TerminatedNCT03329378Updated Aug 22, 2023Results posted

Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

A Phase 2 interventional study of Docetaxel and Carboplatin in Locally Advanced Breast Cancer, sponsored by Icahn School of Medicine at Mount Sinai. Terminated at 3 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-22.

Sponsored by Icahn School of Medicine at Mount Sinai · Phase 2, Interventional, and Treatment

Why this study was terminated

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.

Phase: Phase 2
Study type: Interventional
Enrollment: 7
Allocation: Randomized
Ages: 18 Years and older
Sex: Female

Study 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.
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 studied

Locally Advanced Breast Cancer

Keywords

Neoadjuvant chemotherapy
locally advanced breast cancer
Her2neu

In context

Lead sponsor

Icahn School of Medicine at Mount Sinai is the lead sponsor of 772 studies on the registry; 175 are open to participants now.

Of its 124 completed or terminated interventional studies of FDA-regulated products, 83 (67%) have results posted.

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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)
- 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.

Exclusion criteria

Exclusion Criteria:

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;
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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 7 participants (actual)

Study arms

Active comparator
ddACTHP
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
Drug: Pertuzumab · Drug: Trastuzumab · Drug: Paclitaxel · Drug: Doxorubicin · Drug: Cyclophosphamide
Active comparator
TCHP
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.
Drug: Docetaxel · Drug: Carboplatin · Drug: Trastuzumab · Drug: Pertuzumab · Drug: Pegfilgrastim · Drug: Paclitaxel

Interventions

DrugDocetaxel
Docetaxel 75mg/m2 IV, day 1
DrugCarboplatin
Carboplatin AUC 6 IV, day 1
DrugTrastuzumab
Trastuzumab 8mg/kg IV initial dose, followed by 6mg/kg IV , day 1
DrugPertuzumab
Pertuzumab 840 mg IV initial dose followed by 420 mg IV, day 1
DrugPegfilgrastim
Pegfilgrastim 6mg SC, day 2 Cycled as per arm
DrugTrastuzumab
Trastuzumab 6mg/kg every 21 days to complete 1 year
DrugPaclitaxel
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.
DrugDoxorubicin
Doxorubicin 60 mg/m2 IV day 1
DrugCyclophosphamide
Cyclophosphamide 600 mg/m2 IV day 1
DrugPaclitaxel
80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15

What researchers measure

Primary outcomes

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.
Time frame: 2 years

Secondary outcomes

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.
Time frame: 2 years
Number of Non-cardiac Toxicities
The frequency of adverse events categorized using CTCAE v4.03
Time frame: 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.
Time frame: 2 years
Number of Participants Alive at the End of the Study
Overall Survival - Number of participants alive at the end of the study.
Time frame: 2 years

Results

Posted Aug 22, 2023

Participant flow

Participant flow — Overall Study
Milestone	ddACTHP	TCHP
Started	2	5
Completed	2	5
Not completed	0	0

Outcome measures

PrimaryNumber 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.

Time frame:: 2 years
Reported as:: Count of participants · Participants

Number of Participants With Pathologic Complete Response (pCR)
Participants	ddACTHP	TCHP
Number of Participants With Pathologic Complete Response (pCR)	1	4

SecondaryNumber 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.

Time frame:: 2 years
Reported as:: Number · events

Number of Cardiac Toxicity Events
events	ddACTHP	TCHP
Number of Cardiac Toxicity Events	2	2

SecondaryNumber of Non-cardiac Toxicities

The frequency of adverse events categorized using CTCAE v4.03

Time frame:: 2 years
Reported as:: Number · events

Number of Non-cardiac Toxicities
events	ddACTHP	TCHP
Number of Non-cardiac Toxicities	63	120

SecondaryNumber 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.

Time frame:: 2 years
Reported as:: Count of participants · Participants

Number of Participants With Breast Conservation
Participants	ddACTHP	TCHP
Number of Participants With Breast Conservation	0	0

SecondaryNumber of Participants Alive at the End of the Study

Overall Survival - Number of participants alive at the end of the study.

Time frame:: 2 years
Reported as:: Count of participants · Participants

Number of Participants Alive at the End of the Study
Participants	ddACTHP	TCHP
Number of Participants Alive at the End of the Study	2	5

Adverse events

Collected over 2 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
ddACTHP	0/2 (0%)	0/2 (0%)	2/2 (100%)
TCHP	0/5 (0%)	0/5 (0%)	5/5 (100%)

Most frequent other events

Showing 10 of 58

Most frequent other events
Event	ddACTHP	TCHP
AnemiaBlood and lymphatic system disorders	2/2	3/5
chest painCardiac disorders	2/2	0/5
diarrheaGastrointestinal disorders	0/2	5/5
fatigueGeneral disorders	2/2	4/5
HeadacheNervous system disorders	2/2	1/5
Peripheral sensory neuropathyNervous system disorders	2/2	2/5
WBC decreaseBlood and lymphatic system disorders	2/2	3/5
NauseaGastrointestinal disorders	1/2	4/5
dry skinSkin and subcutaneous tissue disorders	0/2	3/5
AlopeciaSkin and subcutaneous tissue disorders	1/2	1/5

Baseline characteristics

Age, Continuous
Age, Continuous(years)	ddACTHP	TCHP	Total
Mean	45 ± 14.14	54.5 ± 15.05	49.75 ± 14.75

Sex: Female, Male
Sex: Female, Male(Participants)	ddACTHP	TCHP	Total
Female	2	5	7
Male	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	ddACTHP	TCHP	Total
Hispanic or Latino	1	2	3
Not Hispanic or Latino	1	3	4
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	ddACTHP	TCHP	Total
American Indian or Alaska Native	0	0	0
Asian	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	2	3
White	1	1	2
More than one race	0	1	1
Unknown or Not Reported	0	0	0

Study locations

3 sites

Mount Sinai Beth Israel
New York, New York 10011, United States
Mount Sinai West
New York, New York 10019, United States
Icahn School of Medicine at Mount Sinai
New York, New York 10029, United States

References and documents

Study documents

Protocol and statistical analysis plan · Aug 23, 2019
Informed consent form · Jun 29, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 22, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03329378
Lead sponsor: Icahn School of Medicine at Mount Sinai
Responsible party: Aarti S. Bhardwaj (Assistant Professor, Icahn School of Medicine at Mount Sinai) — Principal investigator
First posted: Nov 6, 2017
Start date: Jan 24, 2019
Primary completion: Mar 7, 2021
Completion: Mar 7, 2021
Results posted: Aug 22, 2023
Last update: Aug 22, 2023

Study contacts

Aarti Bhardwaj, MD

principal investigator · Icahn School of Medicine at Mount Sinai

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Docetaxel · Carboplatin · Pegfilgrastim · Doxorubicin · Cyclophosphamide

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