A Dose-escalation Trial of Stereotactic Ablative Body Radiotherapy for Non-spine Bone & Lymph Node Oligometastates

NCT03486431 | Completed

• 1 other identifier: CTOR17007GZA
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Stereotactic ablative body radiotherapy (SABR) can be considered for patients with so-called "oligometastatic" disease. However, since this is a relatively new technique, information on the optimal scheduling is lacking. Even prospective randomized trials on SABR for oligometastases typically allow different fractionation schedules to be used. This is especially true for non-spine bone and lymph node metastases, where the literature is scarce to non-existent. There is also emerging evidence that SABR can stimulate the immune response, by a variety of mechanisms such as increasing TLR4 expression on dendritic cells, increasing priming of T cells in draining lymph nodes, and increasing tumor cell antigen presentation by dendritic cells. Again, it is not clear which fractionation schedule elicits the most robust immune response. Therefore, it is opportune to compare the most commonly used stereotactic regimens regarding toxicity, efficacy, and immune priming. This trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node oligometastases (≤ 3 lesions). The metastatic lesion(s) must be visible on CT and \< 5 cm in largest diameter. A total of ninety patients will be consecutively included in three different fractionation regimens. They will be offered stereotactic ablative radiotherapy to all metastatic lesions in 5, 3 or 1 fractions. Dose-limiting toxicity (DLT), defined as any acute grade 3 or 4 toxicity, will be recorded as the primary endpoint. Overall acute and late toxicity, quality of life, local control, and progression-free survival are secondary endpoints. Liquid biopsies will be collected throughout the course of this trial, i.e. at simulation, after each fraction and at 6 months after the end of the radiotherapy. Translational research will focus on assessment of circulating cytokines and flow cytometry analysis of immune cells.

Conditions

Metastatic Cancer

Keywords

Stereotactic Ablative Body Radiotherapy (SABR)

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicity

  To determine the maximum tolerated dose (MTD). The maximal tolerated dose will be defined as the dose level below which at least 10 patients present with a dose-limiting toxicity .

  6 months after SABR

Secondary Outcomes (4)

• Acute toxicities following SABR

  at 3 and 6 months after last day of SABR

• Late toxicities following SABR

  at 9, 12, 18 and 24months after last day of SABR

• Local control

  at 6 months after last day of SABR

• Progression-free survival

  at 6 months after last day of SABR

Study Arms (3)

Level I

EXPERIMENTAL

5 x 7 Gy SABR

Radiation: Stereotactic Ablative Radiotherapy (SABR)

Level II

EXPERIMENTAL

3 x 10 Gy SABR

Radiation: Stereotactic Ablative Radiotherapy (SABR)

Level III

EXPERIMENTAL

1 x 20 Gy SABR

Radiation: Stereotactic Ablative Radiotherapy (SABR)

Interventions

Stereotactic Ablative Radiotherapy (SABR) RADIATION

A minimum of thirty patients will be included for each dose level. An interval of at least 24 weeks from the first patient treatment to the next patient treatment at each dose level will be respected. In the meantime, more patients will be included in the previous dose level, in an effort to establish the secondary endpoints. In case 1-5 patients present with dose-limiting toxicity (DLT) at 6 months after SABR, thirty additional patients will be included at the same dose level. The maximal tolerated dose will be defined as the dose level below which at least 10 patients present with a dose-limiting toxicity at 6 months after SABR.

Level I; Level II; Level III

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years old with histologically confirmed malignancy.
• Patients with radiosensitive malignancy (e.g. breast, prostate,…) and oligometastases (i.e. ≤ 3 metastases) OR patients with radioresistant malignancy (e.g. renal cell carcinoma, melanoma,…) and an unlimited number of metastases.
• Metastatic lesion must be visible on CT and \< 5 cm in largest diameter.
• Patients with ECOG performance status ≤ 1.
• Patients who have received the information sheet and signed the informed consent form.
• Patients must be willing to comply with scheduled visits, treatment plan, and other study procedures.
• Patients with a public health insurance coverage.

You may not qualify if:

• Patients with life expectancy \< 6 months.
• Patients with previous radiotherapy to the metastatic area excluding stereotactic re-irradiation to the required dose level.
• Patients with significantly altered mental status or with psychological, familial, sociological or geographical condition potential hampering compliance with the study.
• Individual deprived of liberty or placed under guardianship.

Sponsors & Collaborators

• Cancer Research Antwerp: lead

Study Sites (1)

GZA St Augustinus

Wilrijk, Antwerp, 2610, Belgium

Location

Related Publications (15)

• Corbin KS, Hellman S, Weichselbaum RR. Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy. J Clin Oncol. 2013 Apr 10;31(11):1384-90. doi: 10.1200/JCO.2012.45.9651. Epub 2013 Mar 4. No abstract available.

  PMID: 23460715 BACKGROUND

• Tree AC, Khoo VS, Eeles RA, Ahmed M, Dearnaley DP, Hawkins MA, Huddart RA, Nutting CM, Ostler PJ, van As NJ. Stereotactic body radiotherapy for oligometastases. Lancet Oncol. 2013 Jan;14(1):e28-37. doi: 10.1016/S1470-2045(12)70510-7.

  PMID: 23276369 BACKGROUND

• Palma DA, Haasbeek CJ, Rodrigues GB, Dahele M, Lock M, Yaremko B, Olson R, Liu M, Panarotto J, Griffioen GH, Gaede S, Slotman B, Senan S. Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): study protocol for a randomized phase II trial. BMC Cancer. 2012 Jul 23;12:305. doi: 10.1186/1471-2407-12-305.

  PMID: 22823994 BACKGROUND

• Alongi F, Arcangeli S, Filippi AR, Ricardi U, Scorsetti M. Review and uses of stereotactic body radiation therapy for oligometastases. Oncologist. 2012;17(8):1100-7. doi: 10.1634/theoncologist.2012-0092. Epub 2012 Jun 20.

  PMID: 22723509 BACKGROUND

• Owen D, Laack NN, Mayo CS, Garces YI, Park SS, Bauer HJ, Nelson K, Miller RW, Brown PD, Olivier KR. Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases. Pract Radiat Oncol. 2014 Mar-Apr;4(2):e143-e149. doi: 10.1016/j.prro.2013.05.006. Epub 2013 Jun 29.

  PMID: 24890360 BACKGROUND

• de la Cruz-Merino L, Illescas-Vacas A, Grueso-Lopez A, Barco-Sanchez A, Miguez-Sanchez C; Cancer Immunotherapies Spanish Group (GETICA). Radiation for Awakening the Dormant Immune System, a Promising Challenge to be Explored. Front Immunol. 2014 Mar 14;5:102. doi: 10.3389/fimmu.2014.00102. eCollection 2014.

  PMID: 24672524 BACKGROUND

• Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25.

  PMID: 19706802 BACKGROUND

• Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S, Papiez L, Purdie T, Sadagopan R, Schell MC, Salter B, Schlesinger DJ, Shiu AS, Solberg T, Song DY, Stieber V, Timmerman R, Tome WA, Verellen D, Wang L, Yin FF. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010 Aug;37(8):4078-101. doi: 10.1118/1.3438081.

  PMID: 20879569 BACKGROUND

• Martin OA, Anderson RL, Russell PA, Cox RA, Ivashkevich A, Swierczak A, Doherty JP, Jacobs DH, Smith J, Siva S, Daly PE, Ball DL, Martin RF, MacManus MP. Mobilization of viable tumor cells into the circulation during radiation therapy. Int J Radiat Oncol Biol Phys. 2014 Feb 1;88(2):395-403. doi: 10.1016/j.ijrobp.2013.10.033. Epub 2013 Dec 5.

  PMID: 24315565 BACKGROUND

• Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017 Jun 9;8:15618. doi: 10.1038/ncomms15618.

  PMID: 28598415 BACKGROUND

• de Jager W, Bourcier K, Rijkers GT, Prakken BJ, Seyfert-Margolis V. Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays. BMC Immunol. 2009 Sep 28;10:52. doi: 10.1186/1471-2172-10-52.

  PMID: 19785746 BACKGROUND

• Li J, Dittmar RL, Xia S, Zhang H, Du M, Huang CC, Druliner BR, Boardman L, Wang L. Cell-free DNA copy number variations in plasma from colorectal cancer patients. Mol Oncol. 2017 Aug;11(8):1099-1111. doi: 10.1002/1878-0261.12077. Epub 2017 Jun 6.

  PMID: 28504856 BACKGROUND

• Chevolet I, Speeckaert R, Schreuer M, Neyns B, Krysko O, Bachert C, Van Gele M, van Geel N, Brochez L. Clinical significance of plasmacytoid dendritic cells and myeloid-derived suppressor cells in melanoma. J Transl Med. 2015 Jan 16;13:9. doi: 10.1186/s12967-014-0376-x.

  PMID: 25592374 BACKGROUND

• Mercier C, Claessens M, Buys MSc A, Gryshkevych S, Billiet C, Joye I, Van Laere S, Vermeulen P, Meijnders P, Lofman F, Poortmans P, Dirix L, Verellen D, Dirix P. Stereotactic Ablative Radiation Therapy to All Lesions in Patients With Oligometastatic Cancers: A Phase 1 Dose-Escalation Trial. Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1195-1205. doi: 10.1016/j.ijrobp.2020.11.066. Epub 2020 Dec 8.

  PMID: 33307151 DERIVED

• Mercier C, Dirix P, Meijnders P, Vermeulen P, Van Laere S, Debois H, Huget P, Verellen D. A phase I dose-escalation trial of stereotactic ablative body radiotherapy for non-spine bone and lymph node metastases (DESTROY-trial). Radiat Oncol. 2018 Aug 20;13(1):152. doi: 10.1186/s13014-018-1096-9.

  PMID: 30126440 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Piet Dirix, MD

  Cancer Research Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation Oncologist

Model Details: 3+3 phase I trial design

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: April 3, 2018
• Study Start: July 5, 2017
• Primary Completion: June 30, 2019
• Study Completion: December 31, 2019
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

BE (1)