the study treatment arms in March 2021.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 24 Jan 2019 (actual)
- Primary completion
- 7 Mar 2021 (actual)
- Study completion
- 7 Mar 2021 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Posted 22 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
- Determination of pathologic complete response (pCR) rates
Secondary Objective:
- Determination of cardiac toxicity as measured by: composite of LVEF, longitudinal strain and troponin.
- Breast conservation rates
- Overall survival
Study Design
- Approximately 34-74 patients with Her2 positive, Stage II-regional IV breast cancer will be enrolled.
- Patients will be stratified by ER/PR status.
- They will be randomized to ddACTHP vs TCHP.
- Initially, 17 patients will be randomly assigned to each treatment arm.
- If 3 or fewer patients have a pCR, then that arm will be terminated and no further patients will be entered on that treatment arm.
- If 4 or more patients obtain a pCR, 20 additional patients (total of 37 patients) will be randomized to that treatment arm.
- If 11 or more patients out of 37 have a pCR, the treatment will be of interest for further study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ddACTHP | Active comparator | Drug: Pertuzumab, Drug: Trastuzumab, Drug: Paclitaxel, Drug: Doxorubicin, Drug: CyclophosphamideDoxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year |
| TCHP | Active comparator | Drug: Docetaxel, Drug: Carboplatin, Drug: Trastuzumab, Drug: Pertuzumab, Drug: Pegfilgrastim, Drug: PaclitaxelTCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
- Female
- 18 years or older
- ECOG performance status of 0 or 1
- Eligible tumors must meet one of the following criteria:
Key exclusion criteria (14 listed)
- Patients with a history of decompensated congestive heart failure or an EF < 55% will be excluded
- Cardiac disease that would preclude the use of the drugs included in the above regimens. This includes but is not confined to:
- Active cardiac disease:
- angina pectoris requiring the use of anti-anginal medication;
- ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelDocetaxel 75mg/m2 IV, day 1 | Drug | TCHP |
| CarboplatinCarboplatin AUC 6 IV, day 1 | Drug | TCHP |
| TrastuzumabTrastuzumab 8mg/kg IV initial dose, followed by 6mg/kg IV , day 1 | Drug | TCHP |
| PertuzumabPertuzumab 840 mg IV initial dose followed by 420 mg IV, day 1 | Drug | TCHP, ddACTHP |
| PegfilgrastimPegfilgrastim 6mg SC, day 2 Cycled as per arm | Drug | TCHP |
| TrastuzumabTrastuzumab 6mg/kg every 21 days to complete 1 year | Drug | TCHP, ddACTHP |
| PaclitaxelTitrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour. | Drug | TCHP, ddACTHP |
| DoxorubicinDoxorubicin 60 mg/m2 IV day 1 | Drug | ddACTHP |
| CyclophosphamideCyclophosphamide 600 mg/m2 IV day 1 | Drug | ddACTHP |
| Paclitaxel80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 | Drug | ddACTHP |
Primary outcome
Number of Participants With Pathologic Complete Response (pCR)
Time frame: 2 years
Pathologic complete response (pCR) defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy.
4 secondary outcomes
Number of Cardiac Toxicity Events
Time frame: 2 years
Number of Non-cardiac Toxicities
Time frame: 2 years
Number of Participants With Breast Conservation
Time frame: 2 years
Number of Participants Alive at the End of the Study
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aarti Bhardwaj, MD principal investigator
Icahn School of Medicine at Mount Sinai
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel, Carboplatin and Trastuzumab in people with Locally Advanced Breast Cancer, run by Icahn School of Medicine at Mount Sinai at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Pathologic Complete Response (pCR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.