Clinical trial NCT00208273: Concomitant and Sequential Radiohormonotherapy in Adjuvant Breast Cancer
Official title: A Phase II Randomized Study to Compare Skin Late Toxicities of Concomitant Letrozole-Radiotherapy and Radiotherapy Followed by Letrozole as Adjuvant Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Postmenopausal breast cancer, radiohormonotherapy sequences
ER+ and/or PgR+,
Postmenopausal Breast cancer,
Adjuvant setting
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2005-09-21
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will compare grade 2 or greater late skin toxicities of concomitant letrozole-radiotherapy and radiotherapy followed by letrozole as adjuvant therapy for postmenopausal women with receptor (estrogen receptor \[ER\] and/or progesterone receptor \[PgR\]) positive tumors. Each drug will be prescribed for 5 years.

Detailed description: This trial is an open-label randomized multicenter phase II study.

A ratio of 1 to 1 will be used for the randomization process between the two arms:

* Arm A : Letrozole 2.5 mg daily for 5 years started three weeks before the first day of adjuvant radiotherapy.
* Arm B : Letrozole 2.5 mg daily for 5 years started three weeks after the last day of adjuvant radiotherapy.

All patients will be followed every 3 months for toxicities, disease status and for survival until death.

Eligibility criteria: Inclusion Criteria:

* Compliant postmenopausal women
* Conservative breast cancer surgery
* Extension evaluation of disease will be proven negative
* Patients with tumor negative margins
* Patients will be classified as T1, T2, T3; Sentinel node negative, N0, N1 or N2; M0.
* Receptor positive tumors (ER and/or PgR = 10 fmol/mg cytosol protein; or = 10% of the tumor cells positive by immunocytochemical evaluation).
* Adequate marrow function (polynuclear neutrophils \>= 1200.10\^9/l, platelets \>= 100.10\^9/l, and hemoglobin \>= 10 g/dl).
* Hepatic function (bilirubin \>= 30 µmol/l, ALT (SGPT) or AST (SGOT) \>= 1.5 x upper limit of the institution) and cholesterol level \<2 x upper limit of the institution.
* Must be geographically accessible for follow-up.
* Written and dated informed consent

Exclusion Criteria:

* Patients with distant metastases.
* Bilateral breast cancer (concomitant or prior) except in situ lesion, either ductal or lobular, of the contralateral breast.
* Patients staged T4 or N3 or treated by not conservative surgery (radical mastectomy).
* Patients with neoadjuvant chemotherapy or hormonal therapy.
* Patients with previous or concomitant other (not breast cancer) malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years.
* Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.
* Patients treated with systemic investigational drugs within the past 30 days.
* Breast cancer chemoprevention with anti-estrogens
* Hormone replacement therapy (HRT) not stopped at least 4 weeks before randomization
* Patients known to be HIV positive (no specific tests are required to determine the eligibility).

Primary outcomes:
measure: Sub-cutaneous late toxicity
timeFrame: 2 years
Secondary outcomes:
measure: Early toxicity
measure: Lung late toxicity
measure: Cosmetic results
measure: Local failure
measure: Relapse-free survival
measure: Overall survival
Other outcomes:
Locations:
city: Montpellier
country: France
facility: CRLC Val d'Aurelle
Study officials:
affiliation: CRLC Val d'Aurelle
name: David AZRIA, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Azria D, Pelegrin A, Dubois JB, Mirimanoff RO, Ozsahin M. Radiation therapy and tamoxifen: concurrent or sequential? It's no longer the question! J Clin Oncol. 2005 Jun 20;23(18):4239-41; author reply 4241-2. doi: 10.1200/JCO.2004.00.8623. No abstract available.
citation: Azria D, Larbouret C, Cunat S, Ozsahin M, Gourgou S, Martineau P, Evans DB, Romieu G, Pujol P, Pelegrin A. Letrozole sensitizes breast cancer cells to ionizing radiation. Breast Cancer Res. 2005;7(1):R156-63. doi: 10.1186/bcr969. Epub 2004 Dec 7.
citation: Azria D, Gourgou S, Sozzi WJ, Zouhair A, Mirimanoff RO, Kramar A, Lemanski C, Dubois JB, Romieu G, Pelegrin A, Ozsahin M. Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients. Br J Cancer. 2004 Oct 4;91(7):1251-60. doi: 10.1038/sj.bjc.6602146.
citation: Azria D, Lemanski C, Zouhair A, Gutowski M, Belkacemi Y, Dubois JB, Romieu G, Ozsahin M. [Adjuvant treatment of breast cancer by concomitant hormonotherapy and radiotherapy: state of the art]. Cancer Radiother. 2004 Jun;8(3):188-96. doi: 10.1016/j.canrad.2004.01.003. French.
citation: Bourgier C, Kerns S, Gourgou S, Lemanski C, Gutowski M, Fenoglietto P, Romieu G, Crompton N, Lacombe J, Pelegrin A, Ozsahin M, Rosenstein B, Azria D. Concurrent or sequential letrozole with adjuvant breast radiotherapy: final results of the CO-HO-RT phase II randomized trial. Ann Oncol. 2016 Mar;27(3):474-80. doi: 10.1093/annonc/mdv602. Epub 2015 Dec 17.
citation: Azria D, Belkacemi Y, Romieu G, Gourgou S, Gutowski M, Zaman K, Moscardo CL, Lemanski C, Coelho M, Rosenstein B, Fenoglietto P, Crompton NE, Ozsahin M. Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial. Lancet Oncol. 2010 Mar;11(3):258-65. doi: 10.1016/S1470-2045(10)70013-9. Epub 2010 Feb 6.