Palliative Radiotherapy in Symptomatic Pelvic Soft Tissue Tumors

Gynecologic Cancer Clinical Trial

— PALLSOFT  

Official title:

Palliative Radiotherapy in Symptomatic Pelvic Soft Tissue Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06398314
• Other study ID #: 606316 (REK)
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2024
• Est. completion date: December 2030

Study information

• Verified date: May 2024
• Source: Sykehuset Telemark
• Contact: Kjersti Skipar, MD
• Phone: +47 98444114
• Email: kjeski[@]sthf.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PALLSOFT is a randomized, open-label, non-inferiority phase III, multicenter, national trial that will investigate whether the patient-reported symptomatic effect of palliative radiotherapy delivered in 1-2 fractions is non-inferior to palliative radiotherapy delivered in five fractions in patients with pelvic soft tissue tumors from either gastrointestinal, urological or gynecological cancer. Health-related quality of life, toxicities, survival and prognostic and predictive biomarkers will be assessed as secondary and explorative endpoints.

Description:

Studies and clinical practice have proven palliative radiotherapy to provide efficient symptom relief in patients with symptomatic pelvic soft tissue tumors. However, studies are mainly retrospective, are difficult to compare due to a variety of radiotherapy fractionation schedules used, and lack data on patient-reported quality of life. Consequently, no recommended standard of care is established, and several schedules are employed with variations in both number of fractions and total radiation dose (measured in Gray=Gy). Given the limited life expectancy of palliative patients, a short-course radiotherapy schedule would be preferable provided efficient symptom relief and good health-related quality of life.

PALLSOFT is a national, randomized, non-inferiority study that will investigate whether the symptomatic effect of a short-course radiotherapy schedule of 8 Gy x 1-2 is non-inferior to a more prolonged schedule of 5 Gy x 5. The study will include patients with symptomatic pelvic soft tissue tumors from either gastrointestinal, urological or gynecological cancer. Patients will defined a target symptom from 5 predefined cathegories (pain, bleeding, bowel/lower urinary tract/vaginal dysfunction), and change in symptom intensity will be assessed, as well as overall toxicities, quality of life and survival. Prognostic and predictive biomarkers will be explores, the latter with particular emphasis on the significance of tumor hypoxia in palliative radiotherapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: December 2030
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients unsuitable for curative treatment due to either advanced disease or medical contradictions (i.e comorbidity, old age, poor general condition)

• Histologically verified primary cancer originated from gastrointestinal, urological or gynecological organs (histological verification can be performed on other lesions than the symptomatic pelvic tumor)

• Primary, residual, recurrent or metastatic pelvic tumor from the above-mentioned cancers not amenable for curative treatment

• Tumor-related symptoms including within the 5 defined categories pain, bleeding, bowel/lower urinary/vaginal dysfunction

• Considered candidate for palliative radiotherapy according to both study arms

• Patient reported severity of symptoms =4 on a NRS- scale of 0-10

• =18 years of age

• Speaks and understands Norwegian or English

• Ability to understand and willing to sign a written informed consent

• ECOG performance status 0-3

• Able to pause systemic cancer treatment for one week prior to, during, and one week after the radiotherapy treatment

• Women of childbearing potential (WOCBP) should have a negative highly sensitive serum pregnancy test within 72 hours prior to study intervention. WOCBP must agree to the use of highly effective birth control methods or abstain from heterosexual sexual activity from randomization and until completed study intervention

Exclusion Criteria:

• Neuroendocrine histology of any kind

• Sarcoma or sarcomal components in the histology

• Tumors that originate from bony metastases without a soft tissue component

• Unable to comply with study questionnaires

• Ongoing treatment with an investigational drug at inclusion

• Planned inclusion in another interventional clinical trial within 4 weeks after radiotherapy

• Patients who are pregnant due to risk of teratogenic and abortifacient effects of radiotherapy

Related Conditions & MeSH terms

• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• Gynecologic Cancer
• Soft Tissue Neoplasms
• Urologic Cancer
• Urologic Neoplasms

Intervention

Radiation:
• Palliative radiotherapy
Hypofractionated radiotherapy

Locations

Country	Name	City	State
n/a

Sponsors (12)

Lead Sponsor	Collaborator
Sykehuset Telemark	Haukeland University Hospital, Helse Stavanger HF, Hospital of Southern Norway Trust, Møre og Romsdal Hospital Trust, Nordlandssykehuset HF, Oslo University Hospital, South-Eastern Norway Regional Health Authority, St. Olavs Hospital, Sykehuset Innlandet HF, University Hospital of North Norway, Vestre Viken Hospital Trust

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient-reported quality of life	Establish whether 1-2 fractions of 8 Gy is non-inferior to 5 fractions of 5 Gy with regards to quality of life assessed by EORTC-QLQ C15PAL (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core15 Palliative)	12 weeks
Other	Prognostic models	Explore prognostic models for patient classification: Glasgow Prognostic Score (GPS): C-Reactive Protein (CRP, mg/L), Albumin (g/L) GPS 0 = Normal level CRP and albumin GPS 1: Increased CRP or low albumin GPS 2: Increased CRP and low albumin	Baseline
Other	Prognostic models	Explore prognostic models for patient classification: LabBM: CRP (mg/L), LDH (lactate dehydrogenase, U/L), Albumin (g/L), hemoglobin (g/dL), platelets (E09/L) The score is calculated as follows; CRP and LDH above upper limit of normal=1 point for each parameter. Albumin, hemoglobin and platelets below the lower limit of normal: 0.5 point for each parameter. Minimum score 0 point, maximum score 3.5 points. Low score indicates a more favorable prognosis	Baseline
Other	Prognostic models	Explore prognostic models for patient classification: LabPS: CRP (mg/L), LDH (lactate dehydrogenase, U/L), Albumin (g/L), hemoglobin (g/dL), platelets (E09/L), Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) The score is calculated as follows; CRP and LDH above upper limit of normal=1 point for each parameter. Albumin, hemoglobin and platelets below the lower limit of normal: 0.5 point for each parameter. ECOG PS 3-4, 2 and 0-1: 1, 0.5 and 0 points,respectively Minimum score 0 point, maximum score 4.5 points. Low score indicates a more favorable prognosis	Baseline
Other	Predictive biomarkers MRI	Magnetic Resonance Images (MRI) previously acquired for diagnosis, treatment and/or follow up will be collected. Hypoxia images will be generated using the Consumption and Supply- based Hypoxia (CSH) Imaging Method. The tumor hypoxic fraction (HF) will be calculated on hypoxia images and explored as a potential explanatory response variable in individual patients.	Baseline
Other	Predictive biomarkers tumor biopsies	Tumor biopsies previously acquired for diagnosis, treatment and/or follow up will be collected. Tumor RNA will be isolated from paraffin embedded tissue blocks, subjected to global gene expression analysis and used to indicate hypoxia by applying previously established gene signatures. Gene signatures will be explored as potential explanatory response variable in individual patients.	Baseline
Primary	Patient-reported symptomatic effect	Establish whether 1-2 fractions of 8 Gy is non-inferior to 5 fractions of 5 Gy with regards to target symptom effect assessed by change in NRS 0-10 (Numerical Rating Scale) from baseline	12 weeks
Secondary	Physician-reported toxicities	Establish whether 1-2 fractions of 8 Gy is non-inferior to 5 fractions of 5 Gy with regards to bladder and bowel toxicities assessed by CTCAE	52 weeks
Secondary	Survival	Establish whether 1-2 fractions of 8 Gy is non-inferior to 5 fractions of 5 Gy with regards to overall survival	2 years