Comparing Sequential Neoadjuvant Treatment Including Chemotherapy and Accelerated Radiation Focused to the Tumor Bed vs Neoadjuvant Chemotherapy Alone

  • STATUS
    Recruiting
  • End date
    Mar 18, 2025
  • participants needed
    362
  • sponsor
    University Hospital, Grenoble
Updated on 16 May 2021

Summary

In the NeoAPBI 01 trial, the objective is to demonstrate the efficacy of combined APBI and CT administered sequentially in patients with intermediate ad high risk BC. The hypothesis is that combined PST-sequential APBI may increase the rate of pCR, breast conservation and survival without additional toxicity, as seen with WBI

Description

Phase I:

The total APBI dose is set to level I at 20 Gy (in 10 fractions over 5 days; n=5) and then level II at 24 Gy (in 12 fractions over 6 days) delivered to the tumor using two fractions/day of 2 Gy spaced by at least 6 hours. The biological effective dose (BED) is 32 Gy and 47 Gy for alpha/beta of 10 and 3.5, respectively. As compared to the standard fractionation of 2 Gy/fraction the BED is 26.8 Gy and 30 Gy for the 2 values of alpha/beta.

In case of the impossibility to deliver two fractions/day, patients should be treated using a single fraction of 3.125 Gy/day up to 8 fractions (total dose of 25 Gy). The BED is 32.8 Gy and 47.3 Gy for alpha/beta of 10 and 3.5, respectively. As compared to the standard fractionation of 2 Gy/fraction the BED is 27.3 Gy and 30.1 Gy for the 2 values of alpha/beta.

In both schemes, 95% of the prescribed dose should be delivered in at least 90% of the PTV.

All patients who undergo BCS after the end of PST-APBI will receive postoperative WBI (+/- nodal areas) delivering a total dose of 45-50 Gy using standard fractionation (1.8 or 2 Gy) or hypofractionated schedules using > 15 fractions in 3 weeks. Technique and boost delivery will be left at the investigator's discretion and local policy. Patients who had TM should also receive PMRT if indicated delivering 45-50.4 Gy using standard fractionation (1.8 or 2 Gy). If the patient did not complete a full course of PST prior to surgery, CT will be given prior to or immediately following postoperative RT depending on the institutional protocol. Other post-operative treatments will be at the investigator's discretion. Adjuvant hormonal treatment will be administered to HR+ patients.

Phase II:

This is a phase II randomized study designed for patients with newly diagnosed intermediate and high risk non-metastatic BC who are candidates for a minimum of six cycles of PST using anthracycline and/or taxane based regimens, who desire BCS but are not eligible due to tumor/breast ratio. All patients will have a clip in the tumor bed before or after the first 1-2 cycles of PST.

Eligible patients who have consented to participate in the study will be randomized to treatment Arm A or B:

Arm A: 6-8 cycles of PST using anthracycline and/or taxane based regimens, according to their physician's preference and center policy.

Arm B: The patients will receive 3D conformal or other modality (eg IMRT, VMAT) APBI during their PST sequence. APBI will be planned sequentially between the PST cycles, 2 weeks after the 3rd/6 or the 4th/8 cycle of PST.

For the purpose of quality of the target volume definition, it is mandatory to make a planning CT-scan in treatment position before the initiation of chemotherapy. MRI or US fusion with CT scan images can increase target volume definition and should be used if necessary. For all patients, treatment planning should be made on a planning CT-scan shortly preceding the initiation of radiation therapy to take possible tumor shrinkage and breast shape changes into account.

The CTV is defined as GTV + 1cm. The margin to the PTV depends on the measurements of the center and thereby the positioning and verification techniques. If this is not known, PTV should be defined as CTV + 1 cm around. The PTV should be used for beam shaping while for dose evaluation and calculation a PTVeval will be defined as PTV excluding the skin + 5 mm and the thoracic wall (ribs and intercostal muscles). IMRT should not be used in the protocol. The PTVeval should not exceed 40% of the total breast volume.

Study Arms:

All patients must undergo surgery even in cases of clinical complete response. Surgery will be scheduled 4 to 6 weeks from the last day of PST.

Modified radical mastectomy is indicated in case of limited clinical response, or progressive disease, or if tumor size/breast size does not permit BCS. The decision should be based on US or MRI confirmation of the response. Post TM radiation therapy should be applied according to the center's guidelines. High risk patients should receive nodal radiotherapy policy.

All patients who undergo BCS after the end of PST-APBI, will receive postoperative RT. This will consist of WBI (+/- nodal areas) to a total dose of 45-50 Gy using standard fractionation (1.8 or 2 Gy) or hypofractionated schedules using > 15 fractions in 3 weeks. Technique and boost delivery will be left at the investigator's discretion and local policy. Patients who had TM should also receive PMRT, 45-50.4 Gy using standard fractionation (1.8 or 2 Gy). If the patient did not complete a full course of PST prior to surgery, CT will be given prior to or immediately following postoperative RT depending on the institutional protocol. Other post-operative treatments will be at the investigator's discretion. Adjuvant hormonal treatment will be administered to HR+ patients.

Standard protocol:

The patients randomized to the standard treatment arm will receive a minimum of 6-8 cycles of PST using an anthracycline and/or taxane based regimen. Surgery will consist of BCS or TM according to clinical response and tumor/breast volume ratio obtained after PST. After surgery, the patients will receive standard RT to the whole breast (45-50.4 Gy in 25-28 fractions) or equivalent using hypofractionated schedule > 15 fractions in 3 weeks. RT technique and the addition of boost are left to the investigator decision according to institutional protocol. Adjuvant ET will be administered to HR+ patients after the end of radiotherapy during at least 5 years.

Auxiliary translational study Tumor core biopsies for translational studies and genetic analysis will be obtained at baseline and from the resected tumor at surgery following PST +/- APBI.

This study will focus on the prediction of pCR using cell metabolism, hypoxia and angiogenesis markers (Scottish Group). Another objective is to correlate these markers with the metabolic imaging for pCR prediction (Oscar Lambret Center, France).

Details
Condition Radiation Therapy, Breast Cancer, Sequential Partial Breast Irradiation, Intermediate and High-risk Luminal and Triple Negative Breast Cancer, Radiation Therapy, Breast Cancer, Sequential Partial Breast Irradiation, Intermediate and High-risk Luminal and Triple Negative Breast Cancer, Radiation Therapy, Breast Cancer, Sequential Partial Breast Irradiation, Intermediate and High-risk Luminal and Triple Negative Breast Cancer, Radiation Therapy, Breast Cancer, Sequential Partial Breast Irradiation, Intermediate and High-risk Luminal and Triple Negative Breast Cancer, Radiation Therapy, Breast Cancer, Sequential Partial Breast Irradiation, Intermediate and High-risk Luminal and Triple Negative Breast Cancer
Treatment Chemotherapy, Accelerated Partial Breast Irradiation
Clinical Study IdentifierNCT02806258
SponsorUniversity Hospital, Grenoble
Last Modified on16 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients 18 years of age
Histologically confirmed invasive carcinoma of the breast
Patient who desires breast conservation
Tumor stage T1N1, T2-3 N0-1
Operable BC for which an indication for CT is determined, including T1N1 and high risk T2-3 N0-1 tumors
Lobular and/or ductal invasive carcinoma
Confirmation by imaging (standard +/- MRI) of unicentric and unilateral disease
Luminal B (defined by hormone receptor positive and grade II-III (if available from core biopsy) and Ki67 15% or by genomic analysis) and TNG subtypes
HER2 negative
No distant metastases
No contraindication for PST with anthracycline and/or taxane based regimens
Patients with no psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator with the aid of written information

Exclusion Criteria

Patients considered too frail for CT whatever their age
Breast cancer clinical grade T4 and /or with major nodal involvement N2 (clinically, US, MRI or PET-CT)
Lumpectomy is considered to be possible with an anticipated favourable cosmetic outcome considering the tumor size/breast size
Multicentricity that would not allow BCS as confirmed by breast imaging
Uni or bilateral inflammatory (T4d) BC
Metastatic disease
Other histology types: ciribriform or tubular or mucinous or epideroid carcinomas
Her2 positive
No signed consent to participate in the study
Previous malignancy (except non melanoma skin cancer, thyroid carcinoma, non-invasive cancers outside the breast and patients with previous cancer in remission since more > 5 years)
Patients with psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
Patients unwilling or unable to comply with the protocol (especially necessity to undergo breast surgery despite clinical complete response)
Patients who have received any other investigational drugs within 30 days prior to the screening visit
Pregnancy
Active connective tissue disease involving the skin
Patients with other concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note