Study Assessing Stereotactic Radiotherapy in Therapeutic Strategy of Oligoprogressive Renal Cell Carcinoma Metastases (GETUG-StORM-01)

• ClinicalTrials.gov Identifier: NCT04299646
• Recruitment Status: Recruiting
• First Posted: March 9, 2020
• Last Update Posted: August 1, 2023
• Sponsor: Centre Francois Baclesse
• Collaborators: National Cancer Institute, France; GETUG
• Information provided by (Responsible Party): Centre Francois Baclesse

Study Description

Brief Summary:

Every year, 12500 primary renal cell carcinoma (RCC) are diagnosed in France. Metastases occur in half of RCC patients.

Management of metastatic RCC is based on systemic treatments (targeted therapies/immunotherapy). However, resistance to systemic treatment is frequent. In case of progression, usual therapeutic attitude is initiating another systemic therapy.

Because of the emergence of resistant tumor clonal cells, some patients progress only on few sites while the rest of tumor burden is controlled. In this setting named oligoprogressive disease [isolated progression of <3-5 metastase(s)], ablative treatments of these evolving metastatic sites could allow a disease control and a reduced risk of new metastases occurrence by tumor-cell reembolization. Such strategy is challenging to prolong ongoing systemic treatment and delay further lines.

Although RCC was considered radioresistant and radiotherapy with conventional fractionation was mainly used for palliation of symptoms, stereotactic radiotherapy (SRT), by delivering high dose in one or few fractions, allows local control for about 90% of RCC metastases through various radiobiological pathways. Furthermore, some data suggest that high-dose focal irradiation of RCC could induce a systemic antitumor response mediated by immunologic effectors(1). This phenomenon ("abscopal effect") could be enhanced in patients under immunotherapy, including anti-PD1.

Several retrospective studies and one non-randomized phase-II study highly suggest the interest of SRT as focal ablative treatment in RCC oligometastases with excellent local control rates and low toxicity(2,3).

Furthermore, the multicentric retrospective study the sponsor recently conducted within the GETUG group among 101 metastatic RCC patients with oligoprogression under systemic therapy highlighted that SRT on progressive sites provided a median of 8.6-month progression-free survival and allowed to continue current systemic line for 10.5 months.

However, to date, there are no prospective data assessing the interest of SRT for management of oligoprogressive metastatic RCC.

The sponsor aim to prospectively evaluate the interest of SRT as a therapeutic strategy for local control of oligoprogressive metastatic RCC under ongoing systemic treatment, and consequently delay subsequent systemic treatment.

Condition or disease	Intervention/treatment	Phase
Metastatic Renal Cell Carcinoma; Radiotherapy	Radiation: Steretactic radiotherapy; Drug: Pursuit of ongoing systemic treatment	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized 2:1 phase II trial
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study Assessing Stereotactic Radiotherapy in Therapeutic Strategy of Oligoprogressive Renal Cell Carcinoma Metastases
• Actual Study Start Date: July 1, 2020
• Estimated Primary Completion Date: July 2024
• Estimated Study Completion Date: January 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Steretactic radiotherapy plus systemic treatment	Radiation: Steretactic radiotherapy; Steretactic radiotherapy; Drug: Pursuit of ongoing systemic treatment; Pursuit of ongoing systemic treatment
Active Comparator: Systemic treatment	Drug: Pursuit of ongoing systemic treatment; Pursuit of ongoing systemic treatment

Outcome Measures

Primary Outcome Measures :

1. Progression-free survival [ Time Frame: 6 months post-randomization ]

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Until 1 month after end of treatment ]
2. Local control rate [ Time Frame: 3, 6 and 12 months after randomization ]
3. Overall control rate [ Time Frame: 3, 6 and 12 months after randomization ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clear cell renal cancer histologically proved (association with other histologic component are permitted)
• Patients of good or intermediate prognostic, according to Heng criteria
• Extracerebral metastatic disease documented with imagery
• Patients treated in first or second line systemic therapy
• Systemic treatment may be targeted therapies (tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors) and/or immunotherapy according to French applicable standards; patients treated in a clinical trial are also eligible if allowed by trial sponsor
• Oligoprogressive disease documented with imagery, defined as the emergence or progression of 1 to 3 metastases and progression localized in up to 2 organs
• Oligoprogressive disease confirmed with 2 CT scans performed 2 months apart
• At least one measurable progressing metastasis according to R.E.C.I.S.T. criteria v1.1
• All oligoprogressive target lesions measuring ≤ 4 cm
• Good general condition (WHO performance status ≤ 2)
• All progressive lesions have to be accessible to SRT, performed concurrently or sequentially
• No contraindication to systemic therapy and stereotactic radiation therapy
• Patients aged 18 years or older
• Signed informed consent form
• Patients affiliated to the social security system

Exclusion Criteria:

• More than 3 progressive metastases
• Non measurable disease according R.E.C.I.S.T. criteria
• Patients who received 3 or more lines of systemic therapy
• Inability to treat all progressive metastatic sites with SRT
• Previous radiation therapy performed in ≥ 1 target lesion
• At least 1 oligoprogressive target lesion measuring > 4 cm
• Presence of brain metastases
• Presence of ultra-central pulmonary metastasis
• Progressing metastasis in a long bone
• At least 1 progressive metastasis requiring surgical treatment
• Current or past history of second neoplasm diagnosed within the last 5 years
• Pregnancy or breast feeding or inadequate contraceptive measures
• Patients who cannot be adequately followed up
• Patient deprived of freedom or under guardianship

Contacts and Locations

Contacts

Contact: Emmanuel MEYER, MD; + 332 31 45 50 20; e.meyer@mail.baclesse.fr

Contact: Jean-Michel GRELLARD; +33 2 31 45 50 02; jm.grellard@baclesse.unicancer.fr

Locations

France

Clinique Claude Bernard; Not yet recruiting

Albi, France

Contact: Laurent VOTRON, MD

Principal Investigator: Laurent VOTRON, MD

Sub-Investigator: Claude ALZIEU, MD

Sub-Investigator: Pierre AUBERDIAC, MD

Sub-Investigator: Yan BERGE, MD

Institut de Cancérologie de l'Ouest; Not yet recruiting

Angers, France

Contact: Jérémy COLLIAUX, MD

Principal Investigator: Jérémy COLLIAUX, MD

Sub-Investigator: Nathalie MESGOUEZ-NEBOUT, MD

Sub-Investigator: Hadji HAMIDOU, MD

Sub-Investigator: Thibaut LIZEE, MD

Institut Bergonié; Not yet recruiting

Bordeaux, France

Contact: Pauline GILLON, MD

Principal Investigator: Pauline GILLON, MD

Radiothérapie Bordeaux Nord Aquitaine; Not yet recruiting

Bordeaux, France

Contact: Sigolène GALLAND-GIRODET, MD

Principal Investigator: Sigolène GALLAND-GIRODET, MD

Sub-Investigator: François GUICHARD, MD

Sub-Investigator: Bénédicte HENRIQUES, MD

Centre François Baclesse; Recruiting

Caen, France, 14076

Contact: Emmanuel MEYER, MD +33 2 31 45 50 20 e.meyer@mail.baclesse.fr

Contact: Jean-Michel jm.grellard@baclesse.unicancer.fr +33 2 31 45 50 02 jm.grellard@baclesse.unicancer.fr

Principal Investigator: Emmanuel MEYER, MD

Sub-Investigator: Florence JOLY, PhD

Sub-Investigator: Pierre-Emmanuel BRACHET, MD

Sub-Investigator: Elodie COQUAN, MD

Centre Jean Perrin; Not yet recruiting

Clermont-Ferrand, France

Contact: Genevieve LOOS, MD

Principal Investigator: Genevieve LOOS, MD

Sub-Investigator: Hakim MAHAMMEDI, MD

Sub-Investigator: Jessica MIROIR, MD

CHU Henri Mondor; Not yet recruiting

Créteil, France

Contact: Yacid BELKACEMI, MD

Principal Investigator: Yacid BELKACEMI, MD

Sub-Investigator: Gabriele CORAGGIO, MD

Institut de cancérologie de Bourgogne (Dijon, Auxerre, Chalon sur Saône); Not yet recruiting

Dijon, France

Contact: Alexis LEPINOY, MD

Principal Investigator: Alexis LEPINOY, MD

Sub-Investigator: Benjamin SCHIPMAN, MD

Sub-Investigator: Véronique LORGIS, MD

Sub-Investigator: Nicolas LESCUT, MD

Centre Léon Bérard; Not yet recruiting

Lyon, France

Contact: Naji SALEM, MD

Principal Investigator: Naji SALEM, MD

Sub-Investigator: Gwenaëlle GRAVIS, MD

Sub-Investigator: Cécile VICIER, MD

Sub-Investigator: Mathilde GUERIN, MD

Sub-Investigator: Slimane DERMECHE, MD

Sub-Investigator: Géraldine PIGNOT, MD

Sub-Investigator: Jochen WALZ, MD

CHU La Timone; Not yet recruiting

Marseille, France

Contact: Xavier MURACCIOLE, MD

Principal Investigator: Xavier MURACCIOLE, MD

Sub-Investigator: Eric LECHEVALLIER, MD

Sub-Investigator: Gilles KARSENTY, MD

Sub-Investigator: Jean-Laurent DEVILLE, MD

Sub-Investigator: veronique DELAPORTE, MD

ICM; Not yet recruiting

Montpellier, France

Contact: David AZRIA, PhD

Principal Investigator: David AZRIA, PhD

Sub-Investigator: Marie CHARISSOUX, MD

Sub-Investigator: Diego TOSI, MD

Sub-Investigator: Carmen LLACER-MOSCARDO, MD

Sub-Investigator: Marie VIALA, MD

Institut de Cancérologie de Lorraine; Not yet recruiting

Nancy, France

Contact: Anais STEFANI, MD

Principal Investigator: Anais STEFANI, MD

Sub-Investigator: Anne-Sophie BAUMANN, MD

Sub-Investigator: Jean-François PY, MD

Institut de Cancérologie de l'Ouest; Not yet recruiting

Nantes, France

Contact: Stephane SUPIOT, MD

Principal Investigator: Stephane SUPIOT, MD

Sub-Investigator: Valentine GUIMAS, MD

Sub-Investigator: Vincent LIBOIS, MD

Sub-Investigator: Emmanuel RIO, MD

Centre Haute Energie; Not yet recruiting

Nice, France

Contact: René Jean BENSADOUN, PhD

Principal Investigator: René Jean BENSADOUN, PhD

Institut Curie; Not yet recruiting

Paris, France

Contact: Samar Line KRHLI, MD

Principal Investigator: Samar Line KRHLI, MD

Sub-Investigator: Gilles CREHANGE, MD

Sub-Investigator: Mathieu MINSAT, MD

Sub-Investigator: Thomas FREDERIC MOREAU, MD

Institut de Cancérologie de la Loire Lucien Neuwirth; Not yet recruiting

Saint-Étienne, France

Contact: Nicolas MAGNE, MD

Principal Investigator: Nicolas MAGNE, MD

Sub-Investigator: Julien LANGRAND-ESCURE, MD

Sub-Investigator: Alexis VALLARD, MD

Sub-Investigator: Jane-Chloé TRONE, MD

Sub-Investigator: Grégoire PIGNE, MD

IUCT; Not yet recruiting

Toulouse, France

Contact: Pierre GRAFF-CAILLEAUD, MD

Principal Investigator: Pierre GRAFF-CAILLEAUD, MD

Sub-Investigator: Jonathan KHALIFA, MD

Centre marie Curie; Not yet recruiting

Valence, France

Contact: Jean-Baptiste GUY, MD

Principal Investigator: Jean-Baptiste GUY, MD

Sub-Investigator: Emilie BONNET, MD

Sub-Investigator: Bertrand FLEURY, MD

Sponsors and Collaborators

Centre Francois Baclesse

National Cancer Institute, France

GETUG

More Information

• Responsible Party: Centre Francois Baclesse
• ClinicalTrials.gov Identifier: NCT04299646
• Other Study ID Numbers: GETUG-StORM-01
• First Posted: March 9, 2020
• Last Update Posted: August 1, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases