Main objectiveThe primary objective of this study is to assess whether a higher HRQoL, in terms of impact of the disease and its treatment on physical and role functioning, is achieved with metronomic schedules of doxorubicin or cyclophosphamide…
ID
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
• Difference in physical and role functioning at 12 weeks.
Physical functioning (PF) is one of the functional scale scores of the EORTC
QLQ-C30 questionnaire. The scale score is based on the mean score of 5 items
measuring patients' self-reported ability to perform physical activities. The
scale score can range from 0-100 with higher scores indicating better
functioning.
Role functioning (RF) is one of the other functional scale scores of the EORTC
QLQ-C30 questionnaire. The scale score is based on the mean score of 2 items
measuring patients' self-reported ability to perform daily tasks related to
household, work or recreation. The scale score can range from 0-100 with higher
scores indicating better functioning.
Secondary outcome
Secondary endpoints:
• Difference in all other EORTC QLQ-C30 scales at 12 weeks
• Sensitivity: Difference in physical and role functioning at 24 weeks
• Difference in progression free survival (PFS) at 12 weeks according to the
RECIST 1.1
• Efficacy: PFS, overall survival (OS), tumour response (RECIST 1.1)
• Safety: Adverse Events (AEs) according to CTCAE v5.0
• Tolerability: treatment discontinuation, delay and/or reduction.
Exploratory endpoints:
• Difference in ELD14 scales
• Difference in ADL scales
Background summary
Elderly patients 65 years or older with advanced STS are largely
underrepresented in clinical trials of first-line chemotherapy. Elderly
patients participating in clinical trials often have an excellent performance
status, which is not representative of an unselected *real-life* elderly STS
population. Therefore, treatment decisions in routine clinical practice are
hampered by the limited scientific evidence on the efficacy and toxicity of
doxorubicin and other chemotherapy regimes in elderly patients with advanced
STS. These findings provide rationale for the development of novel trials for
elderly patients taking into account patient-reported daily functioning and
incorporating GA as a measure of physiologic age.
Study objective
Main objective
The primary objective of this study is to assess whether a higher HRQoL, in
terms of impact of the disease and its treatment on physical and role
functioning, is achieved with metronomic schedules of doxorubicin or
cyclophosphamide plus predniso(lo)ne versus the standard doxorubicin treatment.
Secondary objectives:
• To assess whether there is an improvement in quality of life, in terms of
impact of the disease and its treatment on social, emotional and cognitive
functioning as well as self-reported symptoms and overall quality of
life/health perception, among patients treated with metronomic doxorubicin,
patients treated with metronomic cyclophosphamide plus predniso(lo)ne and
patients treated with standard doxorubicin regimen.
• To assess whether there is a difference in the progression free survival,
overall survival and tumour response among patients treated with metronomic
doxorubicin, patients treated with metronomic cyclophosphamide plus
predniso(lo)ne and patients treated with standard doxorubicin regimen.
• To assess the toxicity profile of the three treatment arms
• To assess the tolerability of the three treatment arms
Exploratory objectives:
• To assess whether there is a difference in quality of life, in terms of EORTC
QLQ-ELD14 scales, among patients treated with metronomic doxorubicin, patients
treated with metronomic cyclophosphamide plus predniso(lo)ne and patients
treated with standard doxorubicin regimen.
• To assess whether there is a difference in maintaining fundamental skills
that are required to care for oneself, as measured by the ADL (Activities of
Daily Living) tool, among patients treated with metronomic doxorubicin,
patients treated with metronomic cyclophosphamide plus predniso(lo)ne and
patients treated with standard doxorubicin regimen.
Study design
This is a multi-centre, open label, randomized phase 3 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 tablets 100 mg twice a day (morning and
evening) plus prednisolone/prednisone tablets 10 or 20 mg once a day (in the
morning), 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 1 year after start of treatment. Disease evaluation will be performed
every 12 weeks until progression.
Intervention
Experimental arm 1
Patients randomized to the experimental arm 1 will be treated with doxorubicin
12 mg/m2 administered weekly intravenously (bolus or short infusion as per
local standard practice) for a maximum of 450 mg/m2 until disease progression,
unacceptable toxicity, patient*s refusal or occurrence of concomitant disease
requiring intervention that interferes with the study treatment, whichever
comes first. Adequate antiemetic treatment, supportive measures and
hematopoietic growth factors should be delivered according to local treatment
standards.
Experimental arm 2
Patients randomized to the experimental arm 2 will be treated with oral
cyclophosphamide 100 mg BD (at approximately 8:00 and 19:00) plus
prednisolone/prednisone 10 or 20 mg daily (in the morning) on day 1 to day 7 of
each 14-day cycle until disease progression, unacceptable toxicity, patient*s
refusal or occurrence of concomitant disease requiring intervention that
interferes with the study treatment, whichever comes first.
Use of haematopoiesis stimulating agents (colony-stimulating factors and
erythropoiesis stimulating agents) may be considered to reduce the risk of
myelosuppressive complications and/or help facilitate the delivery of the
intended dosing.
Adequate amount of fluids (1.5 L- 2 L) should be ingested daily (or infused) to
force diuresis in order to reduce the risk of urinary tract toxicity.
Study burden and risks
- Possible side effects of chemotherapy treatment.
- Regular visits at the hospital including physical examinations, blood
withdrawal, Quality of Life questionnaires, biopsies (if archived material is
not available) and CT scans.
Avenue E. Mounierlaan 83/11
Brussel 1200
BE
Avenue E. Mounierlaan 83/11
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
• Histologically proven advanced unresectable or metastatic soft tissue sarcoma
(STS)
• Representative formalin fixed, paraffin embedded tumor blocks or slides,
either from the primary tumor or a metastatic lesion, must be available for
central review.
• 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
(protocol version 2.0; pages 22-23, section 4.1)
• Completion of EORTC QLQ-C30 and EORTC QLQ-ELD14.
• Assessment of G8 geriatric screening tool
• For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and agreement to refrain from
donating sperm, as defined in protocol version 2.0; pages 22-23; section 4.1)
• 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.
Exclusion criteria
• Gastrointestinal stromal tumors (GISTs)
• Symptomatic or known brain metastasis
• Any prior treatment with anthracyclines
• Any prior systemic treatment for metastatic STS
• Any prior, current or planned treatment with radiotherapy of head and neck,
thorax or liver
• Inability to swallow and/ or retain oral tablets
• Rare hereditary galactose intolerance, Lapp lactase deficiency or
glucose-galactose malabsorption
• Hypersensitivity to doxorubicin, cyclophosphamide, prednisolone, prednisone
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
- Severe osteoporosis
- Peptic ulcer
- 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.
• Known 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-000125-27-NL |
| ClinicalTrials.gov | NCT04780464 |
| CCMO | NL81448.041.22 |