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

NCT04656262 | Terminated Phase 3

• 1 other identifier: IOV-2018-STS-METROPHOLYS
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 13

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.

Conditions

Soft Tissue Sarcoma Adult

Outcome Measures

Primary Outcomes (1)

• 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

  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 (3)

• 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

• Overall survival

  Time from randomization to the date of death due to any cause or last follow up assessed up to 12 months

• Overall Toxicity Rate

  From signing IC until 30 days after last study treatment

Study Arms (2)

Metronomic cyclophosphamide

EXPERIMENTAL

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

Doxorubicin

ACTIVE COMPARATOR

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

Interventions

Cyclophosphamide DRUG

Cyclophosphamide is formulated as coated tablets of 50mg for oral administration

Also known as: Endoxan

Metronomic cyclophosphamide

Doxorubicin DRUG

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

Doxorubicin

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• Ministry of Health, Italy: collaborator

Study Sites (13)

Policlinico Sant'Orsola Malpighi

Bologna, BO, 40138, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Istituto Ortopedico Rizzoli IRCCS

Bologna, 40136, Italy

Location

Fondazione del Piemonte per l'Oncologia IRCCS

Candiolo, 10060, Italy

Location

IRST Romagnolo IRCCS

Meldola, 47014, Italy

Location

Istituto Nazionale Tumori IRCCS

Milan, 20133, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

AOU Policlinico Giaccone Palermo

Palermo, 90127, Italy

Location

Ospedale Misericordia e Dolce

Prato, 59100, Italy

Location

Policlinico Universitario Campus Biomedico

Roma, 00128, Italy

Location

IFO - Istituto Regina Elena

Roma, 00144, Italy

Location

Presidio Sanitario Humanitas - Gradenico

Torino, 10153, Italy

Location

AOUI Policlinico Borgo Roma

Verona, 37134, Italy

Location

MeSH Terms

Interventions

Cyclophosphamide; Doxorubicin

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Antonella Brunello

  Istituto Oncologico Veneto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 7, 2020
• Study Start: September 10, 2018
• Primary Completion: May 23, 2024
• Study Completion: May 23, 2024
• Last Updated: July 8, 2024

Record last verified: 2024-07

Locations

IT (13)