Proton Versus Photon Therapy in Anal Squamous Cell Carcinoma (SWANCA)

Proton Versus Photon Therapy in Anal Squamous Cell Carcinoma - Swedish Anal Carcinoma Study

Dosimetric studies suggest that radiotherapy with protons has a potential to reduce side effects compared to treatment with photons for patients with anal carcinoma (AC). There are so far no studies comparing these treatment techniques in a randomised setting. The aim of this study is to compare side effects following photon therapy versus proton therapy within the framework of a randomised controlled trial.

Study Overview

• Status: Recruiting
• Conditions: Anal Cancer Squamous Cell
• Intervention / Treatment: Radiation: Photon radiotherapy; Radiation: Proton radiotherapy

Detailed Description

Anal carcinoma is a disease in which modern therapy is reasonably successful in achieving tumour control/cure. Both acute and late side effects are substantial. Proton radiotherapy is hypothesised to have the potential to decrease the incidence/severity of some acute side effects from certain organs at risk e.g. bone marrow and intraperitoneal bowel. By sparing the dose to these organs it is also possible that late effects might be less evident. Sparing of the bone marrow may lead to fewer septic events and dose reductions of chemotherapy which may, as a consequence, improve tumour control. The primary aim of this study is to find ways to decrease acute side effects primarily to alleviate some discomfort from the patient during and after a usually painful treatment experience. It has also been concluded by others that reduction of acute side effects is a relevant aim and end point for the evaluation of new treatment techniques and both patient reported and physician reported data are assessed

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Björn U Zackrisson, MD; Phone Number: 51564 +46907850000; Email: bjorn.zackrisson@umu.se
• Study Contact Backup: Name: Martin P Nilsson, MD; Phone Number: +4640333011; Email: martin.p.nilsson@skane.se

Study Locations

• Sweden
  • Umeå, Sweden, 901 85
    • Recruiting
    • Umeå University Hospital
    • Contact: Birgitta Lindh, MD; Phone Number: 52442 +46907850000; Email: birgitta.lindh@regionvasterbotten.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient must be at least 18 years old
2. Histologically confirmed, previously untreated squamous cell carcinoma (p16-positive or p16-negative) of the anal canal (ICD-O-3 C21), i.e. cancer of the perianal skin without connection to the anal canal are not included. The patients may have primary tumour, regional nodes, metastasis (TNM)-stage T2 (>4 cm) -4,N0-1c,M0 (UICC 8th edition).
3. World Health Organisation/Eastern Cooperative Oncology Group (WHO/ECOG) performance status 0-1
4. The patient must be able to understand the information about the treatment and give a written informed consent.

Exclusion Criteria:

1. Patients with cancer of the perianal skin without involvement of the anal canal (ICD-O-3 C44.5) are not eligible.
2. Patient judged to have any other treatment than radiotherapy with concomitant chemotherapy as the preferred treatment
3. Concomitant or previous malignancies. Exceptions are, adequately treated basal cell carcinoma or squamous cell carcinoma of the skin or, other previous malignancy with a disease-free interval of at least 5 years.
4. Two or more synchronous primary cancers in the pelvic region at time of diagnosis
5. Previous radiotherapy, surgery or chemotherapy that may interfere with the planned treatment for the present disease, as judged by the investigator.
6. Co-existing disease prejudicing survival (expected survival should be >2 years).
7. Pregnancy or breast feeding
8. When prosthetic materials (e.g. hip prostheses) are present close to the target volume it must be considered if this may introduce uncertainties in dose calculations that precludes especially, proton therapy.
9. Patients with pacemaker/ICD are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Photon radiotherapy; Conventional photon radiation is delivered by volumetric arc therapy/intensity modulated radiotherapy/helical tomotherapy using simultaneous integrated boost (SIB) technique. The total dose to the primary tumour target and node metastases >2 cm is 57.5 Gy in 27 fractions, one fraction/day, five fractions/week during 5.5 weeks. Node metastases up to 2 cm will receive 50.5 Gy in 27 fractions. Elective lymph nodes will receive a total dose of 41.6 Gy.	Radiation: Photon radiotherapy; Conventional photon radiotherapy; Other Names: Volumetric arc therapy (VMAT), Intensity modulated radiotherapy (IMRT), helical tomotherapy
Experimental: Proton radiotherapy; Proton radiation is delivered by spot scanning. Proton plans will be produced by single field optimisation/single field uniform dose or multifield optimisation/intensity modulated proton therapy using simultaneous integrated boost (SIB) technique. The total dose to the primary tumour target and node metastases >2 cm is 57.5 Gy(RBE) in 27 fractions, one fraction/day, five fractions/week during 5.5 weeks. Node metastases up to 2 cm will receive 50.5 Gy(RBE) in 27 fractions. Elective lymph nodes will receive a total dose of 41.6 Gy(RBE).	Radiation: Proton radiotherapy; Proton radiotherapy; Other Names: Intensity modulated proton therapy (IMPT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute grade >2 hematological side effects	Acute hematological side effects will be assessed by weekly full blood cell counts during radiotherapy and the first three weeks after treatment completion. Side Grade >2 acute GI and haematological side-effects during therapy and up to three weeks after the end of treatment. Thereafter, every six weeks for up to three months after treatment. Results will be graded according to the Common Terminology Criteria for Adverse Events (NTCAE) v5.0 scoring system. Haematological adverse events will also be assessed by registering febrile episodes during an after treatment as well as the frequency of chemotherapy dose reduction or delayed chemotherapy.	Treatment start until three months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute grade >2 gastrointestinal side effects	Acute side-effects from the gastrointestinal tract are assess the NTCAE v5.0 scoring system by using. Patient reported side effects are assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific quality of life questionnaire for anal cancer, (QLQ-ANL27). During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).	Treatment start until three months after treatment
Acute side effects from skin	Acute side-effects from skin are assessed by using the Common Terminology Criteria for Adverse Events (NTCAE) v5.0 scoring system. Patient reported side effects are assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific questionnaire, QLQ-ANL27. During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).	Treatment start until three months after treatment
Acute side effects from the genitourinary tract	Acute side-effects from the genitourinary tract are assessed by scoring of genitourinary symptoms, pain by using the Common Terminology Criteria for Adverse Events (NTCAE) v5.0 scoring system. Patient reported side effects are assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific questionnaire, QLQ-ANL27. During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).	Treatment start until three months after treatment
Pain due to acute radiation reaction	Pain is assessed by using the NTCAE v5.0 scoring system. Patient reported pain is assessed by the European Organization for Research and Treatment of Cancer (EORTC), disease specific questionnaire, QLQ-ANL27. During radiotherapy, daily reported symptoms will be investigated by a newly developed symptom scale, Radiotherapy related symptom assessment scale (RSAS). The questionnaire includes 13 items specific for current diagnose. The RSAS is a validated instrument for assessing symptom intensity and distress in patients with different cancer disease undergoing radiotherapy, with psychometric properties within the expected range. Answering categories ranges from not at all to a great deal (1-4).	Treatment start until three months after treatment
Late side effects from the gastro-intestinal system	Late side effects 1, 2 and 5 years after completion of treatment. Side effects from the gastrointestinal system, are assessed by using the NTCAE v5.0 scoring system. Patient reported side effects are assessed by the EORTCs disease specific questionnaire, QLQ-ANL27.	From three months after treatment up to five years after treatment
Late side effects	Late side effects 1, 2 and 5 years after completion of treatment. Side effects from the genitourinary system are assessed by using the NTCAE v5.0 scoring system. Patient reported side effects are assessed by the EORTCs disease specific questionnaire, QLQ-ANL27.	From three months after treatment up to five years after treatment
Late side effects from skin	Late side effects 1, 2 and 5 years after completion of treatment. Side effects from the skin are assessed by using the NTCAE v5.0 scoring system. Patient reported side effects are assessed by the EORTCs disease specific questionnaire, QLQ-ANL27.	From three months after treatment up to five years after treatment
Assessment of Quality of life (QoL)	Patient reported quality of life during and after treatment assessed by • HRQoL will be investigated with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, the QLQ-C30, supplemented by the disease specific module (anal-cancer) QLQ-ANL27. • EuroQol (EQ-5D) is a generic QoL instrument designed for self-administration. The result could be expressed as a weight with values between zero and one (0-1). Together with information about survival the QoL weight can be expressed as quality-adjusted life-years (QALYs).	From randomisation up to 5 years
Primary tumour response	Frequency of complete tumour regression after primary treatment	3-6 months after treatment
Locoregional failure	Time from randomisation until first recurrence, local and/or regional	Up to five years after randomisation
Disease free survival	Time from randomisation until first recurrence, local/regional/systemic or death	Up to five years after randomisation
Overall survival	Time from randomisation until death	Up to five years after randomisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-utility analysis	Costs and QoL as well as clinical outcome measured as survival time will be considered. The results of the health-economic part of the study will be expressed as cost per quality adjusted life years (QALYs) saved of one intervention in comparison with the other. All relevant costs should be identified, quantified, and valued. Also indirect costs related to loss of production when patients cannot work due to the disease. All types of resources associated with the two treatment arms during the follow-up should be considered. E.g. costs for treatment of side-effects, costs for surgery when performed, and travelling costs for patients. Costing will be performed at the end of the study. For evaluation and analysis of the study results, a relatively simple health-economic model will be developed. This model will be used for evaluation of the two treatment arms from inclusion into the study until 5 years of follow up or death.	From randomisation until 5 years or death

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Region Västerbotten
• Investigators: Principal Investigator: Björn U Zackrisson, Prof, Umea university, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): March 28, 2030

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (Actual): July 8, 2020

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: side effects; proton beam therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Neoplasms, Squamous Cell; Rectal Neoplasms; Anus Diseases; Carcinoma, Squamous Cell; Anus Neoplasms
• Other Study ID Numbers: SWANCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data may be made available upon request from other researchers to the study group

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No