Clinical trial NCT04299646: A Phase II Study Assessing Stereotactic Radiotherapy in Therapeutic Strategy of Oligoprogressive Renal Cell Carcinoma Metastases
Official title: A Phase II Study Assessing Stereotactic Radiotherapy in Therapeutic Strategy of Oligoprogressive Renal Cell Carcinoma Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Radiotherapy
Lead sponsor: Centre Francois Baclesse
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
name: GETUG
First posted: 2020-03-09
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non randomized phase II trial
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression-free survival
timeFrame: 6 months post-randomization
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Until 1 month after end of treatment
measure: Local control rate
timeFrame: 3, 6 and 12 months after randomization
measure: Overall control rate
timeFrame: 3, 6 and 12 months after randomization
Other outcomes:
Locations:
city: Albi
country: France
facility: Clinique Claude Bernard
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Radiothérapie Bordeaux Nord Aquitaine
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Créteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: Centre Georges François LECLERC
city: Dijon
country: France
facility: Institut de cancérologie de Bourgogne (Dijon, Auxerre, Chalon sur Saône)
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Havre
country: France
facility: Centre de radiothérapie Guillaume le Conquérant
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: CHU La Timone
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Metz
country: France
facility: CHR
city: Montpellier
country: France
facility: ICM
city: Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: Centre Haute Energie
city: Nîmes
country: France
facility: CHU
city: Paris
country: France
facility: Institut Curie
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Rouen
country: France
facility: CHU
city: Saint-Étienne
country: France
facility: Institut de Cancérologie de la Loire Lucien Neuwirth
city: Toulouse
country: France
facility: IUCT
city: Valence
country: France
facility: Centre marie Curie
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References: