DOSAgE study: A multicenter randomized phase III trial of DOSe-reduced Chemotherapy for Advanced Colorectal Cancer in Older patients
- Conditions
- Metastatic Colorectal Cancer
- Registration Number
- 2023-506115-17-00
- Lead Sponsor
- Academisch Ziekenhuis Leiden
- Brief Summary
To demonstrate that upfront dose-reduced chemotherapy is non-inferior to full-dose treatment with regard to progression-free survival in patients with metastatic colorectal cancer, with a stratification for mono-chemotherapy versus doublet chemotherapy depending on individual risk of toxicity.
- Detailed Description
Treating older adults with chemotherapy remains a challenge, as they are strongly underrepresented in clinical trials and no robust guidelines for treating older patients exist. Moreover, older adults are at increased risk of chemotherapy-related toxicity, resulting in decreased quality of life (QoL), increased hospital admissions and high health care costs. Therefore, the aim of the DOSAGE study is to demonstrate that upfront dose-reduced chemotherapy in patients with metastasized colorectal cancer is non-inferior to full-dose treatment with regard to progression-free survival (PFS). Treatment plans (monotherapy or doublet chemotherapy) will be based on expected risk of treatment toxicity for the individual patient (according to the Geriatric 8 (G8) questionnaire). The investigators expect that this treatment strategy will lead to less grade ≥3 toxicity, less early treatment continuation and hospitalizations and a better QoL and physical functioning.
The DOSAGE study is a phase III, open-label, non-inferiority, randomized controlled clinical trial in patients aged ≥70 years with metastasized colorectal cancer eligible for palliative chemotherapy. All participating patients will undergo geriatric screening by the G8 questionnaire and will be classified as "low risk of toxicity" (G8-score of 15 or higher) or "high risk of toxicity" (G8-score of 14 or lower or judged as "high toxicity risk" by their treating oncologist). Patients classified as low risk will be randomized between a fluoropyrimidine and oxaliplatin in either full-dose, or with an upfront dose-reduction of 25%. Patients classified as high risk will be randomized between fluoropyrimidine monotherapy in either full-dose or upfront dose-reduction. Addition of targeted treatment (bevacizumab or epidermal growth factor receptor (EGFR) inhibition) is allowed. Patients with a moderate renal impairment (GFR 30- 50 mL/min) will be treated with 25% reduced starting dose of capecitabine when randomized for full dose treatment and treated with 40% reduced starting dose when randomized for upfront dose reduction.
Primary outcome is PFS. Secondary endpoints include grade ≥3 toxicity, QoL, physical functioning, overall survival, number of treatment cycles, dose reductions, hospital admissions, cumulative received dosage and cost-effectiveness. Given a non-inferiority margin of 8 weeks, 587 patients will be included (293/292 patients per arm).
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 587
Patients aged 70 years or older with colorectal cancer and distant metastases without localized treatment options.
Patients who are candidates for first-line palliative chemotherapy as judged by their treating oncologist
Being able to understand the Dutch language
Written informed consent
Adequate bone marrow and organ function as defined by following laboratory values: Absolute neutrophil count (ANC) > 1.5 x 10^9 mmol/L, Hemoglobin (Hb) > 6.0 mmol/L, Platelets >100 x 109 / L, Serum bilirubin ≤ 2 x upper limit of normal (ULN), serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases.
Patients who received prior palliative chemotherapy
Patients in whom local treatment of metastases with curative intent is scheduled (i.e. liver surgery or stereotactic radiotherapy)
Patients who received prior adjuvant chemotherapy in the one year before inclusion in the study (chemotherapy before that time is allowed)
Patients with complete or incomplete dihydropyrimidine dehydrogenase (DPD) deficiency
Patients with Microsatellite instable (MSI)-high colorectal cancer
Patients with known HIV or active hepatitis infection
Patients with severe kidney failure (defined as GFR ≤30ml/min)
Patients with severe cognitive deficits making informed consent not possible
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival Progression-free survival
- Secondary Outcome Measures
Name Time Method Quality of Life Quality of Life
Physical Functioning Physical Functioning
Grade 3-5 chemotherapy-related toxicity Grade 3-5 chemotherapy-related toxicity
Overall Survival Overall Survival
Number of completed treatment cycles Number of completed treatment cycles
Dose reductions during treatment Dose reductions during treatment
Unplanned hospitalizations Unplanned hospitalizations
Cumulative received dosage Cumulative received dosage
Cost-effectiveness Cost-effectiveness
Trial Locations
- Locations (45)
Laurentius Ziekenhuis Roermond
🇳🇱Roermond, Netherlands
Stichting Viecuri Medisch Centrum voor Noord-Limburg
🇳🇱Venlo, Netherlands
Medisch Centrum Leeuwarden B.V.
🇳🇱Leeuwarden, Netherlands
Amsterdam UMC Stichting
🇳🇱Amsterdam, Netherlands
Sint Franciscus Vlietland Groep Stichting
🇳🇱Schiedam, Netherlands
Isala Klinieken Stichting
🇳🇱Zwolle, Netherlands
Noordwest Ziekenhuisgroep Stichting
🇳🇱Alkmaar, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Catharina Ziekenhuis Stichting
🇳🇱Eindhoven, Netherlands
ZorgSaam Ziekenhuis
🇳🇱Terneuzen, Netherlands
Scroll for more (35 remaining)Laurentius Ziekenhuis Roermond🇳🇱Roermond, NetherlandsLoes VerhoevenSite contact+3147538222loes.verhoeven@lzr.nl