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DOSAGE Study: Upfront Dose-Reduced Chemotherapy in Older Patients with Metastatic Colorectal Cancer

ConditionsOlder PatientsColorectal CancerMetastatic CancerCandidates for Palliative Chemotherapy
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age70+
SponsorLeiden University Medical Center

About this trial

The goal of this phase III, open-label, non-inferiority randomized controlled clinical trial is compare upfront dose-reduced chemotherapy with the standard dose chemotherapy in older patients ( ≥70 years) with metastasized colorectal cancer, with regard to progression-free survival (PFS). The choice between monotherapy (a fluoropyrimidine) and doublet chemotherapy (a fluoropyrimidine with oxaliplatin) will be made for each individual patient based on expected risk of chemotherapy toxicity (according to the G8 screening). Patients classified as low risk of toxicity will be randomized between doublet chemotherapy in either full-dose, or with an upfront dose-reduction of 25%. Patients classified as high risk will be randomized between monotherapy in either full-dose or 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Adequate bone marrow and organ function: 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.

Disqualifiers

Patients who received prior palliative chemotherapy

Patients in whom local treatment of metastases is scheduled (i.e. liver surgery or stereotactic radiotherapy)

Candidates for triple chemotherapy

Patients who received prior adjuvant chemotherapy in the one year before inclusion in the study (chemotherapy before that time is allowed)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Doublet Chemotherapy, Standard Dose (100%)

    Drug

    Capecitabine 1000mg / m2 oral at day 1-14 (every 3 weeks) Oxaliplatin 130mg/m2 at day 1 (every 3 weeks) OR 5-FU 400mg/m2 IV bolus at day 1 followed by 2400mg/m2 in 46 hours (every 2 weeks) Leucovorin 400mg/m2 day 1 (every 2 weeks) Oxaliplatin 85mg/m2 day 1 (every 2 weeks)

  • Doublet Chemotherapy, Dose-reduced (75%)

    Drug

    75% of: Capecitabine 1000mg / m2 oral at day 1-14 (every 3 weeks) Oxaliplatin 130mg/m2 at day 1 (every 3 weeks) OR 5-FU 400mg/m2 IV bolus at day 1 followed by 2400mg/m2 in 46 hours (every 2 weeks) Leucovorin 400mg/m2 day 1 (every 2 weeks) Oxaliplatin 85mg/m2 day 1 (every 2 weeks)

  • Monotherapy, Standard Dose (100%)

    Drug

    \- Capecitabine 1000mg/m2 oral at day 1-14 (every 3 weeks)

  • Monotherapy, Dose-reduced (75%)

    Drug

    75% of: \- Capecitabine 1000mg/m2 oral at day 1-14 (every 3 weeks)

Treatment groups

587 Participants
are divided into 4 treatment groups
Group A: Doublet therapy, full dose (low toxicity risk based on G8)Active comparator 1 intervention
Group B: Doublet therapy, dose-reduced (low toxicity risk based on G8)Experimental treatment 1 intervention
Group C: Fluoropyrimidine monotherapy, full dose (high toxicity risk based on G8)Active comparator 1 intervention
Group D: Fluoropyrimidine monotherapy, dose-reduced (high toxicity risk based on G8)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Progression-Free Survival

Time frame
Time from randomization until either radiological or clinical progression or death, whichever occurs first, assessed up to at least one year.

Secondary outcomes

1

Quality of Life Questionnaire

Measured by EQ-5D questionnaire

Time frame
At 1, 3, 6 and 12 months after randomization
2

Quality of Life Questionnaire

Measured by EORTC Core QLQ-C30 questionnaire

Time frame
At 1, 3, 6 and 12 months after randomization
3

Physical functioning Questionnaire

Measured by Lawton-Instrumental Activities of Daily Living (IADL) questionnaire

Time frame
At 1, 3, 6 and 12 months after randomization
4

Physical functioning Questionnaire

Measured by Katz-Activities of Daily Living (ADL) questionnaire

Time frame
At 1, 3, 6 and 12 months after randomization

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Leiden University Medical Center

Lead sponsor

Dutch Colorectal Cancer Group

Collaborator

Source ClinicalTrials.gov
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