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Low Dose Continuous Cyclophosphamide vs Standard Doxorubicin in Advanced Sarcoma Elderly Patients (METROPHOLYS)

Primary Purpose

Soft Tissue Sarcoma Adult

Status
Recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Cyclophosphamide
Doxorubicin
Sponsored by
Istituto Oncologico Veneto IRCCS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma Adult

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients may be included in the study only if they meet all the following criteria:

  1. Histologically proven diagnosis of soft tissue sarcoma.
  2. Advanced unresectable or metastatic soft tissue sarcoma not previously treated with chemotherapy for metastatic disease.
  3. At least one measurable lesion according to RECIST1.1 criteria.
  4. Availability of a tumor sample (primary and/or metastatic sites).
  5. Age ≥ 70 years (70-75 years if UNFIT at G8; >75 independent of G8 score)
  6. ECOG PS 0-2.
  7. Life expectancy of at least 12 weeks.
  8. Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl.
  9. Adequate hepatic function, defined as: Total bilirubin ≤ 1.5 time the upper-normal limits (ULN) of the normal values, ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x ULN (or <5 x ULN in case of liver metastases)
  10. Alkaline phosphatase ≤ 2.5 x ULN (or <5 x ULN in case of liver metastases).
  11. Creatinine clearance ≥ 30 mL/min.
  12. Normal cardiac function, with left ventricular ejection fraction (LVEF) ≥50%.
  13. Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator
  14. Geriatric assessment by means of G8 screening tool and CRASH score.
  15. Will and ability to comply with the protocol.
  16. Written informed consent to study participation.

Exclusion Criteria:

  • Patients will be excluded from the study for any of the following reasons:

    1. Previous treatment for metastatic disease.
    2. Previous (neo) adjuvant chemotherapy with anthracyclines.
    3. Radiotherapy to any site within 4 weeks before the study.
    4. Untreated brain metastases or spinal cord compression or primary brain tumors.
    5. Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
    6. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication.
    7. Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer)
    8. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
    9. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
    10. Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
    11. Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
    12. Sexually active males unwilling to practice contraception during the study and until 6 months after the last trial treatment.

Sites / Locations

  • Policlinico Sant'Orsola MalpighiRecruiting
  • Istituto Clinico HumanitasRecruiting
  • Istituto Ortopedico Rizzoli IRCCS
  • Fondazione del Piemonte per l'Oncologia IRCCS
  • IRST Romagnolo IRCCSRecruiting
  • Istituto Nazionale Tumori IRCCS
  • Istituto Oncologico Veneto IRCCSRecruiting
  • AOU Policlinico Giaccone Palermo
  • Ospedale Misericordia e Dolce
  • Policlinico Universitario Campus BiomedicoRecruiting
  • IFO - Istituto Regina Elena
  • Presidio Sanitario Humanitas - Gradenico
  • AOUI Policlinico Borgo RomaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Metronomic cyclophosphamide

Doxorubicin

Arm Description

Cyclophosphamide 50 mg daily per os continuously; Patients will be visited for re-cycling every three weeks. Metronomic cyclophosphamide will be taken in the morning along with a full glass of water.

Doxorubicin 60 mg/mq i.v. in 10 minutes, day 1; to be repeated every three weeks up to a maximum of 6 cycles.

Outcomes

Primary Outcome Measures

Time to treatment failure
Progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment. Toxicity is assessed according to NCI-CTCAE criteria v. 4.03

Secondary Outcome Measures

Progression free Survival
Progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment.
Overall survival
Overall Survival is defined as the time from date of randomization to the date of death due to any cause
Overall Toxicity Rate
Toxicities will be recorded, classified, graded and managed according to NCI CTCAE v. 4.03.

Full Information

First Posted
November 25, 2020
Last Updated
March 31, 2022
Sponsor
Istituto Oncologico Veneto IRCCS
Collaborators
Ministry of Health, Italy
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1. Study Identification

Unique Protocol Identification Number
NCT04656262
Brief Title
Low Dose Continuous Cyclophosphamide vs Standard Doxorubicin in Advanced Sarcoma Elderly Patients
Acronym
METROPHOLYS
Official Title
The METROPHOLYS Study Metronomic Cyclophosphamide vs Doxorubicin in Elderly Patients With Advanced Soft Tissue Sarcomas Randomized, Controlled Open Label Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 10, 2018 (Actual)
Primary Completion Date
July 31, 2022 (Anticipated)
Study Completion Date
January 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Oncologico Veneto IRCCS
Collaborators
Ministry of Health, Italy

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To compare the efficacy, as measured by time to treatment failure, of metronomic cyclophosphamide with respect to doxorubicin in elderly patients affected by mSTS.
Detailed Description
This phase III randomized clinical trial was designed to compare metronomic Cyclophosphamide with standard Doxorubicin for the first-line treatment of elderly cancer patients with advanced inoperable or metastatic STS: i) ARM A (experimental): Metronomic Cyclophosphamide ii) ARM B (control): Doxorubicin up to six cycles

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metronomic cyclophosphamide
Arm Type
Experimental
Arm Description
Cyclophosphamide 50 mg daily per os continuously; Patients will be visited for re-cycling every three weeks. Metronomic cyclophosphamide will be taken in the morning along with a full glass of water.
Arm Title
Doxorubicin
Arm Type
Active Comparator
Arm Description
Doxorubicin 60 mg/mq i.v. in 10 minutes, day 1; to be repeated every three weeks up to a maximum of 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Endoxan
Intervention Description
Cyclophosphamide is formulated as coated tablets of 50mg for oral administration
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Doxorubicin is formulated as 60 mg/mq for infusional use (i.v use)
Primary Outcome Measure Information:
Title
Time to treatment failure
Description
Progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment. Toxicity is assessed according to NCI-CTCAE criteria v. 4.03
Time Frame
From date of randomization until the date of treatment discontinuation due to disease progression, toxicity leading to treatment discontinuation, or death, whichever occurs first, assessed up to 12 months
Secondary Outcome Measure Information:
Title
Progression free Survival
Description
Progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment.
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Title
Overall survival
Description
Overall Survival is defined as the time from date of randomization to the date of death due to any cause
Time Frame
Time from randomization to the date of death due to any cause or last follow up assessed up to 12 months
Title
Overall Toxicity Rate
Description
Toxicities will be recorded, classified, graded and managed according to NCI CTCAE v. 4.03.
Time Frame
From signing IC until 30 days after last study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients may be included in the study only if they meet all the following criteria: Histologically proven diagnosis of soft tissue sarcoma. Advanced unresectable or metastatic soft tissue sarcoma not previously treated with chemotherapy for metastatic disease. At least one measurable lesion according to RECIST1.1 criteria. Availability of a tumor sample (primary and/or metastatic sites). Age ≥ 70 years (70-75 years if UNFIT at G8; >75 independent of G8 score) ECOG PS 0-2. Life expectancy of at least 12 weeks. Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl. Adequate hepatic function, defined as: Total bilirubin ≤ 1.5 time the upper-normal limits (ULN) of the normal values, ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x ULN (or <5 x ULN in case of liver metastases) Alkaline phosphatase ≤ 2.5 x ULN (or <5 x ULN in case of liver metastases). Creatinine clearance ≥ 30 mL/min. Normal cardiac function, with left ventricular ejection fraction (LVEF) ≥50%. Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator Geriatric assessment by means of G8 screening tool and CRASH score. Will and ability to comply with the protocol. Written informed consent to study participation. Exclusion Criteria: Patients will be excluded from the study for any of the following reasons: Previous treatment for metastatic disease. Previous (neo) adjuvant chemotherapy with anthracyclines. Radiotherapy to any site within 4 weeks before the study. Untreated brain metastases or spinal cord compression or primary brain tumors. Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication. Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer) Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication. Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs. Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies. Sexually active males unwilling to practice contraception during the study and until 6 months after the last trial treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gian Luca De Salvo
Phone
0039-049-8215710
Email
gianluca.desalvo@iov.veneto.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonella Brunello
Organizational Affiliation
Istituto Oncologico Veneto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Policlinico Sant'Orsola Malpighi
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margherita Nannini, MD
Facility Name
Istituto Clinico Humanitas
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Marrari, MD
Facility Name
Istituto Ortopedico Rizzoli IRCCS
City
Bologna
ZIP/Postal Code
40136
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emanuela Palmerini, MD
Facility Name
Fondazione del Piemonte per l'Oncologia IRCCS
City
Candiolo
ZIP/Postal Code
10060
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Grignani, MD
Facility Name
IRST Romagnolo IRCCS
City
Meldola
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Toni Ibrahim, MD
Facility Name
Istituto Nazionale Tumori IRCCS
City
Milano
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvia Stracchiotti, MD
Facility Name
Istituto Oncologico Veneto IRCCS
City
Padova
ZIP/Postal Code
35128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonella Brunello, PhD
Facility Name
AOU Policlinico Giaccone Palermo
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe Badalamenti, MD
Facility Name
Ospedale Misericordia e Dolce
City
Prato
ZIP/Postal Code
59100
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giacomo GI Baldi, MD
Facility Name
Policlinico Universitario Campus Biomedico
City
Roma
ZIP/Postal Code
00128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno Vincenzi, MD
Facility Name
IFO - Istituto Regina Elena
City
Roma
ZIP/Postal Code
00144
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Virginia Ferraresi, MD
Facility Name
Presidio Sanitario Humanitas - Gradenico
City
Torino
ZIP/Postal Code
10153
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alessandro Comandone, MD
Facility Name
AOUI Policlinico Borgo Roma
City
Verona
ZIP/Postal Code
37134
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sara Cingarlini, MD

12. IPD Sharing Statement

Learn more about this trial

Low Dose Continuous Cyclophosphamide vs Standard Doxorubicin in Advanced Sarcoma Elderly Patients

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