Clinical trial NCT03616626: Whole Breast Irradiation vs Twice Daily vs. Once Daily Accelerated Partial Breast Irradiation
Official title: Phase III Randomized Study of Adjuvant Whole Breast Versus Partial Breast Irradiation Using Once Daily or Twice Daily Fractionation Scheme in Women With Stage I or II Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Radiation Toxicity
Keywords: Breast Cancer
Accelerated partial Breast Irradiation
Breast cosmesis
radiation Toxicity
Lead sponsor: National Cancer Institute, Egypt
Sponsor class: OTHER
First posted: 2018-08-06
Enrollment: 91
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized phase III trial in women with invasive carcinoma of the breast with negative axillary nodes treated by Breast Conserving Surgery (BCS). Eligible, patients will be randomly allocated to receive radiotherapy of 3 Dimensional Conformal Radiation Therapy (3DCRT) Whole Breast Irradiation (WBI) 50 Gray (Gy) in 25 daily fractions over 5 weeks or Accelerated Partial Breast Irradiation (APBI) 38.5 Gy in 10 daily fractions of 3.85Gy over two weeks or 38.5 Gy in 10 twice daily fractions of 3.85Gy over one week. Patients will be followed at 6, 12, 18 and 24 months post randomization. Cosmetic outcome will be measured using photographs and evaluated by a panel of trained radiation oncologists. Radiation toxicity will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

Detailed description: Women with invasive carcinoma of the breast less than 3 cm with negative axillary nodes , following BCS, who meet the inclusion criteria will be approached for potential study enrollment.

Eligible, consenting patients will be randomly allocated to receive radiotherapy of 3DCRT WBI 50 Gy in 25 fractions over 5 weeks or APBI 38.5 Gy in 10 once daily fractions of 3.85Gy over two weeks or 38.5 Gy in 10 twice daily fractions of 3.85 Gy over one week. Patients will be followed at 6, 12, 18 and 24 months post randomization. Cosmetic outcome will be measured using photographs and evaluated by a panel of trained radiation oncologists using the EORTC Breast Cosmetic Rating System. Radiation toxicity will be assessed using the NCI CTCAE version 4.0. The primary outcome is to compare the acute, late toxicities and adverse cosmetic outcomes at 6, 12 and 18 months among the three groups.

Eligibility criteria: Inclusion Criteria:

Tumor characteristics

* Histologically confirmed invasive adenocarcinoma of the breast
* Tumors must be ≤ 3 cm. Gross disease must be unifocal. Negative lymph nodes
* Hormone receptor status:

Estrogen receptor (ER) status known Progesterone status known if ER analysis is negative Marginal or borderline results are considered positive Surgery

* Tumor removed with conservative breast surgery with adequate margin
* Re-excision of surgical margins allowed
* No prior breast implants
* Prior axillary staging required for patients including 1 of the following:

  * Sentinel node biopsy alone (if sentinel node is negative)
  * Sentinel node biopsy followed by axillary dissection if sentinel node is positive)
  * Axillary dissection alone with ≥ 6 axillary nodes
* Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast reference volume ≤ 30% based on postoperative pre-randomization CT scan
* Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging procedure) within the past 42 days
* No prior biologic therapy for this malignancy Chemotherapy
* No prior chemotherapy for this malignancy
* No concurrent chemotherapy during study radiotherapy Endocrine therapy
* No prior hormonal therapy for this malignancy
* Concurrent hormonal therapy allowed provided it is not administered during chemotherapy
* No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating drugs
* No concurrent hormone replacement therapy Radiotherapy
* No prior radiotherapy for this malignancy
* No prior breast or thoracic radiotherapy
* No concurrent regional nodal irradiation Other
* No other concurrent anticancer therapy Menopausal status
* Premenopausal or postmenopausal Performance status
* WHO 0-1 Other
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective non-hormonal contraception

Exclusion Criteria:

* Multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm.
* Non-epithelial breast malignancies (e.g., sarcoma or lymphoma).
* Positive axillary nodes.
* Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor.
* Suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast unless biopsied and found to be benign
* Paget's disease of the nipple
* Previous history of invasive breast cancer or DCIS.
* Synchronous bilateral invasive or non-invasive breast cancer
* Collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma), specifically dermatomyositis with a CPK level above normal, or active skin rash
* Psychiatric or addictive disorder that would preclude study therapy

Primary outcomes:
measure: Change in the Adverse cosmetic outcome using the EORTC Breast Cosmetic Rating System
timeFrame: prior to radiation, 6,12 and 18 months after radiation
Secondary outcomes:
measure: Ipsilateral Breast Tumor Recurrence (IBTR)
timeFrame: throughout the study up to 5 years
measure: Disease Free Survival
timeFrame: throughout the study up to 5 years
measure: Overall Survival
timeFrame: From date of randomization until the date of death up to 5 years
measure: Radiation Induced Early and late toxicities
timeFrame: during radiation and at 6, 12 and 18 months after radiation
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Cancer Institute
Study officials:
affiliation: Radiation Oncology Department, National Cancer Institute, Cairo University
name: Rimoun Boutrus, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hepel JT, Tokita M, MacAusland SG, Evans SB, Hiatt JR, Price LL, DiPetrillo T, Wazer DE. Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1290-6. doi: 10.1016/j.ijrobp.2009.01.009. Epub 2009 Apr 22.
citation: Jagsi R, Ben-David MA, Moran JM, Marsh RB, Griffith KA, Hayman JA, Pierce LJ. Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation. Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):71-8. doi: 10.1016/j.ijrobp.2009.01.041.
citation: Vicini F, Winter K, Wong J, Pass H, Rabinovitch R, Chafe S, Arthur D, Petersen I, White J, McCormick B. Initial efficacy results of RTOG 0319: three-dimensional conformal radiation therapy (3D-CRT) confined to the region of the lumpectomy cavity for stage I/ II breast carcinoma. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):1120-7. doi: 10.1016/j.ijrobp.2009.06.067. Epub 2009 Nov 10.
citation: Chen PY, Wallace M, Mitchell C, Grills I, Kestin L, Fowler A, Martinez A, Vicini F. Four-year efficacy, cosmesis, and toxicity using three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):991-7. doi: 10.1016/j.ijrobp.2009.03.012. Epub 2009 Jun 8.
citation: Goyal S, Daroui P, Khan AJ, Kearney T, Kirstein L, Haffty BG. Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT). Cancer Med. 2013 Dec;2(6):964-71. doi: 10.1002/cam4.157. Epub 2013 Oct 31.
citation: DE Paula U, D'Angelillo RM, Barbara R, Caruso C, Gomellini S, Caccavari A, Costarelli L, Scavina P, Mauri M, Santini E, Antonaci A, Cavaliere F, LA Pinta M, Loreti A, Fortunato L. Once Daily Accelerated Partial Breast Irradiation: Preliminary Results with Helical Tomotherapy(R). Anticancer Res. 2016 Jun;36(6):3035-9.
citation: Bentzen SM, Yarnold JR. Reports of unexpected late side effects of accelerated partial breast irradiation--radiobiological considerations. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):969-73. doi: 10.1016/j.ijrobp.2010.01.059. No abstract available.