Focused Radiation Versus Systemic Therapy for Kidney Cancer Patients With Limited Metastasis, SOAR Study

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

Phase III Randomized Trial of Stereotactic Ablative Radiotherapy (SAbR) for Oligometastatic Advanced Renal Carcinoma (SOAR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05863351
• Other study ID #: EA8211
• Secondary ID: NCI-2023-02060EA
• Status: Recruiting
• Phase: Phase 3
• Start date: September 7, 2023
• Est. completion date: August 1, 2037

Study information

• Verified date: April 2024
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares the effect of stero-ablative radiotherapy (SAbR) followed by standard of care systemic therapy, to standard of care systemic therapy alone, in patients with kidney cancer that has spread from where it first started (primary site) to a limited (2-5) number of places in the body (metastatic). Study doctors want to find out if this approach is better or worse than the usual approach for metastatic kidney cancer. The usual approach is defined as the care most people get for metastatic kidney cancer which includes systemic therapy such as immunotherapy (given through the veins) and/or small molecular inhibitor (tablets taken by mouth). Radiotherapy uses high energy x-rays to kill cancer cells and shrink tumors. SAbR uses special equipment to position a patient and deliver radiation to tumors with high precision. Giving SAbR prior to systemic therapy may kill more tumor cells than the usual approach, which is systemic therapy alone.

Description:

PRIMARY OBJECTIVES:

I. To compare overall survival (OS) between patients receiving SAbR + systemic therapy (SABR+ST) versus systemic therapy (ST) only.

II. To compare average adverse event (AE) score between SAbR+ST arm and ST only arm.

SECONDARY OBJECTIVES:

I. To compare global health status / quality of life (QOL) between patients receiving SAbR+ST versus ST only.

II. To compare progression-free survival (PFS) between the arms.

EXPLORATORY OBJECTIVES:

I. To estimate PFS on first line systemic therapy (PFS-SST) in the SAbR+ST arm and compare with first line systemic therapy PFS of the ST arm.

II. To explore local control from SAbR by looking at the amount of local failures after SAbR in the SAbR+ST arm.

III. To assess the cost-effectiveness between the arms in terms of cost per unit gain in quality-of-life years.

QOL OBJECTIVES:

I. To compare global health status / quality of life (QOL) between patients receiving SabR+ST versus ST only using the National Comprehensive Cancer Network (NCCN) / Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index -19 item (NFKSI-19).

II. To compare quality-adjusted survival between patients randomized to receive SabR+ST vs ST alone using European Quality of Life (EUROQOL) 5-dimension, 5-level (EQ-5D-5L) at 3, 6, 9, 12, 18, and 24 months.

III. To compare global health status / QOL of the NFKSI-19 at all of the 3, 6, 9, 12, 18, and 24 month time points between patients randomized to receive SabR+ST versus ST alone.

IV. To compare scale scores of the NFKSI-19 (disease-related symptoms - physical disease-related symptoms - emotional, treatment side effects, and function & well-being) at 3, 6, 9, 12, 18, 24 months between patients randomized to receive SabR+ST versus ST alone.

V. To compare time to global quality of life deterioration between patients randomized to receive SabR+ST versus ST alone using NFKSI-19.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care systemic therapy on study.

ARM II: Patients undergo repeated SAbR until progression and then receive standard of care systemic therapy on study.

Patients in both arms undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 472
• Est. completion date: August 1, 2037
• Est. primary completion date: December 1, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must be >= 18 years of age

• Patient must have a pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma (RCC) prior to randomization

• Patient may have any RCC histology except a histology that has a sarcomatoid component

• Patient must have primary site addressed by local therapy. If the primary RCC is intact, the patient must undergo local treatment to the primary before randomization

• Patient must have favorable or intermediate International Metastatic RCC Database Consortium (IMDC) risk (0-2) at the time of randomization

• Patient must have a total of between 2 and 5 metastatic lesions, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with imaging obtained within 45 days prior to randomization

• Patient must have a documentation from a radiation oncologist confirming that all sites are amenable to SAbR

• Patient may have received prior therapy in the adjuvant setting as long as potential trial participants have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

• All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy

• A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:

• Has achieved menarche at some point

• Has not undergone a hysterectomy or bilateral oophorectomy

• Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

• Patient must have a Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

• Patients must have adequate organ and bone marrow function as per the recommended guidelines and the respective Food and Drug Administration [FDA] package insert required for the systemic therapy chosen by the treating oncologist. We recognize that patients may have varying levels of renal and liver function that will impact which systemic therapy is appropriate for the patient. We do not require all patients to have specific baseline laboratory thresholds but do ask the treating oncologist to attest that the patient has adequate organ and bone marrow function to safely receive one of the first line systemic therapies listed in the protocol as a standard of care treatment option

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study

• For patients with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If no previous history, testing for HBV is not required for entry onto the study

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. If no previous history, testing for HCV is not required for entry onto the study

• In order to participate in the QOL portion of the protocol, the patient must speak one of the languages in which the NFKSI-19 and EQ-5D-5L is available

• NOTE: Sites cannot translate the associated QOL forms

Exclusion Criteria:

• Patient must not have brain metastases

• Patient must not have metastasis involving the following locations: ultra-central (within 2cm of carina) lung, invading gastrointestinal tract (such as esophagus, stomach, intestines, colon, rectum), skin, and scalp

• Patient must not have received any prior systemic therapy (except for adjuvant setting) for metastatic RCC

• Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies

• Active tuberculosis (purified protein derivative [PPD] response without active TB is allowed)

• Uncontrolled hypertension (systolic blood pressure [BP] > 190mmHg or diastolic BP > 110mmHg)

• Major surgery within 30 days prior to randomization

• Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 30 days prior to randomization

• Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], cerebrovascular accident [CVA], etc.) events within 180 days prior to randomization

• Moderate or severe hepatic impairment (child-Pugh B or C)

• Untreated pulmonary embolism (PE) or deep-vein thrombosis (DVT) is not allowed. Treated PE or DVT is allowed > 30 days from diagnosis and when not resulting in respiratory impairment

• Unstable cardiac arrhythmia within 180 days prior to randomization

• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to randomization

• History of or active inflammatory bowel disease

• Malabsorption syndrome within 30 days prior to randomization

• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

• Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma
• Stage IV Renal Cell Cancer AJCC v8

Intervention

Procedure:
• Computed Tomography
Undergo CT
• Magnetic Resonance Imaging
Undergo MRI

Other:
• Questionnaire Administration
Ancillary studies

Procedure:
• Stereotactic Ablative Radiotherapy
Undergo SAbR
• Systemic Therapy
Given standard of care systemic therapy

Locations

Country	Name	City	State
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	UT Southwestern Simmons Cancer Center - RedBird	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	ECOG-ACRIN Cancer Research Group	Philadelphia	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Carle Cancer Center	Urbana	Illinois
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PFS-start of systemic therapy (SST)	Compare the PFS from the start of systemic therapy (instead of from the time of randomization) of Arm A (after PFS-SAbR) with PFS of upfront systemic therapy in Arm B. This endpoint will be descriptive and will only be explored in arm A. Will explore local control that SAbR provides, by looking at local failures after SAbR in SAbR+ST arm only. Local failure is defined as > 30% increase in the longest diameter of SAbR-treated lesion, more than 6 months post SAbR treatment.	From the start of SST to progression or death, assessed up to 10 years
Primary	Overall survival (OS)	The repeated confidence interval method will be utilized. At each scheduled interim analysis, a one-sided 95% repeated confidence interval of hazard ratio (stereotactic ablative radiotherapy [SAbR] + standard therapy [ST] / ST) will be computed, using the partial likelihood estimate, to test non-inferiority in OS for SAbR+ST arm.	From randomization to death from any cause, assessed up to 10 years
Primary	Incidence of adverse events (AEs)	All patients who receive treatment, regardless of eligibility, will be evaluated for AE/toxicity. AE score will be calculated in 3-month intervals starting from randomization. To calculate the AE score for a 3-month interval, for each patient, the AE sub-score for each Common Terminology Criteria for Adverse Events (CTCAE) categories (there are 26 AE categories listed in CTCAE version 5) will be aggregated based on the highest grade of AE experienced in each CTCAE category.	From randomization up to 6 months
Secondary	Progression-free survival (PFS)	Patients randomized to SAbR will need to first progress on SAbR, then progress on systemic therapy to be counted as an event for progression. Progression on SAbR is when SAbR (sequential SAbR) is unable to control the disease by meeting one of the two criteria: > 6 metastases in total requiring SAbR (no matter how many metastases a patient was randomized with), or one or more progressing lesions not amenable to SAbR (> 5% risk of grade 3 toxicity by American Society for Therapeutic Radiology and Oncology definition). This endpoint will be compared between the two arms using stratified log-rank test, at one-sided 0.025 significance level.	From randomization to progression of disease, assessed up to 10 years