"A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients with 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer with Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer.” RXPONDER

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Grupo Espanol De Investigacion En Cancer De Mama

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Sep 2012 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515368-29-00

EudraCT number

2012-000174-37

ClinicalTrials.gov

NCT01272037

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the effect of chemotherapy in patients with node positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype DX®. In patients with 1-3 positive nodes, and hormone receptor (HR)-positive, HER2-negative breast cancer with RS ≤ 25 treated with endocrine therapy we will test whether the difference in disease-free survival for patients treated with chemotherapy compared to no chemotherapy depends directly on the magnitude of RS. If benefit depends on the RS score, the trial will determine the optimal cutpoint for recommending chemotherapy or not.

Secondary objectives 7

1. To compare overall survival (OS), distant disease-free survival (DDFS) and local disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
2. To compare the toxicity across the treatment arms.
3. To perform other molecular assays or test other signatures that measure prognosis and potential benefit of chemotherapy and compare them to Oncotype DX®
4. To determine the role of other assays as predictors of DFS, DDFS and LDFI for patients randomized to chemotherapy versus no chemotherapy.
5. To determine the impact of treatment with chemotherapy versus no chemotherapy on patient-reported fatigue and cognitive concerns (secondary HRQL outcomes)
6. To determine the impact of management with Oncotype DX® on patient-reported decision conflict, perceptions regarding Oncotype DX® testing, and survivor concerns prior to screening, after disclosure of test results, and during the randomized trial (secondary HRQL outcomes).
7. The presence of circulating tumor cells (CTC+) using two CTC platforms will be assessed at up to two time points to assess late recurrence in those still at risk for the primary outcome. Invasive disease-free survival (IDFS) will be compared between CTC+ versus CTC-, incorporating use of endocrine therapy

Conditions and MedDRA coding

patients with node positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype DX®

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2
2. Patients with multifocal, multicentric and synchronous bilateral breast cancers are allowed
3. Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph nodes dissection (ALND).
4. Patients must not have inflammatory breast cancer and must not have metastatic disease. Patients with a prior diagnosis of DCIS are eligible if they received mastectomy alone (no therapeutic radiation, intraoperative radiation or endocrine therapy). Radiation in the opposite breast is acceptable. Partial breast irradiation (including brachytherapy) is not allowed.
5. Patients must have had either breast-conserving surgery with planned radiation therapy or total mastectomy (with or without planned postmastectomy radiation). Patients must have clear margins (as per local institutional guidelines).
6. Registration of patients who have not yet undergone Oncotype DX® screening must occur no later than 56 days after definitive surgery. (For all patients, Step 2 Registration must occur within 84 days after definitive surgery.) If the Oncotype DX® Recurrence Score is already known and is 25 or less, the patient must be registered to Step 2 immediately following Step 1 registration. If the Oncotype DX® Recurrence Score is already known and is greater than 25, the patient is ineligible.
7. Patients must be females > or = 18 years of age. As the Oncotype DX® Recurrence Score has not been validated in men with breast cancer, men are not eligible for this study
8. Patients must have a complete history and physical examination within 28 days prior to registration
9. Patients must have a performance status of 0-2 by Zubrod criteria
10. Patients must be able to receive taxane and/or anthracycline based chemotherapy.
11. Patients must not have begun chemotherapy or endocrine therapy for their breast cancer prior to registration.
12. Patients must not require chronic treatment with systemic steroids (inhaled steroids are allowed) or other immunosuppressive agents
13. Patients must not have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registration.
14. Patients must not be pregnant or nursing due to the possibility of harm to a fetus or nursing infant from this treatment regimen. Women of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of ?reproductive potential? if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
15. No other prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years
16. The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12. Patients who consented to QOL prior to 12/1/12 should continue to complete QOL forms per their expectation report.
17. All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion criteria 2

1. Patients must not have inflammatory breast cancer and must not have metastatic disease. Patients with a prior diagnosis of DCIS are eligible if they received mastectomy alone (no therapeutic radiation or endocrine therapy). Radiation in the opposite breast is acceptable. Partial breast irradiation (including brachytherapy) is not allowed
2. Patients must not have begun chemotherapy or endocrine therapy for their breast cancer prior to registration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Invasive Recurrence

Secondary endpoints 4

1. Invasive Disease-Free Survival
2. Distant Disease-Free Survival
3. Local Disease-Free Interval.
4. Overall Survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Grupo Espanol De Investigacion En Cancer De Mama

Sponsor organisation

Fundacion Grupo Espanol De Investigacion En Cancer De Mama

Address

Avenida De Los Pirineos 7 Oficina 1-14, Industrial Zona Sur Industrial Zona Sur

City

San Sebastian De Los Reyes

Postcode

28703

Country

Spain

Scientific contact point

Organisation

Fundacion Grupo Espanol De Investigacion En Cancer De Mama

Contact name

Clinical Operations Department

Public contact point

Organisation

Fundacion Grupo Espanol De Investigacion En Cancer De Mama

Contact name

Clinical Operations Department

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications