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Older PatientsPhase 3DOSAGENCT06275958

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

A Phase 3 study testing Doublet Chemotherapy, Standard Dose (100%), Doublet Chemotherapy, Dose-reduced (75%) and Monotherapy, Standard Dose (100%) in people with Older Patients and Colorectal Cancer, run by Leiden University Medical Center at 36 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 70 years and older
What is being tested?
Doublet Chemotherapy, Standard Dose (100%), Doublet Chemotherapy, Dose-reduced (75%) and Monotherapy, Standard Dose (100%)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
587 participants
Where
36 sitesNetherlands
Study dates
1 Jul 2024to Dec 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
  • Patients with complete or incomplete dihydropyrimidine dehydrogenase (DPD) deficiency
  • Patients with Microsatellite instable (MSI)-high colorectal cancer
Show all 9Show fewer
  • Patients with HIV or active hepatitis
  • Patients with severe kidney failure (defined as GFR ≤30ml/min)
  • Patients with severe cognitive deficits making informed consent not possible

Trial locations and contacts

36 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Joosje Baltussen contact

071 - 526 35 23

DOSAGE@lumc.nl

Data Management: Clinical Research Center LUMC contact

ClinicalResearchCenter@lumc.nl

36 sites in 1 country

Netherlands36 sites, 36 recruiting

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch

    Not yet recruiting

  • Noordwest Ziekenhuisgroep

    Alkmaar

    Not yet recruiting

  • Ziekenhuis Amstelland

    Amstelveen

    Not yet recruiting

  • Amsterdam UMC

    Amsterdam

    Not yet recruiting

  • Rijnstate

    Arnhem

    Not yet recruiting

  • Wilhelmina Ziekenhuis

    Assen

    Not yet recruiting

  • Rode Kruis Ziekenhuis

    Beverwijk

    Not yet recruiting

  • Slingeland Ziekenhuis

    Doetinchem

    Not yet recruiting

  • Ziekenhuis Gelderse Vallei

    Ede

    Not yet recruiting

  • Catharina Ziekenhuis

    Eindhoven

    Recruiting

  • Treant

    Emmen

    Not yet recruiting

  • Admiraal de Ruyter Ziekenhuis

    Goes

    Not yet recruiting

  • Beatrixziekenhuis

    Gorinchem

    Not yet recruiting

  • Groene Hart Ziekenhuis

    Gouda

    Recruiting

  • Saxenburgh

    Hardenberg

    Not yet recruiting

  • St. Jansdal Ziekenhuis

    Harderwijk

    Not yet recruiting

  • Elkerliek Ziekenhuis

    Helmond

    Recruiting

  • Tergooi MC

    Hilversum

    Recruiting

  • Medisch Centrum Leeuwarden

    Leeuwarden

    Not yet recruiting

  • Leiden University Medical Center

    Leiden

    Recruiting

  • Alrijne Ziekenhuis

    Leiderdorp

    Not yet recruiting

  • Canisius Wilhelmina Ziekenhuis

    Nijmegen

    Not yet recruiting

  • Laurentius Ziekenhuis

    Roermond

    Not yet recruiting

  • Bravis ziekenhuis

    Roosendaal

    Recruiting

  • Ikazia Ziekenhuis

    Rotterdam

    Recruiting

  • Maasstad Ziekenhuis

    Rotterdam

    Not yet recruiting

  • Ommelander Ziekenhuis

    Scheemda

    Not yet recruiting

  • ZorgSaam Zorggroep Zeeuws-Vlaanderen

    Terneuzen

    Recruiting

  • Haaglanden Medisch Centrum

    The Hague

    Not yet recruiting

  • Hagaziekenhuis

    The Hague

    Recruiting

  • Bernhoven

    Uden

    Not yet recruiting

  • Diakonessenhuis

    Utrecht

    Not yet recruiting

  • St Antonius

    Utrecht

    Not yet recruiting

  • VieCuri Medisch Centrum

    Venlo

    Not yet recruiting

  • Streekziekenhuis Koninging Beatrix

    Winterswijk

    Recruiting

  • Zaans Medisch Centrum

    Zaandam

    Not yet recruiting

Other trials in Netherlands

About this study

Official title: DOSAGE Study: a Multicenter Randomized Phase III Trial of DOSe-reduced Chemotherapy for Advanced Colorectal Cancer in Older Patients

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.

Read the 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).

Being tested
Doublet Chemotherapy, Standard Dose (100%), Doublet Chemotherapy, Dose-reduced (75%), Monotherapy, Standard Dose (100%), Monotherapy, Dose-reduced (75%)
Keywords
Dose-reduced Chemotherapy, Upfront Reduction, Palliative Chemotherapy, Non-inferiority
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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)
Study groups in NCT06275958
Study groupRoleWhat they receive
Doublet therapy, full dose (low toxicity risk based on G8)Active comparatorLow risk of toxicity: G8-score of 15 or higher
Receives: Drug: Doublet Chemotherapy, Standard Dose (100%)
Doublet therapy, dose-reduced (low toxicity risk based on G8)ExperimentalLow risk of toxicity: G8-score of 15 or higher
Receives: Drug: Doublet Chemotherapy, Dose-reduced (75%)
Fluoropyrimidine monotherapy, full dose (high toxicity risk based on G8)Active comparatorHigh risk of toxicity: G8-score of 14 or lower or judged as "high toxicity risk" by their treating oncologist
Receives: Drug: Monotherapy, Standard Dose (100%)
Fluoropyrimidine monotherapy, dose-reduced (high toxicity risk based on G8)ExperimentalHigh risk of toxicity: G8-score of 14 or lower or judged as "high toxicity risk" by their treating oncologist
Receives: Drug: Monotherapy, Dose-reduced (75%)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival

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

Secondary outcomes (12)

  1. Quality of Life Questionnaire

    Measured by EQ-5D questionnaire

    Measured: At 1, 3, 6 and 12 months after randomization

  2. Quality of Life Questionnaire

    Measured by EORTC Core QLQ-C30 questionnaire

    Measured: At 1, 3, 6 and 12 months after randomization

  3. Physical functioning Questionnaire

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

    Measured: At 1, 3, 6 and 12 months after randomization

  4. Physical functioning Questionnaire

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

    Measured: At 1, 3, 6 and 12 months after randomization

  5. Grade 3-5 chemotherapy-related toxicity

    According to the CTCAE V5

    Measured: Through study duration, an average of 8 months

  6. Overall Survival

    Measured: Time between randomization until death, assessed up to at least one year.

  7. Number of completed treatment cycles

    Measured: Through study duration, an average of 8 months

  8. Dose reductions during treatment

    Defined as ≥25% reduction of the initial dosage

    Measured: Through study duration, an average of 8 months

  9. Dose delay during treatment

    Measured: Through study duration, an average of 8 months

  10. Unplanned hospitalizations

    Measured: The first year after treatment initiation

  11. Cumulative received dosage

    Adjusted for BSA

    Measured: Through study duration, an average of 8 months

  12. Cost-effectiveness

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2024
  2. Study start1 Jul 2024
  3. Primary completionJun 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

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
Model description
A phase III, open-label, non-inferiority, randomized controlled clinical trial comparing dose-reduced chemotherapy versus standard dose chemotherapy in older adults with metastasized colorectal cancer
Masking
None (open label)
Enrolment
587 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06275958
Sponsor's protocol ID
2023-506115-17
Other IDs
2023-506115-17, 2023
Acronym
DOSAGE
Status last verified
Oct 2024
First submitted
6 Feb 2024
Last updated
16 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Which parts of your data(sets) will you select for publication? The datasets generated during and/or analysed during the study will not be publicly available due to participant privacy but will be available from the corresponding author on reasonable request Are there any restrictions placed on sharing/reuse of some/all of your data due to one or more of the following options? Signed informed consent Research agreement Will you publish your data open access or with restricted access? Restricted access Publishing your data (partly) with 'restricted access': what is the reason for this? Data contains privacy-sensitive information Contractual obligations Reuse by third-party through DSA. Where will you publish your (meta)data? I will not publish (meta)data outside the LUMC

Publications

  • Baltussen JC, van den Bos F, Slingerland M, Binda TRR, Liefers GJ, van den Hout WB, Fiocco M, Verschoor AJ, Cloos-van Balen M, Holterhues C, Houtsma D, Jochems A, Spierings LEAMM, van Bodegom-Vos L, Mooijaart SP, Gelderblom H, Speetjens FM, de Glas NA, Portielje JEA. DOSAGE study: protocol for a phase III non-inferiority randomised trial investigating dose-reduced chemotherapy for advanced colorectal cancer in older patients. BMJ Open. 2024 Aug 13;14(8):e089882. doi: 10.1136/bmjopen-2024-089882.

    PubMed 39142680

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Doublet Chemotherapy, Standard Dose (100%), Doublet Chemotherapy, Dose-reduced (75%) and Monotherapy, Standard Dose (100%) in people with Older Patients and Colorectal Cancer, run by Leiden University Medical Center at 36 sites in Netherlands.

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 4 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in Netherlands. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Joosje Baltussen (071 - 526 35 23, DOSAGE@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06275958, which also lists 1 linked publication.

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 16 Oct 2024.

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