STereotactic Body Radiotherapy (SBRT) for Oligoprogressive Breast Cancer

Official title

STereotactic Body Radiotherapy (SBRT) After oligoprogRession Metastatic Breast Cancer (STAR-B)

Overview

Recent advances in systemic therapy have facilitated improved progression-free survival (PFS) and treatment tolerability in metastatic breast cancer patients (MBC). Oligoprogression (OP) refers to progression limited to five or fewer sites in otherwise controlled systemic disease on a drug therapy. Stereotactic body radiotherapy (SBRT) has the potential to locally ablate resistant OP lesions that develop on a systemic treatment, and may consequently delay the need for change in drug therapy, delay time to chemotherapy and prolong PFS. This is a phase II trial of SBRT plus continuation of current systemic therapy line for OP MBC patients, to determine rate of delay of change in systemic therapy of at six months. PFS, time to chemotherapy and quality of life will also be assessed.

Interventions

• Radiation Stereotactic body radiotherapy
  Stereotactic body radiotherapy in 5 fractions (body) or 2 or 4 fractions (spine) plus continuation of first line systemic therapy

Primary outcome measures

• Percentage of patients with change in systemic therapy [Time frame: Six months]

Secondary outcome measures (5)

• Progression-free survival [Time frame: 3, 6, 12, 18, and 24 months]
• Local progression [Time frame: 3, 6, 12, 18, and 24 months]
• Time to chemotherapy [Time frame: 3, 6, 12, 18, and 24 months]
• Overall Survival [Time frame: 3, 6, 12, 18, and 24 months]
• CTCAE Toxicity [Time frame: 3, 6, 12, 18, and 24 months]

Eligibility criteria

Inclusion criteria

• Diagnosis of progressive metastatic breast cancer on first line systemic therapy, including either hormone receptor positive, Her-2 negative (HR+/Her2-) on endocrine therapy + CDK4/6 inhibitor or Her-2 positive (hormone receptor positive or negative /Her2+) on Her2-targeted therapy regimens.
• Progressive disease limited to "oligoprogression", defined as progression of 5 or fewer extra-cranial lesions with otherwise controlled systemic disease on current line of systemic therapy.
• Patients must have previously controlled disease for at least six months on current systemic therapy
• Deemed a candidate for stereotactic body radiotherapy (SBRT) to all OP lesions

Exclusion criteria

• Requires change in systemic therapy line at the time of OP as determined by medical oncologist;
• Progression on 2nd line or subsequent lines of therapy
• Lacks CT or bone scan Imaging within previous 45 days;
• Progression in >3 sites in the liver or lung;
• Hormone positive disease on endocrine therapy only at time of enrollment;
• Previous radiotherapy to same site or vicinity preventing definitive SBRT (e.g. within 5 cm);
• Lesions deemed not amenable to SBRT due to large size or location;
• Unacceptable fracture risk according to clinician judgement for bone lesions;
• Brain metastasis or Spinal cord compression;
• History of major radiosensitivity syndrome or contraindications to radiotherapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18 PMID 25524798
• Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Dieras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. doi: 10.1056/NEJMoa1607303. PMID 27959613
• Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final ana PMID 26947331
• Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, Andre F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy PMID 27717303
• Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negati PMID 29718092
• Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortes J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. PMID 32171426
• Andre F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Papai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. doi: 10.1056/NEJMoa1813904. PMID 31091374
• Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4594-60 PMID 20855825

Identifiers

NCT: NCT06489821 · STAR-B

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗