Efficacy of Cryotherapy Combined or Not With Analgesics in Uncontrolled Painful Musculoskeletal Metastasis (CRYO)

Randomized Controlled Multicenter Prospective Open-label Study of the Efficacy of the Percutaneous Cryotherapy Combined or Not With a Medical Analgesia in the Treatment of Patients With Uncontrolled Painful Musculoskeletal Metastasis

The primary objective of this trial is to compare the efficacy of 2 analgesic strategies, based on percutaneous cryotherapy plus medical supportive care versus medical supportive care alone in the treatment of cancer patients with painful musculoskeletal metastasis.

Study Overview

• Status: Terminated
• Conditions: Musculoskeletal Pain
• Intervention / Treatment: Other: Cryotherapy + Medical analgesics; Drug: Medical Analgesics

Detailed Description

There is a substantial body of evidences that support the rationale for percutaneous cryotherapy in the treatment of painful musculoskeletal metastasis. Since the available results are based exclusively on retrospective and single-arm prospective studies, all authors agree that preliminary data deserves further investigation to provide high level evidences.

Current knowledge, along with the need for relieving patients' pain, already leads interventional radiologists to introduce analgesic cryotherapy in their routine practice. Our team usually notes a clinically significant pain relief that is immediate, continuous and prolonged in these patients. However, facing the lack of comparative studies, this technique is still proposed to patients with poor life-expectancy.

Percutaneous cryotherapy is an innovative strategy in the treatment of patients with uncontrolled painful metastases. It could provide a significant and durable pain relief and a better quality of life, earlier in the patient's care pathway.

The study group hypotheses that an early procedure of percutaneous cryotherapy is able to provide painful patients with better and prolonged analgesia and quality of life.

A prospective controlled study is proposed with two analgesic strategies (percutaneous cryotherapy plus medical supportive care versus medical supportive care alone) in patients with a painful metastasis not controlled by conventional analgesia strategy.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Montpellier, France, 34298
    • Institut de Cancérologie de Montpellier-Val d'Aurelle
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest - Centre René Gauducheau
  • Strasbourg, France, 67065
    • Institut Paul Strauss
  • Strasbourg, France, 67091
    • CHRU de Strasbourg
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years at the day of consenting to the study;
• Patient with at least 1 painful metastasis with a musculoskeletal involvement;
• Patient referred to a Pain Management Unit to optimize the analgesic strategy;

• Painful metastatic lesion that fulfils with all the following :

  • Pain must be correlated with an identifiable lesion on imaging (Computed Tomography, Magnetic Resonance Imaging or Ultrasonography)
  • Level of mean pain within the past 24 hours of at least 4/10 (numeric rating scale)
  • Painful metastasis suitable for a procedure of percutaneous cryotherapy
• Life-expectancy longer than 6 months;
• Performance Status of the ECOG ≤2;
• Neutrophils count > 1 Gi/l within the past 14 days;
• Adequate coagulation panel (as per the investigator judgement);
• Ability to understand and willingness for follow-up visits;
• Covered by a medical insurance;
• Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment.

Exclusion Criteria:

• Patient with a primary tumor of leukemia, lymphoma or myeloma;
• Tumor involving a weight bearing long bone of the lower limbs with the tumor causing more than 50% of cortical bone;
• Lesion amenable to any curative intervention;
• Formal indication for local analgesic procedure other than percutaneous cryotherapy;
• Prior radiotherapy on the targeted lesion within the 3 weeks prior to randomization;
• Patient with any contraindication for the procedure of percutaneous cryotherapy, including treatment requiring ice ball formation within 0.5 cm of the spinal cord, brain, other critical nerve, structure, large abdominal vessels such as the aorta or inferior vena cava, bowel or bladder (except if active or passive thermic protection can be performed);
• Uncontrolled coagulopathy or bleeding disorders;
• Evidence of pregnancy, breast-feeding, or patient wishing to become pregnant during the study;
• Active, uncontrolled infection;
• Any cognitive impairment or any disease that may restrain the use of numeric scales and the administration of quality of life questionnaires;
• Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would likely interfere with study procedures or results;
• Concurrent participation in other experimental studies that could interfere with the primary endpoint assessment.

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
Experimental: Cryotherapy + medical analgesics; Percutaneous Cryotherapy and medical analgesics according to the investigator's discretion	Other: Cryotherapy + Medical analgesics; Percutaneous cryotherapy: A complete cycle of treatment will require 2 freezing 10-minutes periods, separate by a 9-minutes passive and 1-minute active thaw, with the cryoablation system. Dimension of the iceball coverage above the tumor will be monitored by non-contrast CT or MRI during the freezing cycle. Medical supportive care: Best analgesic therapy at investigator's discretion; Other Names: Percutaneous cryotherapy + Medical analgesics
Active Comparator: Medical analgesics; Medical analgesics alone according to the investigator's discretion	Drug: Medical Analgesics; Best analgesic therapy at investigator's discretion; Other Names: Best medical medical analgesics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to analgesic strategy failure	Failure will be defined as at least, one of the following situations: Reescalation of the mean local pain by 2 points or more from the lowest pain score from baseline; Absence of pain relief ≥ 2 points 3 months after randomization; Indication of any other loco regional analgesic procedure (radiotherapy, interventional radiology or surgery).	Time from the date of randomization to the date of analgesic strategy failure assessed up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of pain relief	Percentage of pain relief from baseline, rated by patients	Weekly for the first 3 months, then monthly assessed up to 6 months
Depth of local pain relief	Evaluation using the numeric rating scale	Numeric rating scale (scale range from 0 [no pain] to 10 [worst imaginable pain]): Weekly for the first 3 months, then monthly assessed up to 6 months
Depth of local pain relief	Evaluation using the Brief Pain Inventory	Brief Pail Inventory : Monthly assessment up to 6 months
The impact of local pain on the patient's quality of life	Using the FACT-BP questionnaire	Monthly assessment up to 6 months
The impact of local pain on the patient's quality of life	Using the EuroQOL-5Dimensions-5Levels questionnaire	Monthly assessment up to 6 months
Description of analgesic consumption	Using a booklet completed by the patients and/or the investigator	Weekly for the first 3 months, then monthly assessed up to 6 months
Overall Survival	Time from the date of randomization to the date of death due to any cause	From date of randomization to date of death from any cause or date of LPLV (estimated date: March 2020)
Tolerance profile	Tolerance assessed according to the NCI-CTC AE version 4	Date of last visit (Month 6 +/- 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness analysis	All the resources consumption will be collected during the 6-months timeframe: Hospitalization costs (outpatient, inpatient, and home care), external consultations and wider examinations (eg MRI), transportation costs.	Date of last visit (Month 6 +/- 28 days)
Cost-utility analysis	All the resources consumption will be collected during the 6-months timeframe: Hospitalization costs (outpatient, inpatient, and home care), external consultations and wider examinations (eg MRI), transportation costs.	Date of last visit (Month 6 +/- 28 days)
Budget impact analyses	Quantication of financial consequences of rolling out the innovative strategy throughout the health system (i.e. the replacement of Medical supportive care by Medical supportive care + Percutaneous cryotherapy)	One-year baseline period. Will be performed in case the experimental strategy dominates the standard strategy

Collaborators and Investigators

• Sponsor: Centre Leon Berard
• Investigators: Principal Investigator: Charles MASTIER, MD, Centre Léon Bérard

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2018
• Primary Completion (Actual): May 30, 2020
• Study Completion (Actual): August 30, 2020

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (Actual): February 22, 2018

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Musculoskeletal metastasis; Cancer pain; Percutaneous cryotherapy; Medical supportive care
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neoplastic Processes; Neoplasm Metastasis; Musculoskeletal Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics
• Other Study ID Numbers: ET17-016 (Cryoanalgesia)

Drug and device information, study documents

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