Clinical trial NCT01104935: National Surgical Adjuvant Study of Breast Cancer(N-SAS BC) 07 [RESPECT]
Official title: Evaluation of Trastuzumab Without Chemotherapy as a Postoperative Adjuvant Therapy in HER2 Positive Elderly Breast Cancer Patients: Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Comprehensive Support Project for Oncology Research
Sponsor class: OTHER
First posted: 2010-04-16
Enrollment: 275
Sex: FEMALE
Minimum age (years): 70
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate clinical positioning between trastuzumab (Herceptin) monotherapy (H group) and combination therapy of trastuzumab and chemotherapy (H+CT group) based on a randomized controlled trial in women over 70 years with human epidermal growth factor receptor type-2 (HER2) positive primary breast cancer.

Detailed description: This study is a randomized, comparative trial of postoperative adjuvant therapies in women with HER2 (human epidermal growth factor receptor type-2)-positive primary breast cancer who are ≥70 years of age that will compare trastuzumab (Herceptin®) monotherapy (H group) and trastuzumab in combination with chemotherapy (H+CT group).

The objectives of this study are as follows.

1. To verify the clinical positioning of trastuzumab monotherapy and combined trastuzumab and chemotherapy as postoperative adjuvant therapies for the treatment of HER2-positive primary breast cancer patients who are ≥70 years of age.
2. To evaluate the safety of trastuzumab monotherapy and combined trastuzumab and chemotherapy in patients who are ≥70 years of age. In particular, to evaluate cardiac disorders that are a characteristic adverse drug reaction of trastuzumab as well as geriatric-related concerns including lipid metabolism, cerebral infarction and cognitive disorders.
3. To evaluate overall survival in patients who are ≥70 years of age using trastuzumab monotherapy or combined trastuzumab and chemotherapy.
4. To evaluate health-related quality of life (HRQOL), cost-effectiveness (utility), and conduct a comprehensive geriatric assessment (CGA) in patients who are ≥70 years of age and using trastuzumab monotherapy or combined trastuzumab and chemotherapy.
5. To establish and expand information networks by the participation of practitioners in clinical trials that are involved in general clinical practice and breast cancer.

Eligibility criteria: Inclusion Criteria:

1. Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer.
2. Stage: 1 (tumor size \[pT\] \> 0.5 cm), 2A, 2B or 3A/ M0
3. Female between 70 and 80 years old
4. Primary region is HER 2 positive: either 3+ overexpression by IHC or positive by FISH
5. Baseline left ventricular ejection fraction (LVEF) is ≥55% measured by echocardiography or MUGA scan within 4 weeks before registration.
6. PS: 0-1 (ECOG)
7. Sufficient organ function meeting following criteria within 4 weeks before registration:

   * Leukocyte ≥2500 mm3
   * Neutrophil ≥1500 mm3
   * Platelet ≥100 000 mm3
   * Serum total bilirubin ≤2.0 x upper limit of normal (ULN)
   * ALT (GPT) or AST (GOT) ≤2.5 x ULN
   * Serum creatinine ≤2.0 x ULN
   * ALP ≤2.5 x ULN
8. No previous endocrine therapy or chemotherapy for breast cancer
9. Signed written informed consent

Exclusion Criteria:

1. Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs)
2. Postoperative histological axillary lymph node metastasis ≥4
3. Axillary lymph node is not histologically evaluated
4. Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on policy of site)
5. History of drug-related allergy which could hinder planned treatment
6. Any history or complication of following cardiac disorders

   * History of congestive heart failure, cardiac infarction
   * Complication requires treatment such as: ischemic cardiac disorder, arrhythmia, valvular heart disease
7. Poorly controlled hypertension (ex. Systolic arterial pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg)
8. Poorly controlled diabetes
9. Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living (ADL)
10. Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms
11. Ineligible to the trial based on decision of an investigator

Primary outcomes:
measure: Disease free survival
timeFrame: Patients are followed up for 8 years after initial enrollment (from Oct. 2009 through Oct. 2017).
Secondary outcomes:
measure: Overall survival
timeFrame: Patients are followed up for 8 years after initial enrollment (from Oct. 2009 through Oct. 2017).
measure: Relapse-free survival
timeFrame: Patients are followed up for 8 years after initial enrollment (from Oct. 2009 through Oct. 2017).
measure: Percentage of participants with adverse events as a measure of safety
timeFrame: Evaluations are performed at the time of starting the specified treatment and 2, 6, and 9 month, 1 year, 1 year 6 months, 2 years, 2 years 6 months, and 3 years after the start of treatment. Subsequently, evaluations are done at 1-year intervals.
measure: Health-related QOL (HRQOL)
timeFrame: Evaluations are performed at the time of starting the specified treatment and 2 months, 1 year, and 3 years after the start of treatment.
measure: Cost effectiveness analysis
timeFrame: Data on direct medical costs for the 3-year period after the start of the treatment are obtained from CRF. Data on direct nonmedical costs and indirect costs are obtained from questionnaires 2, 12, and 36 months after starting the treatment.
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
Study officials:
affiliation: Department of Breast Oncology, Aichi Cancer Center Hospital
name: Masataka Sawaki
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hagiwara Y, Sawaki M, Uemura Y, Kawahara T, Shimozuma K, Ohashi Y, Takahashi M, Saito T, Baba S, Kobayashi K, Mukai H, Taira N. Impact of chemotherapy on cognitive functioning in older patients with HER2-positive breast cancer: a sub-study in the RESPECT trial. Breast Cancer Res Treat. 2021 Aug;188(3):675-683. doi: 10.1007/s10549-021-06253-0. Epub 2021 Jun 2.
citation: Taira N, Sawaki M, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Ohashi Y, Mukai H, Kawahara T; RESPECT Study Group. Health-Related Quality of Life With Trastuzumab Monotherapy Versus Trastuzumab Plus Standard Chemotherapy as Adjuvant Therapy in Older Patients With HER2-Positive Breast Cancer. J Clin Oncol. 2021 Aug 1;39(22):2452-2462. doi: 10.1200/JCO.20.02751. Epub 2021 Apr 9.
citation: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. doi: 10.1200/JCO.20.00184. Epub 2020 Sep 16.