Comparison of Oral Cyclophosphamide vs Doxorubicin in ≥65 Years Old Advanced or Metastatic Soft Tissue Sarcoma Patients

NCT04757337 | Recruiting Phase 3 DMC

• 2 other identifiers: UC-0103/18022018-000542-20
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

Most advanced or metastatic soft tissue sarcoma (STS) are unfortunately incurable, making the preservation of the patient's quality of life a major goal, along with prolonging survival. Age is not a criterion for not providing effective treatment, but the goals of treatment change with age and must be integrated into the treatment decision. Elderly patients prioritise a life free of dependency, preservation of their cognitive functions and quality of life related to their state of health. They are therefore reluctant to receive a treatment that does little to improve life expectancy at the cost of significant functional losses. Patients aged 65 years and older account for one third of all patients with STS. In the absence of dedicated recommendations, these elderly patients are currently receiving doxorubicin-based chemotherapy as first-line treatment (as recommended for younger patients), with a substantial risk of toxicity (especially cardiac). In this specific population, previous studies have shown that oral cyclophosphamide seems to have a promising activity, but also a very acceptable toxicity. Thus, the GERICO study aims to compare standard doxorubicin chemotherapy with oral cyclophosphamide for the treatment of elderly patients with STS.

Conditions

Advanced Soft-tissue Sarcoma; Metastatic Soft-tissue Sarcoma

Keywords

Elderly; older patients; oral cyclophosphamide; doxorubicin

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

  From randomization to disease progression or death, up to 2 years.

Secondary Outcomes (7)

• Overall survival (OS)

  From randomization to death from any cause, up to 2 years

• Best response under treatment

  From randomization to progression, death or new treatment, up to 2 years.

• Quality of life questionnaire - Core 30 (QLQ-C30)

  At baseline, week 9, week 18, 3 months, 6 months, 9 months, 12 months, 15 month, 18 month, and 24 months

• Quality of life questionnaire - Elderly cancer patients (QLQ-ELD14)

  At baseline, week 9, week 18, 3 months, 6 months, 9 months, 12 months, 15 month, 18 month, and 24 months

• Assessment of the toxicity profile of oral cyclophosphamide and doxorubicin, as per NCI CTCAE v5.0

  From randomization to progression, death or new treatment, up to 2 years.

Study Arms (2)

Doxorubicin

ACTIVE COMPARATOR

Intravenous Doxorubicin 60 mg/m² Cycle 1 then 75 mg/m² Cycle 2 to Cycle 6 D1-D21 with granulocyte-colony stimulating factor (G-CSF) and dexrazoxane.

Drug: Doxorubicin

Cyclophosphamide

EXPERIMENTAL

Cyclophosphamide per os 100 mg twice a day, 1 week on, 1 week off until 2 years, or unacceptable toxicity, disease progression, withdrawn of consent or death.

Drug: Cyclophosphamide

Interventions

Doxorubicin DRUG

6 x 3-week cycles corresponding to a maximal duration of 18 weeks

Doxorubicin

Cyclophosphamide DRUG

Until progression up to 24 months

Also known as: Endoxan®

Cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trust person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent
• Diagnosis of soft-tissue sarcoma histologically confirmed by Réseau de Référence en Pathologie des Sarcomes et des Viscères (RRePS)
• Metastatic or locally advanced disease not amenable to surgery, radiation, or combined modality treatment with curative intent. Palliative radiation therapy is permitted only if direct on nontarget lesion
• Documentation of disease progression within the last 6 months before randomization
• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT-scan as defined by response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)
• Life expectancy of at least 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• G8 score \>14
• Left ventricular ejection fraction (LVEF) value by echocardiogram or Multiple gated acquisition scanning (MUGA) ≥55%
• Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation:
• Absolute neutrophil count (ANC) ≥1,500/mm³
• Platelets ≥100,000/mm³
• Hemoglobin ≥9.0 g/dL
• Serum creatinine ≤2 x upper limit of normal (ULN)
• Glomerular filtration rate (GFR) ≥50 ml/min/1.73m² (calculated with MDRD)

You may not qualify if:

• Previous systemic treatment for advance or metastatic sarcoma
• Previous neoadjuvant or adjuvant anthracycline treatment for localized sarcoma
• Soft-tissue sarcoma with the following histological subtypes: dermatofibrosarcoma protuberans, desmoid tumor, alveolar or embryonal rhabdomyosarcoma, Desmoplastic small round cell tumor, Kaposi Sarcoma, Gastro-Intestinal stromal tumor, Peripheral neuroectodermal tumors
• Primary bone sarcoma (including osteosarcoma, Ewing tumor, chondrosarcoma, and chordoma)
• Symptomatic or known central nervous system (CNS) metastases
• Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator and history of radiotherapy mediastinal in the last five years
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before Day 1 of treatment
• Active cardio vascular disease including any of the following: Congestive heart failure (New York Heart Association (NYHA) ≥Class 2), unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), acute inflammatory cardiopathy, severe arrythmia, high risk of bleeding, cerebrovascular accident within the last 6 months
• Uncontrolled grade \>2 hypertension. (Systolic blood pressure ≥160 mmHg or diastolic pressure ≥100 mmHg despite optimal medical management)
• Ongoing infection ≥Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
• Known history of human immunodeficiency virus (HIV) infection
• Known history of chronic hepatitis B or C
• History of organ allograft
• Pre-existing acute hemorrhagic cystitis, urinary tract obstruction, acute urinary tract infection
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Institut Claudius Reagaud-IUCT Oncopôle

Toulouse, 31100, France

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Thibaud Valentin, M.D

  Institut Claudius Regaud-IUCT Oncopôle Toulouse

  PRINCIPAL INVESTIGATOR

• Olivier Mir, M.D

  Gustave Roussy Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thibaud Valentin, M.D

CONTACT

+33 5 31 15 51 70; Valentin.Thibaud@iuct-oncopole.fr

Meryem Brihoum

CONTACT

m-brihoum@unicancer.fr

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: February 10, 2021
• First Posted: February 17, 2021
• Study Start: June 18, 2021
• Primary Completion: July 1, 2025
• Study Completion: April 1, 2026
• Last Updated: March 25, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)