Clinical trial NCT04656262: Low Dose Continuous Cyclophosphamide vs Standard Doxorubicin in Advanced Sarcoma Elderly Patients
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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Soft Tissue Sarcoma Adult
Lead sponsor: Istituto Oncologico Veneto IRCCS
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Italy
First posted: 2020-12-07
Enrollment: 79
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Time to treatment failure
timeFrame: 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 outcomes:
measure: Progression free Survival
timeFrame: 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
measure: Overall survival
timeFrame: Time from randomization to the date of death due to any cause or last follow up assessed up to 12 months
measure: Overall Toxicity Rate
timeFrame: From signing IC until 30 days after last study treatment
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
state: BO
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli IRCCS
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia IRCCS
city: Meldola
country: Italy
facility: IRST Romagnolo IRCCS
city: Milano
country: Italy
facility: Istituto Nazionale Tumori IRCCS
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Palermo
country: Italy
facility: AOU Policlinico Giaccone Palermo
city: Prato
country: Italy
facility: Ospedale Misericordia e Dolce
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Roma
country: Italy
facility: IFO - Istituto Regina Elena
city: Torino
country: Italy
facility: Presidio Sanitario Humanitas - Gradenico
city: Verona
country: Italy
facility: AOUI Policlinico Borgo Roma
Study officials:
affiliation: Istituto Oncologico Veneto
name: Antonella Brunello
role: PRINCIPAL_INVESTIGATOR
References: