Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial

Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases

This trial compares cryoablation combined with stereotactic body radiation therapy to stereotactic body radiation therapy alone to see how well they work in treating patients with pain from cancer that has spread to the bones (bone metastases). Bone is a common site of metastasis in advanced cancer, and bone metastases often result in debilitating cancer-related pain. The current standard of care to treat painful bone metastases is radiation therapy alone. However, many patients do not get adequate pain relief from radiation therapy alone. Another type of therapy that may be used to provide pain relief from bone metastases is cryoablation. Cryoablation is a procedure in which special needles are inserted into the tumor site. These needles grow ice balls at their tips to freeze and kill cancer cells. The goal of this trial is to compare how well cryoablation in combination with radiation therapy works to radiation therapy alone when given to cancer patients to provide pain relief from bone metastases.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Renal Cell Carcinoma; Metastatic Melanoma; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Metastatic Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Bone; Metastatic Urothelial Carcinoma; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Metastatic Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Metastatic Sarcoma; Metastatic Thyroid Gland Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Procedure: Cryosurgery; Radiation: Stereotactic Body Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the efficacy of cryoablation in combination with stereotactic body radiation therapy (SBRT) or SBRT only for the treatment of painful bone metastases.

SECONDARY OBJECTIVES:

I. To assess for narcotics utilization by daily morphine equivalent dose. II. To assess duration of pain response reported by International Pain Response Criteria.

III. To assess for local tumor control. IV. To assess for changes in patient quality of life with Brief Pain Inventory (BPI) score.

V. To assess for adverse event rates. VI. To assess incidence and severity of adverse events/toxicity. VII. To assess technical success for cryoablation.

EXPLORATORY OBJECTIVE:

I. To investigate the local microenvironmental changes following SBRT and cryoablation combined with SBRT to bone metastases.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo stereotactic body radiation therapy for 1 fraction.

ARM B: Patients undergo cryoablation. Within 10 days after cryoablation, patients undergo stereotactic body radiation therapy for 1 fraction.

After completion of study treatment, patients are followed up at 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rahul A. Sheth, MD; Phone Number: 713-745-0652; Email: rasheth@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Rahul A. Sheth, MD; Phone Number: 713-745-0652
      • Principal Investigator: Rahul A. Sheth, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient must have a primary diagnosis of malignancy and radiographic evidence of bone metastases. Eligible tumor histologies include the following malignancies with low alpha/beta ratios: renal cell carcinoma, urothelial carcinomas, castration-resistant prostate cancer, sarcoma, thyroid carcinoma, colorectal carcinoma, and melanoma

• A target lesion the meets the following criteria:

  • The target lesion must be amenable to both cryoablation and SBRT, as determined by the study principal investigators (PIs)
  • The target lesion must be =< 7cm
  • The pain due to the target lesion must be at least 4/10 based on the BPI pain scale
  • Pain from the metastatic site must correlate with an identifiable tumor on computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US) imaging
• Life expectancy >= 3 months
• Platelet count > 50,000/mm^3 within 6 weeks of screening
• International normalized ratio (INR) < 1.5 within 6 weeks of screening
• If taking antiplatelet or anticoagulation medication, it must be able to be discontinued 48 hours prior to the procedure or at the discretion of the PI (e.g., aspirin, ibuprofen, low molecular weight heparin [LMWH] preparations)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) within 6 weeks of screening
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization. Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization
• All lines of prior systemic therapy are permissible. Standard concurrent chemotherapy, immunotherapy, or targeted therapy are permissible
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior locoregional therapy to target lesion, including ablation of any modality, embolization, radiation, or surgery
• Patient may not be receiving any other investigational agents. Standard concurrent chemotherapy, immunotherapy, or targeted therapy will be allowed
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or nursing women; women of childbearing potential unless using effective contraception as determined by the investigator
• Target lesions that involve the spinal column or calvarium
• Absolute neutrophil count < 1000 mm^3 within 6 weeks of screening
• Active infection
• Presence of confirmed pathologic fracture at the target lesion not amenable to percutaneous stabilization
• Lesions that involve a weight-bearing long bone of the lower extremity with the tumor causing > 50% loss of cortical bone. Lesions involving the hands and feet

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (SBRT); Patients undergo stereotactic body radiation therapy for 1 fraction.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Radiation: Stereotactic Body Radiation Therapy; Undergo stereotactic body radiation therapy; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy
Experimental: Arm B (cryoablation, SBRT); Patients undergo cryoablation. Within 10 days after cryoablation, patients undergo stereotactic body radiation therapy for 1 fraction. Alternatively, patients may receive stereotactic body radiation therapy initially, followed by cryoablation."	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Cryosurgery; Undergo cryoablation; Other Names: Cryoablation; cryosurgical ablation; Ablation, Cryo; Radiation: Stereotactic Body Radiation Therapy; Undergo stereotactic body radiation therapy; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response	Defined as complete or partial response as reported by the International Pain Response Criteria at the site of the treated bone metastasis based on the BPI pain score and daily morphine equivalent (MEDD). Will be summarized separately for each treatment arm with associated 95% exact confidence intervals.	At 12 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily morphine equivalent (MEDD)		Baseline, assessed up to 24 weeks post-treatment
Duration of response	Will be assessed by performing area under the curve (AUC) analysis of Brief Pain Inventory (BPI) pain scores.	Up to 24 weeks post-treatment
Local control	Will be determined by imaging evidence of residual viable tumor. Standard of care cross-sectional imaging and bone scintigraphy will be performed at 3 month intervals.	Up to 24 weeks post-treatment
Rate and severity of adverse and serious related adverse events	Point estimates and two-sided 95% confidence intervals will be generated for procedural related adverse events.	Within 30 days of the last study treatment
Technical success for cryoablation	Will be determined by identifying on intra-procedural imaging when the leading edge of the ice successfully extends beyond the tumor margin by at least 5 mm.	Up to 24 weeks post-treatment

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Rahul A Sheth, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: October 13, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Prostatic Diseases; Thyroid Diseases; Head and Neck Neoplasms; Kidney Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Neoplasms; Carcinoma, Renal Cell; Prostatic Neoplasms; Carcinoma; Colorectal Neoplasms; Thyroid Neoplasms
• Other Study ID Numbers: 2019-1234 (Other Identifier: M D Anderson Cancer Center); NCI-2020-07368 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No