IMPACTE-01: Impact of Adjuvant Radiotherapy Fractionation in Carcinomas of the Skin in Older Patients

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05794035

Collaborator

(none)

303

Enrollment

Arms

58.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Non-melanoma skin cancer (NMSC) incidence as well as morbidity rates are high in older patients. Surgery is the standard of care. About 5 to 10% of NMSC present high-risk clinico-pathologic features that can increase risk of local recurrence (LR).

Adjuvant radiation therapy (ART) is often discussed regarding the risk of local recurrence. Despite the lack of high level evidence, ART is indicated in patients according to unfavorable prognostic factors. ART benefit is generally questioned in regard to the potential degradation of the patient's quality of life (QoL). Currently there is no prospective trial or recommendations that take into account geriatric patients' evaluation and profiles during the management of NMSC. In addition, there is no data that could help to define the subgroup of elderly patients who will benefit from ART in tumors with unfavorable prognostic factors.

In terms of ART, multiple fractionation schedules are available, ranging from standard fractionation (45-60Gy in 5-6 weeks) to the extreme hypofractionation (HF) delivering 16-18Gy in one fraction.

In routine practice, HF is mainly preferred in elderly patients for more convenience by reducing the number of transports and increase health related quality of life (HRQoL). However, there is no data on the fragility profiles of these patients, nor validating any HF schedule in terms of efficacy, acute toxicity, cosmetic results, and impact on HRQoL.

the main ain objective is to evaluate the comparative efficacy of two modalities of Radiotherapy over surgery alone on local tumor control in older patients with Non Melanoma Skin Cancer (NMSC) In current practice, adjuvant radiotherapy is discussed regarding the risk of local recurrence as determined by the existence (or not) of unfavorable prognostic factors. The proposed study will include R0-high risk of CBC and CEC of the skin in elderly patients. There is no risk regarding the design of the trial as the last will respond to two important unknown questions regarding the utility of RT and its fractionation in this population. Moreover, it is an excellent opportunity to collect prospectively geriatric evaluation and HRQoL data that are lacking in the literature for skin cancers. No constraints are seen neither in the design, nor in the potential recruitments.

Condition or Disease	Intervention/Treatment	Phase
Skin Cancer, Non-Melanoma	Other: Surgery with additional moderate hypofractionation RT (15 fractions) Other: Surgery alone, without radiation post surgery Radiation: Surgery with extreme hypo fractionation treatment (HF)	N/A

Detailed Description

A short description, 5000 characters

Intro:

In terms of ART, multiple fractionation schedules are available, ranging from standard fractionation (45-60Gy in 5-6 weeks) to the extreme hypofractionation (HF) delivering 16-18Gy in one fraction.

Hypothesis/Objective

Main Objective:

To evaluate the comparative efficacy of two modalities of Radiotherapy over surgery alone on local tumor control in older patients with Non Melanoma Skin Cancer (NMSC) In current practice, adjuvant radiotherapy is discussed regarding the risk of local recurrence as determined by the existence (or not) of unfavorable prognostic factors. The proposed study will include R0-high risk of CBC and CEC of the skin in elderly patients. There is no risk regarding the design of the trial as the last will respond to two important unknown questions regarding the utility of RT and its fractionation in this population. Moreover, it is an excellent opportunity to collect prospectively geriatric evaluation and HRQoL data that are lacking in the literature for skin cancers. No constraints are seen neither in the design, nor in the potential recruitments.

Primary endpoint:

Local tumor control at 3-year follow-up in a time-to-event analysis Method This is a multicenter, randomized, open-labeled, comparative 3 arms phase III trial.

After inclusion of patient aged ≥ 70 years with performance status OMS 0-3 who had completed surgery (R0) for SCC and BCC with at least one unfavorable prognostic factor, all patientsst will have G8 score and a Geriatric Core Data Set (G CODE) evaluation. Performance of a complete oncogeriatric evaluation and its modalities will be left to the discretion of the investigator.

The patients will be randomized in 3 arms with stratification by center, time from surgery to wound healing and perineural invasion.

Arm A: Surgery alone
Arm B: Surgery + Moderate HF 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed.
Arm C: Surgery + Extreme HF : 30Gy in 5 fractions of 6Gy, 1 fraction per week, over 5 weeks to the operative bed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

303 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

After inclusion of patient aged ≥ 70 years with performance status OMS 0-3 who had completed surgery (R0) for SCC and BCC with at least one unfavorable prognostic factor, the patients will be randomized in 3 arms with stratification by center, time from surgery to wound healing and perineural invasion. Arm A: Surgery alone Arm B: Surgery + Moderate HF 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed. Arm C: Surgery + Extreme HF : 30Gy in 5 fractions of 6Gy, 1 fraction per week, over 5 weeks to the operative bed.After inclusion of patient aged ≥ 70 years with performance status OMS 0-3 who had completed surgery (R0) for SCC and BCC with at least one unfavorable prognostic factor, the patients will be randomized in 3 arms with stratification by center, time from surgery to wound healing and perineural invasion. Arm A: Surgery alone Arm B: Surgery + Moderate HF 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed. Arm C: Surgery + Extreme HF : 30Gy in 5 fractions of 6Gy, 1 fraction per week, over 5 weeks to the operative bed.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact of Adjuvant Radiotherapy Fractionation in Carcinomas of the Skin in Older Patients IMPACTE-01

Anticipated Study Start Date :

Apr 15, 2023

Anticipated Primary Completion Date :

Mar 1, 2028

Anticipated Study Completion Date :

Mar 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Surgery alone After inclusion of patient aged ≥ 70 years with performance status OMS 0-3 who had completed surgery (R0) for SCC and BCC with at least one unfavorable prognostic factor, patient will have surgery alone with no hypo fractionation treatment	Other: Surgery alone, without radiation post surgery Arm A: Surgery alone followed by surveillance
Experimental: Surgery + Moderate hypo fractionation (HF) Surgery + Moderate hypo fractionation (HF) 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed.	Other: Surgery with additional moderate hypofractionation RT (15 fractions) After randomization, patients will then be followed-up at 3 months post randomization and at each surveillance visit (M6, M12, M24 and M36). Adjuvant Radiotherapy: -Arm B: Surgery followed by moderate hypofractionation RT (15 fractions): 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed. Other Names: Arm B:
Experimental: Surgery + Extreme hypo fractionation (HF) Surgery + Extreme hypo fractionation (HF): 30Gy in 5 fractions of 6Gy, 1 fraction per week, over 5 weeks to the operative bed.	Radiation: Surgery with extreme hypo fractionation treatment (HF) After randomization, patients will then be followed-up at 3 months post randomization and at each surveillance visit (M6, M12, M24 and M36). Adjuvant Radiotherapy: -Arm C= Surgery followed by extreme hypofractionation RT (5 fractions, 2 fractions/week): 30Gy in 5 fractions of 6Gy over 5 weeks to the operative bed. Other Names: Arm C

Arm

Intervention/Treatment

Active Comparator: Surgery alone

After inclusion of patient aged ≥ 70 years with performance status OMS 0-3 who had completed surgery (R0) for SCC and BCC with at least one unfavorable prognostic factor, patient will have surgery alone with no hypo fractionation treatment

Other: Surgery alone, without radiation post surgery

Arm A: Surgery alone followed by surveillance

Experimental: Surgery + Moderate hypo fractionation (HF)

Surgery + Moderate hypo fractionation (HF) 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed.

Other: Surgery with additional moderate hypofractionation RT (15 fractions)

After randomization, patients will then be followed-up at 3 months post randomization and at each surveillance visit (M6, M12, M24 and M36). Adjuvant Radiotherapy: -Arm B: Surgery followed by moderate hypofractionation RT (15 fractions): 45Gy in 15 fractions, 3 fractions per week over 5 weeks to the operative bed.

Other Names:

Arm B:

Experimental: Surgery + Extreme hypo fractionation (HF)

Surgery + Extreme hypo fractionation (HF): 30Gy in 5 fractions of 6Gy, 1 fraction per week, over 5 weeks to the operative bed.

Radiation: Surgery with extreme hypo fractionation treatment (HF)

After randomization, patients will then be followed-up at 3 months post randomization and at each surveillance visit (M6, M12, M24 and M36). Adjuvant Radiotherapy: -Arm C= Surgery followed by extreme hypofractionation RT (5 fractions, 2 fractions/week): 30Gy in 5 fractions of 6Gy over 5 weeks to the operative bed.

Other Names:

Arm C

Outcome Measures

Primary Outcome Measures

Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [at 3 years]
Levels and changes from baseline in HRQoL as assessed by the cancer-specific European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and QLQ-ELD14 module developed for older patients with cancer, and treatment burden, as assessed by an adapted version of the Treatment Burden Questionnaire (TBQ; EVALUATION AT
QLQ-ELD14 Questionnaire [at 3 years]
Levels and changes from baseline in HRQoL as assessed by the cancer-specific European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and QLQ-ELD14 module developed for older patients with cancer, and treatment burden, as assessed by an adapted version of the Treatment Burden Questionnaire (TBQ; EVALUATION AT
rate of Toxicity [during RadiotherapyT]
Acute and late toxicity, as assessed by CTCAE v4.03 criteria
efficacy of treatment modalities on regional recurrence (RR), at 3-year follow-up [at 3 years]
progression-free survival (PFS) [at 3-year follow-up]
overall survival (OS) [at 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged ≥ 70 years
OMS 0-3
Pathology confirmation of invasive SCC or BCC
At least one of high-risk factors for recurrence (R0 but close margins, location/size, microscopic perineural invasion, recurrent primary disease, immunosuppression, thickness including Breslow and Clark level, poorly-moderately differentiated)
No indication of regional nodal RT
No prior RT to the treated site
Written consent from patient or his/her legal representative, trustworthy person or family member if the person is physically unable to give his or her written consent
Life expectancy ≥ 6 months, as clinically estimated by the investigator in charge of enrolment
No contraindication for surgery and RT after multidisciplinary board meeting evaluation
Affiliated to a social security scheme

Exclusion Criteria:

Macroscopic incomplete resection of the primary tumor (≥ R1)
Patient with severe dementia not allowing follow-up
Any psychological, familial, sociological, geographical or logistical reasons that would prevent participation to surveillance during treatment and follow-up
Other active cancers in treatment
Participation in another interventional study (therapeutic trial interfering with the study's endpoints)
Patient on AME (state medical aid)
Persons deprived of their liberty by a judicial or administrative decision

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT05794035

Other Study ID Numbers:

APHP180682

First Posted:

Mar 31, 2023

Last Update Posted:

Mar 31, 2023

Last Verified:

Jan 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Assistance Publique - Hôpitaux de Paris

Non Melanoma Skin Cancer

Adjuvant radiation therapy

older patient

Additional relevant MeSH terms:

Skin Neoplasms

Study Results

No Results Posted as of Mar 31, 2023