Advanced Soft-tissue SarcomaPhase 3ToleranceNCT04780464
A 3 Arm Randomized Study on Health-related QoL of Elderly Patients With Advanced Soft Tissue Sarcoma
A Phase 3 study testing Doxorubicin, Cyclophosphamide Oral Product and Prednisolone in people with Advanced Soft-tissue Sarcoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Advanced Soft-tissue Sarcoma
- What is being tested?
- Doxorubicin, Cyclophosphamide Oral Product and Prednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 11 Apr 2022to 11 Nov 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
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- 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);
- Hepatic function: bilirubin ≤ 1.0 x ULN of institutional limits, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤1.5 x ULN.
- If isolated elevated bilirubin <2 x ULN and Gilberts syndrome suspected, suggest repeating bloods after food. If bilirubin improves to meet the criteria above this is acceptable. More severe persistent hepatic impairment of whatever cause would exclude the patient from treatment till resolved.
- Cardiac function: clinically normal function based on the institutional lower limit of normal for left ventricular ejection fraction (LVEF) as assessed either by multi-gated acquisition scan (MUGA) or cardiac ultrasound and 12 lead electrocardiogram (ECG) without clinically relevant abnormalities. Measurement should include investigator assessment of a potential participant's risk for heart failure with a validated clinical classification system, i.e. the New York Heart Association Functional Classification. Only patients with NYHA class 1 and 2 according to appendix D are eligible.
- Completion of EORTC QLQ-C30 and EORTC QLQ-ELD14 at baseline.
- Assessment of G8 geriatric screening tool
- Assessment of Katz Index of Independence in Activities of Daily Living (ADL)
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
- With female partners of childbearing potential, men must remain abstinent or use a condom during the treatment period and for a period of 6 months after the last dose of doxorubicin-based chemotherapy and for a period of 12 months after the last dose of cyclophosphamide-based chemotherapy. Men must refrain from donating sperm during this same period. Contraception should be considered for the female partners of childbearing potential as well.
- With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for a period of 6 months after the last dose of doxorubicin-based chemotherapy and for a period of 12 months after the last dose of cyclophosphamide-based chemotherapy to avoid exposing the embryo.
- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations including commitment to completing questionnaires during the course of the study.
Who cannot join
- 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
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- 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
- Bone marrow aplasia
- Psychosis
- Active or uncontrolled infections among which those requiring systemic antibiotics or antimicrobial therapy.
- Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
- Vaccination with live vaccines within 30 days prior to study entry
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
- Known contraindication to imaging tracer or contrast medium and contraindication to MRI
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and its active requirements (including completion of questionnaires) and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: a 3 Arm Randomized Study on Health-related Quality of Life of Elderly Patients With Advanced Soft Tissue Sarcoma Undergoing Doxorubicin Alone Every Three Weeks or Doxorubicin Weekly or Cyclophosphamide Plus Predniso(lo)ne Treatment
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).
Read more
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
- Being tested
- Doxorubicin, Cyclophosphamide Oral Product, Prednisolone, Prednisone
- Keywords
- Quality of Life, Elderly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Also called Adriamycin;
60 to 75 mg/m² intravenous, every 3 weeks for max 6 cycles until PD
DoxorubicinDrug
Also called Adriamycin;
12 mg/m2 intravenous weekly for a maximum of 450 mg/m2 until PD
Cyclophosphamide Oral ProductDrug
100 mg BD on day 1 to day 7 of each 14 day cycle until PD
PrednisoloneDrug
10-20 mg on day 1 to day 7 of each 14 day cycle until PD
PrednisoneDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Standard doxorubicin | Active comparator | Not described Receives: Drug: Doxorubicin |
| Metronomic doxorubicin | Experimental | Not described Receives: Drug: Doxorubicin |
| Metronomic oral cyclophosphamide + prednisolone or prednisone | Experimental | Not described Receives: Drug: Cyclophosphamide Oral Product; Drug: Prednisolone; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health-related Quality of Life
Difference in physical and role functioning at 12 weeks
Measured: 4 years after first patient in
Secondary outcomes (3)
Tumour response
tumor response according to RECIST criteria (version 1.1)
Measured: 5.5 years after first patient in
Progression-free-survival
Progression-free-survival from the date of randomization to the date of first progression or death, whatever comes first
Measured: 5.5 years after first patient in
Overall survival
Overall survival from the date of randomization to the date of death, whatever the cause
Measured: 5.5 years after first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start11 Apr 2022
- Primary completion22 Sep 2023
- Study completion11 Nov 2023
Why it stopped: Withdrawal grant provider
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Soft-tissue SarcomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Winette van der Graaf, Study chair, Nationaal Kanker Instituut, Amsterdam, NL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04780464
- Sponsor's protocol ID
- EORTC-1976-STBSG
- Other IDs
- 2021-000125-27
- Acronym
- Tolerance
- Status last verified
- Feb 2024
- First submitted
- 2 Mar 2021
- Last updated
- 22 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- a 3 Arm Randomized Study on Health-related Quality of Life of Elderly Patients With Advanced Soft Tissue Sarcoma Undergoing Doxorubicin Alone Every Three Weeks or Doxorubicin Weekly or Cyclophosphamide Plus Predniso(lo)ne Treatment
- ClinicalTrials.gov ID
- NCT04780464
- Acronym / sponsor ID
- Tolerance / EORTC-1976-STBSG
- Conditions
- Advanced Soft-tissue Sarcoma
- Keywords
- Quality of Life, Elderly
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawal grant provider
- Enrolment
- 14 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- 11 Apr 2022 (actual)
- Primary completion
- 22 Sep 2023 (actual)
- Study completion
- 11 Nov 2023 (actual)
- First posted
- 3 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxorubicinAlso: Adriamycin;60 to 75 mg/m² intravenous, every 3 weeks for max 6 cycles until PD | Drug | Standard doxorubicin |
| DoxorubicinAlso: Adriamycin;12 mg/m2 intravenous weekly for a maximum of 450 mg/m2 until PD | Drug | Metronomic doxorubicin |
| Cyclophosphamide Oral Product100 mg BD on day 1 to day 7 of each 14 day cycle until PD | Drug | Metronomic oral cyclophosphamide + prednisolone or prednisone |
| Prednisolone10-20 mg on day 1 to day 7 of each 14 day cycle until PD | Drug | Metronomic oral cyclophosphamide + prednisolone or prednisone |
| Prednisone10-20 mg on day 1 to day 7 of each 14 day cycle until PD for those Countries where Prednisolone in tablets is not available | Drug | Metronomic oral cyclophosphamide + prednisolone or prednisone |
Primary outcome
Health-related Quality of Life
Time frame: 4 years after first patient in
Difference in physical and role functioning at 12 weeks
3 secondary outcomes
Tumour response
Time frame: 5.5 years after first patient in
Progression-free-survival
Time frame: 5.5 years after first patient in
Overall survival
Time frame: 5.5 years after first patient in
Results and safety
The study was stopped early (reason given: Withdrawal grant provider). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Winette van der Graaf study chair
Nationaal Kanker Instituut, Amsterdam, NL
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxorubicin, Cyclophosphamide Oral Product and Prednisolone in people with Advanced Soft-tissue Sarcoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Cyprus, Jordan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Withdrawal grant provider). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health-related Quality of Life (time frame: 4 years after first patient in). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.