Description:
This phase II trial studies how well panitumumab, carboplatin and paclitaxel work in treating
patients with newly diagnosed triple negative breast cancer that is limited to the breast and
possibly to the nearby lymph nodes (locally advanced). This treatment study is linked to
NCI-2015-00191 protocol, which uses a baseline biopsy to determine the neoadjuvant therapy
that matches the sub-type of triple negative breast cancer (TNBC). Immunotherapy with
panitumumab, may induce changes in body's immune system and may interfere with the ability of
tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and
paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Giving
panitumumab, carboplatin and paclitaxel before surgery may be an effective treatment for
breast cancer by making the tumor smaller and reducing the amount of normal tissue that needs
to be removed.
Title
- Brief Title: Women's MoonShot: Neoadjuvant Treatment With PaCT for Patients With Locally Advanced TNBC
- Official Title: Women's Triple-Negative First-Line Study: A Phase II Trial of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy
Clinical Trial IDs
- ORG STUDY ID:
2015-0294
- SECONDARY ID:
NCI-2015-02183
- SECONDARY ID:
2015-0294
- NCT ID:
NCT02593175
Conditions
- Stage I Breast Cancer AJCC v7
- Stage IA Breast Cancer AJCC v7
- Stage IB Breast Cancer AJCC v7
- Stage II Breast Cancer AJCC v6 and v7
- Stage IIA Breast Cancer AJCC v6 and v7
- Stage IIB Breast Cancer AJCC v6 and v7
- Stage III Breast Cancer AJCC v7
- Stage IIIA Breast Cancer AJCC v7
- Stage IIIB Breast Cancer AJCC v7
- Stage IIIC Breast Cancer AJCC v7
- Triple-Negative Breast Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Carboplatin | Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo | Treatment (panitumumab, paclitaxel, carboplatin) |
Paclitaxel | Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat | Treatment (panitumumab, paclitaxel, carboplatin) |
Panitumumab | ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix | Treatment (panitumumab, paclitaxel, carboplatin) |
Purpose
This phase II trial studies how well panitumumab, carboplatin and paclitaxel work in treating
patients with newly diagnosed triple negative breast cancer that is limited to the breast and
possibly to the nearby lymph nodes (locally advanced). This treatment study is linked to
NCI-2015-00191 protocol, which uses a baseline biopsy to determine the neoadjuvant therapy
that matches the sub-type of triple negative breast cancer (TNBC). Immunotherapy with
panitumumab, may induce changes in body's immune system and may interfere with the ability of
tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and
paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Giving
panitumumab, carboplatin and paclitaxel before surgery may be an effective treatment for
breast cancer by making the tumor smaller and reducing the amount of normal tissue that needs
to be removed.
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the pathologic complete response (pCR), residual cancer burden (RCB)-0 and
RCB-I rates of patients with localized TNBC who were treated with panitumumab, carboplatin
and paclitaxel (PaCT) in the neoadjuvant setting.
SECONDARY OBJECTIVES:
I. To estimate progression free survival (PFS) distribution of localized TNBC patients who
were non-responders to initial anthracycline and cyclophosphamide chemotherapy, and who were
treated with the PaCT regimen in the neoadjuvant setting.
II. Determine changes of epidermal growth factor receptor (EGFR) downstream biomarkers one
week after 1 dose of panitumumab.
III. Determine response rate after 4 cycles of PaCT using radiographic imaging. IV. Correlate
pathologic response with EGFR expression as measured by immunohistochemistry (IHC).
V. Determine toxicity associated to 4 cycles of PaCT in the neoadjuvant setting.
VI. Compare pathologic response to 4 cycles of PaCT in EGFR overexpressing tumors versus
(vs.) non-EGFR overexpressing tumors.
VII. Compare pathologic response in tumors to 4 cycles of PaCT vs. 12 weeks of weekly
paclitaxel (using data collected in conjunction with protocol 2014-0185).
EXPLORATORY OBJECTIVES:
I. Determine the correlation between EGFR expression by IHC and the presence of enhanced EGFR
gene signatures at the time of initial tumor biopsy prior to neoadjuvant setting (NACT)
(using gene expression data obtained from the protocol 2014-0185).
II. Determine rates of pCR in patients with EGFR overexpressed tumors identified by gene
signatures (using gene expression data obtained from protocol 2014-0185) and compare to pCR
rates in non-EGFR overexpressed tumors.
III. Determine the correlation between EGFR expression by IHC and the changes of EGFR
downstream changes induced in surgery sample after completion of PaCT regimen.
IV. Determine the change in programmed cell death ligand 1 (PD-L1) glycosylation induced by
panitumumab, and correlation with efficacy.
V. Determine the change after treatment in blood-based markers, if any, and use these to
predict a response to panitumumab treatment.
OUTLINE:
Patients receive panitumumab intravenously (IV) over 30 minutes and paclitaxel IV over 30
minutes on days 1, 8, and 15. Patients also receive carboplatin IV over 30 minutes on day 1.
Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-4 months.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (panitumumab, paclitaxel, carboplatin) | Experimental | Patients receive panitumumab IV over 30 minutes and paclitaxel IV over 30 minutes on days 1, 8, and 15. Patients also receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. | - Carboplatin
- Paclitaxel
- Panitumumab
|
Eligibility Criteria
Inclusion Criteria:
- Patients must have an intact evaluable primary tumor or biopsy proven axillary node
involvement with at least 1.0 centimeter (cm) smallest dimension based on imaging
after neoadjuvant anthracycline-based chemotherapy and prior to initiation of
neoadjuvant chemotherapy under this protocol; baseline measurements and evaluations
must be obtained within 4 weeks of registration to the study; all areas of disease
should be recorded in order to assess response and uniformity of response to therapy
- Triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone
receptor (PR) < 10% by immunohistochemistry (IHC) and human epidermal growth factor
receptor 2 (HER2) 0-1 positive (+) by IHC or 2+, fluorescence in situ hybridization
(FISH) < 2, gene copy number < 4
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1
- Patients must have received at least one dose of an anthracycline based neoadjuvant
regimen; patients are eligible if therapy was discontinued due to disease progression
or therapy intolerance
- Baseline multi-gated acquisition (MUGA) or echocardiogram showing left ventricular
ejection fraction (LVEF) >= 50% within 6 weeks prior to initiation of neoadjuvant
chemotherapy
- Serum creatinine =< 1.5 mg/dl
- Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockcroft-Gault method
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelets >= 100,000/mm^3
- Hemoglobin >= 9.0 g/dL
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3.0 x
upper limit of normal
- Alkaline phosphatase (Alp) =< 2.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN
- Signed informed consent
Exclusion Criteria:
- Patient is unwilling or unable to sign and date the Institutional Review Board (IRB)
approved informed consent
- Patients with less than a 1.0 cm measurable residual disease after neoadjuvant
anthracycline based chemotherapy
- Women that are pregnant or lactating
- Patients with a history of prior malignancy within 5 years of study entry with the
exception of curatively treated non-melanomatous skin cancer or carcinoma in situ of
the cervix or breast
- Patients with a history of stage IV or metastatic disease
- Any serious medical illness, other than that treated by this study, which would limit
survival to less than 1 month or psychiatric illness which would limit informed
consent
- Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus,
acute or chronic active hepatitis B infection
- Patients with a peripheral neuropathy > grade 1
- Patients with a history of serious cardiac events defined as: New York Heart
Association class 3 or 4 heart failure, or history of myocardial infarction, unstable
angina or cerebrovascular accident (CVA) within 6 months of protocol registration
- Patients with a history of PR prolongation or atrioventricular (AV) block
- Patients with a history of prior therapy with paclitaxel and/or carboplatin
- Patients who have received a cumulative dose of doxorubicin of greater than 360 mg/m^2
or epirubicin of greater than 640 mg/m^2
- Patients who concurrently use hormonal therapy and/or concurrent radiation therapy
- Patients who had prior radiation therapy of the primary breast carcinoma or axillary
lymph nodes
- Women of child-bearing potential (WOCBP), defined as all women physiologically capable
of becoming pregnant, must use highly effective methods of contraception during the
study and 8 weeks after; highly effective contraception methods include combination of
any two of the following: placement of an intrauterine device (IUD) or intrauterine
system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository, total
abstinence or male/female sterilization; women are considered post-menopausal and not
of child-bearing potential if they have had 12 months of natural (spontaneous)
amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of
vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks prior to treatment; in the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow up hormone level assessment is she considered not of child-bearing potential
- Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
contraception, during the study and for 8 weeks after the end of treatment
- Negative serum or urine pregnancy test for women within 72 hours of receiving the
first dose of the study medication for women of childbearing potential
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Pathologic compete response (pCR) (residual cancer burden [RCB]-0) or RCB-I response rates of patients with localized triple-negative breast cancer (TNBC) treated with panitumumab, carboplatin and paclitaxel (PaCT) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Will estimate the proportion of patients with pCR (RCB-0) or RCB-I as the response rate along with an appropriate 95% confidence interval. Will estimate the proportion of patients in the remaining RCB categories with confidence intervals as well. |
Secondary Outcome Measures
Measure: | Progression free survival (PFS) |
Time Frame: | Time from enrollment to progression of disease (> 20% increase in tumor size) or death whichever comes first, assessed up to 2 years |
Safety Issue: | |
Description: | PFS distribution will be estimated using the Kaplan-Meier method. |
Measure: | Changes of EGFR levels |
Time Frame: | Baseline up to 1 week after 1 dose of panitumumab |
Safety Issue: | |
Description: | Potential biomarkers of response will be correlated with pathologic response to this treatment using appropriate statistical analyses for the biomarker of interest. |
Measure: | Pathologic complete response (pCR) (residual cancer burden [RCB]-0) or RCB-I response rates of patients treated with panitumumab, carboplatin and paclitaxel (PaCT) |
Time Frame: | Up to 4 courses (84 days) |
Safety Issue: | |
Description: | Assessed by radiographic imaging. The proportion of patients with pCR (RCB-0) or RCB-I as the response rate will be estimated along with an appropriate 95% confidence interval. The proportion of patients in the remaining RCB categories will be estimated with confidence intervals. |
Measure: | Overall survival (OS) |
Time Frame: | Up to 2 years after completion of study treatment |
Safety Issue: | |
Description: | OS distribution will be estimated using the Kaplan-Meier method. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
April 14, 2021