To Reduce the Use of Chemotherapy in Postmenopausal Patients With ER-positive and HER2-positive Breast Cancer (TOUCH)

  • STATUS
    Recruiting
  • End date
    Mar 30, 2022
  • participants needed
    144
  • sponsor
    International Breast Cancer Study Group
Updated on 30 January 2021
paclitaxel
cancer
estrogen
breast cancer
endocrine therapy
metastasis
neutrophil count
hormone therapy
pertuzumab
HER2
primary tumor
trastuzumab
tamoxifen
estradiol
erbb2
estrogen receptor
palbociclib
invasive breast cancer
her2/neu-positive breast cancer
letrozole
mammogram
core needle biopsy
muga scan

Summary

This is a phase II open-label, multicentre, randomized trial. The study assesses the treatment of postmenopausal patients with hormone receptor positive/HER2 positive early breast cancer with neoadjuvant palbociclib in combination with hormonal therapy and HER2 blockade, versus the treatment with paclitaxel in combination with HER2 blockade.

Description

TOUCH is an open label, international, phase II neoadjuvant trial which will assess the treatment of elderly patients with hormone receptor positive / human epidermal growth factor receptor-2 (HER2) positive early breast cancer with neoadjuvant palbociclib in combination with hormonal therapy and HER2 blockade, versus the treatment with paclitaxel in combination with HER2 blockade.

The neo-adjuvant setting was chosen to evaluate these therapy combinations in a short time-frame and to provide access to biomaterial both at baseline and after the end of the treatment, at surgery. Biopsy specimens will be analyzed at the end of the trial by gene-expression profiling to assess RBsig status. This marker may represent a tool to identify the participants who are more likely to benefit from a chemotherapy-free regimen in this population.

Palbociclib is a potent, highly selective, reversible, orally active, inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6), therefore inhibiting cell growth and can be safely and effectively administered to older patients without need for dose adjustment based solely on age. Treatment de-escalation, namely harnessing and taking maximum advantage of targeted therapies vs conventional treatment (chemotherapy) in order to limit side effects, is particularly appealing in the older population.

Clinical data from the HR positive /HER2 negative setting show that combinations of palbociclib and letrozole are safe and effective. These combinations have not yet been tested in the HR positive /HER2 positive population that the investigators include in this trial. However, combinations of trastuzumab and endocrine treatment (ET), including letrozole have shown to be safe and to have some additional activity compared to ET alone in the HR positive /HER2 positive population. Therefore, the role of palbociclib in addition to letrozole and trastuzumab plus pertuzumab needs to be further studied.

Current standard of care for treatment of HER2 positive BC incorporates chemotherapy and anti-HER2 agents, with chemotherapy regimens of sequential anthracyclines and taxanes, used as single agents or in combination with other chemotherapy drugs. Trastuzumab is often administered concurrently with a single agent taxane to avoid the possible additive cardiac toxicity of combinations of anthracycline containing regimens and trastuzumab.

A regimen of weekly paclitaxel and trastuzumab plus pertuzumab was chosen as the comparator arm in this trial. More aggressive chemotherapy may not be justified in this population and trial participants may receive additional treatment after surgery, at the discretion of the treating doctor.

Preclinical and clinical rationale exists to support the proposal that palbociclib may represent a valuable option for increasing the activity of ET and anti-HER2 agents, such that a triple combination with these agents could prove superior to a standard treatment with chemotherapy and anti-HER2 agents.

The investigators hypothesize that the combination of palbociclib, letrozole and trastuzumab plus pertuzumab proposed in this trial will be more efficacious compared to the combinations of anti-HER2 agents and ET reported in other trials.

In 2019, it is estimated that of 260,600 newly diagnosed cases of invasive breast cancer in the United States, 82% occurred in women aged 50 or over. Furthermore, of the 41,760 breast cancer-related deaths in the same year, 90% occurred in this predominantly post-menopausal age group. Around 40% of BCs occur in women aged 65 and older. Of these, 10-15% have tumors that overexpress HER2. Elderly patients are generally underrepresented in clinical trials and may benefit from anti-HER2 agents as much as the younger population. Post-menopausal patients with HR positive /HER2 positive BC represent a unique group of patients with an unmet clinical need. This population is the focus of the TOUCH trial.

Details
Condition Breast Cancer, HER2 Positive Breast Cancer, Breast Cancer Diagnosis, Estrogen Receptor Positive Tumor, breast carcinoma, her2/neu-positive breast cancer, her2-positive breast cancer, cancer, breast
Treatment Paclitaxel, Trastuzumab, Letrozole, Pertuzumab, Palbociclib
Clinical Study IdentifierNCT03644186
SponsorInternational Breast Cancer Study Group
Last Modified on30 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Are you female?
Do you have any of these conditions: Estrogen Receptor Positive Tumor or Breast Cancer or HER2 Positive Breast Cancer?
Do you have any of these conditions: breast carcinoma or Breast Cancer Diagnosis or her2/neu-positive breast cancer or HER2 Positive Breast Cancer or cancer, breast or Breast Cancer or he...?
Do you have any of these conditions: cancer, breast or Estrogen Receptor Positive Tumor or breast carcinoma or HER2 Positive Breast Cancer or her2/neu-positive breast cancer or her2-posit...?
Do you have any of these conditions: HER2 Positive Breast Cancer or Breast Cancer Diagnosis or Estrogen Receptor Positive Tumor or breast carcinoma or her2-positive breast cancer or cance...?
Do you have any of these conditions: Breast Cancer or Breast Cancer Diagnosis or Estrogen Receptor Positive Tumor or cancer, breast or her2/neu-positive breast cancer or her2-positive bre...?
Do you have any of these conditions: breast carcinoma or HER2 Positive Breast Cancer or her2/neu-positive breast cancer or Estrogen Receptor Positive Tumor or Breast Cancer or Breast Canc...?
Histologically confirmed invasive breast cancer, with the following characteristics
Early breast cancer with tumor size >1 cm (as measured by at least one of the required examination methods of clinical examination, mammography and ultrasonography)
No clinical evidence of regional lymph node metastasis (via physical and/or radiological exam) (cN0) OR
Clinical evidence of cN1 status, defined by nodal involvement limited to clinically or radiologically detectable metastasis to movable ipsilateral level I, II axillary lymph node(s)
No evidence of metastasis (M0)
Postmenopausal, defined by women with
Prior bilateral surgical oophorectomy; OR
Amenorrhea and age 60 years; OR
Age <60 years and amenorrhea for 12 or more consecutive months in the absence of alternative pathological or physiological cause (including chemotherapy, tamoxifen, toremifene, ovarian suppression, or hormonally-based contraception) plus FSH and serum estradiol levels within the laboratory's reference ranges for postmenopausal women
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Primary tumor must have positive estrogen receptor (ER) 10%
Primary tumor must be HER2-positive (by IHC and/or ISH)
Baseline LVEF 55% measured by Echocardiography (preferred) or MUGA scan
Normal hematologic status
Absolute neutrophil count 1500/mm3 (1.5 109/L)
Platelets 100 109/L
Hemoglobin 9 g/dL (90 g/L)
Normal renal function: serum creatinine 1.5 ULN
Normal liver function
Serum total bilirubin 1.5 upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (<2 ULN) is allowed
AST or ALT 2.5 ULN
Alkaline phosphatase 2.5 ULN
Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization
The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines
The patient agrees in writing to make tumor (mandatory diagnostic core biopsy and surgical specimen) available for submission for central pathology review and to conduct translational studies as part of this protocol

Exclusion Criteria

Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) (T4 according to AJCC 8th edition cancer staging TNM)
Inflammatory breast cancer
Bilateral invasive breast cancer
Received any prior treatment for primary invasive breast cancer
Any active tumor of non-breast-cancer histology
Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA functional classification II), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism
Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety
Contraindications or known hypersensitivity to any of the trial medications or excipients
Treatment with any investigational agents within 30 days prior to expected start of trial treatment
Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection
Evidence via physical and/or radiological exam of cN2 or cN3 nodal involvement defined by: metastasis to ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted, OR involvement of ipsilateral infraclavicular, internal mammary and/or supraclavicular lymph node(s)
History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis. A history of prior radiation pneumonitis is not considered an exclusion criterion
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