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

Sponsor
Istituto Oncologico Veneto IRCCS (Other)
Overall Status
Recruiting
CT.gov ID
NCT04656262
Collaborator
Ministry of Health, Italy (Other)
132
13
2
52.7
10.2
0.2

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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:

  1. ARM A (experimental): Metronomic Cyclophosphamide ii) ARM B (control): Doxorubicin up to six cycles

Study Design

Study Type:
Interventional
Anticipated Enrollment :
132 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The METROPHOLYS Study Metronomic Cyclophosphamide vs Doxorubicin in Elderly Patients With Advanced Soft Tissue Sarcomas Randomized, Controlled Open Label Clinical Trial
Actual Study Start Date :
Sep 10, 2018
Anticipated Primary Completion Date :
Jul 31, 2022
Anticipated Study Completion Date :
Jan 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Metronomic cyclophosphamide

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.

Drug: Cyclophosphamide
Cyclophosphamide is formulated as coated tablets of 50mg for oral administration
Other Names:
  • Endoxan
  • Active Comparator: Doxorubicin

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

    Drug: Doxorubicin
    Doxorubicin is formulated as 60 mg/mq for infusional use (i.v use)

    Outcome Measures

    Primary Outcome Measures

    1. Time to treatment failure [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]

      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

    1. Progression free Survival [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]

      Progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment.

    2. Overall survival [Time from randomization to the date of death due to any cause or last follow up assessed up to 12 months]

      Overall Survival is defined as the time from date of randomization to the date of death due to any cause

    3. Overall Toxicity Rate [From signing IC until 30 days after last study treatment]

      Toxicities will be recorded, classified, graded and managed according to NCI CTCAE v. 4.03.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    70 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Policlinico Sant'Orsola Malpighi Bologna BO Italy 40138
    2 Istituto Clinico Humanitas Rozzano MI Italy 20089
    3 Istituto Ortopedico Rizzoli IRCCS Bologna Italy 40136
    4 Fondazione del Piemonte per l'Oncologia IRCCS Candiolo Italy 10060
    5 IRST Romagnolo IRCCS Meldola Italy 47014
    6 Istituto Nazionale Tumori IRCCS Milano Italy 20133
    7 Istituto Oncologico Veneto IRCCS Padova Italy 35128
    8 AOU Policlinico Giaccone Palermo Palermo Italy 90127
    9 Ospedale Misericordia e Dolce Prato Italy 59100
    10 Policlinico Universitario Campus Biomedico Roma Italy 00128
    11 IFO - Istituto Regina Elena Roma Italy 00144
    12 Presidio Sanitario Humanitas - Gradenico Torino Italy 10153
    13 AOUI Policlinico Borgo Roma Verona Italy 37134

    Sponsors and Collaborators

    • Istituto Oncologico Veneto IRCCS
    • Ministry of Health, Italy

    Investigators

    • Principal Investigator: Antonella Brunello, Istituto Oncologico Veneto

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Istituto Oncologico Veneto IRCCS
    ClinicalTrials.gov Identifier:
    NCT04656262
    Other Study ID Numbers:
    • IOV-2018-STS-METROPHOLYS
    First Posted:
    Dec 7, 2020
    Last Update Posted:
    Apr 1, 2022
    Last Verified:
    Mar 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 1, 2022