A 3 Arm Randomized Study on Health-related QoL of Elderly Patients With Advanced Soft Tissue Sarcoma

NCT04780464 | Terminated Phase 3 DMC

• 2 other identifiers: EORTC-1976-STBSG2021-000125-27
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a multi-centre, open label, randomized phase 3 selection study (1:2:2 randomization). After confirmation of the eligibility criteria, 185 patients will be randomized 1:2:2 to either the control arm (doxorubicin 60-75 mg/m² IV every 3 weeks) or experimental arm 1 (doxorubicin 12 mg/m2 IV every week) or experimental arm 2 (cyclophosphamide 100 mg orally BD plus prednisolone 10-20 mg orally on day 1 to day 7 of each 14 day cycle). HRQoL assessment will be performed every 3 weeks during the first 12 weeks and every 12 weeks thereafter until month 12 after start of treatment. Disease evaluation will be performed every 12 weeks until progression. The primary endpoint of the study is difference among the study arms in physical and role functioning at 12 weeks.

Conditions

Advanced Soft-tissue Sarcoma

Keywords

Quality of Life; Elderly

Outcome Measures

Primary Outcomes (1)

• Health-related Quality of Life

  Difference in physical and role functioning at 12 weeks

  4 years after first patient in

Secondary Outcomes (3)

• Tumour response

  5.5 years after first patient in

• Progression-free-survival

  5.5 years after first patient in

• Overall survival

  5.5 years after first patient in

Study Arms (3)

Standard doxorubicin

ACTIVE COMPARATOR

Drug: Doxorubicin

Metronomic doxorubicin

EXPERIMENTAL

Drug: Doxorubicin

Metronomic oral cyclophosphamide + prednisolone or prednisone

EXPERIMENTAL

Drug: Cyclophosphamide Oral Product; Drug: Prednisolone; Drug: Prednisone

Interventions

Doxorubicin DRUG

60 to 75 mg/m² intravenous, every 3 weeks for max 6 cycles until PD

Also known as: Adriamycin;

Standard doxorubicin

Cyclophosphamide Oral Product DRUG

100 mg BD on day 1 to day 7 of each 14 day cycle until PD

Metronomic oral cyclophosphamide + prednisolone or prednisone

Prednisolone DRUG

10-20 mg on day 1 to day 7 of each 14 day cycle until PD

Metronomic oral cyclophosphamide + prednisolone or prednisone

Prednisone DRUG

10-20 mg on day 1 to day 7 of each 14 day cycle until PD for those Countries where Prednisolone in tablets is not available

Metronomic oral cyclophosphamide + prednisolone or prednisone

Eligibility Criteria

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

You may qualify if:

• Histologically proven advanced unresectable or metastatic soft tissue sarcoma
• Representative formalin fixed, paraffin embedded tumor blocks or a minimum of 10 unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. Histological central review is not required before treatment start but it is mandatory to send at least 10 unstained tumor slides (blocks optional) at time of study entry. Local histopathological diagnosis will be accepted for entry into this trial.
• Age ≥ 65 years of age (patients between 65 and 69 years old are eligible if G8 score ≤ 14; patients ≥ 70 years old are eligible independent of G8 score)
• WHO performance status 0 - 2
• Life expectancy based on other significant morbidity of ≥ 6 months
• Presence of measurable disease (according to RECIST 1.1), as confirmed by imaging within the 28 days prior to randomization. CT with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT + MRI.
• Progressive disease at entry based on RECIST 1.1
• Patients amenable to receive doxorubicin according to investigator's assessment
• Adequate haematological and organ function assessed prior to randomization:
• Haematological function:
• haemoglobin ≥ 9.0 g/dL or 5.6 mmol/L
• absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• platelet count ≥ 100 x 109/L
• Coagulation: partial thromboplastin time (PTT) ≤ 1.0 times upper limit of normal (1.0 x ULN) of institutional limits and prothrombin time (PT) ≤ 1.0 x ULN of institutional limits
• Renal function: estimated glomerular filtration rate (eGFR) \> 50 ml/min/m2 (calculated by the MDRD formula in appendix E); no proteinuria ≥ grade 2 (CTCAE version 5.0);

You may not qualify if:

• Symptomatic or known brain metastasis
• Any prior treatment with anthracyclines
• Any prior systemic treatment for metastatic STS
• Inability to swallow and/ or retain oral tablets
• Rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
• Hypersensitivity to doxorubicin, cyclophosphamide, prednisolone or to any of their metabolites or to any of their excipients
• Uncontrolled severe illness, including but not limited to:
• Congestive heart failure
• Angina pectoris
• Acute inflammatory heart disease
• Myocardial infarction within 1 year before randomization
• Arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy
• Uncontrolled cardiac arrhythmia
• Increased haemorragic tendency
• Uncontrolled diabetes

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (2)

Bank Of Cyprus Oncology Centre

Nicosia, 2006, Cyprus

Location

King Hussein Cancer Center

Amman, 11941, Jordan

Location

MeSH Terms

Interventions

Doxorubicin; Prednisolone; Prednisone

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols

Study Officials

• Winette van der Graaf

  Nationaal Kanker Instituut, Amsterdam, NL

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 3, 2021
• Study Start: April 11, 2022
• Primary Completion: September 22, 2023
• Study Completion: November 11, 2023
• Last Updated: February 22, 2024

Record last verified: 2024-02

Locations

JO (1); CY (1)