DOSAgE study: A multicenter randomized phase III trial of DOSe-reduced Chemotherapy for Advanced Colorectal Cancer in Older patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Oct 2024 → ongoing

Decision date (initial)

2024-05-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-506115-17-00

ClinicalTrials.gov

NCT06275958

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

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.

Secondary objectives 7

1. To determine whether upfront dose reduction of chemotherapy improves QoL and physical functioning
2. To determine whether upfront dose reduction of chemotherapy reduces grade 3-5 toxicity
3. To study whether upfront dose reduction is non-inferior to full-dose treatment with regard to overall survival
4. To determine whether upfront dose reduction leads to more treatment completion, less dose reductions and lower unplanned hospital admission rates
5. To study whether upfront dose reduction lead to an increase in received cumulative dosage, and to estimate whether this is associated with PFS
6. To identify predictive geriatric markers of poor outcomes using a geriatric assessment
7. To study whether upfront dose reduction is cost-effective

Conditions and MedDRA coding

Metastatic Colorectal Cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Dutch Cancer Society, Leids Universitair Medisch Centrum (LUMC)

Plan to share IPD

No

IPD plan description

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients aged 70 years or older with colorectal cancer and distant metastases without localized treatment options.
2. Patients who are candidates for first-line palliative chemotherapy as judged by their treating oncologist
3. Being able to understand the Dutch language
4. Written informed consent
5. 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.

Exclusion criteria 8

1. Patients who received prior palliative chemotherapy
2. Patients in whom local treatment of metastases with curative intent is scheduled (i.e. liver surgery or stereotactic radiotherapy)
3. Patients who received prior adjuvant chemotherapy in the one year before inclusion in the study (chemotherapy before that time is allowed)
4. Patients with complete or incomplete dihydropyrimidine dehydrogenase (DPD) deficiency
5. Patients with Microsatellite instable (MSI)-high colorectal cancer
6. Patients with known HIV or active hepatitis infection
7. Patients with severe kidney failure (defined as GFR ≤30ml/min)
8. Patients with severe cognitive deficits making informed consent not possible

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival

Secondary endpoints 9

1. Quality of Life
2. Physical Functioning
3. Grade 3-5 chemotherapy-related toxicity
4. Overall Survival
5. Number of completed treatment cycles
6. Dose reductions during treatment
7. Unplanned hospitalizations
8. Cumulative received dosage
9. Cost-effectiveness

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Johanneke Portielje

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Johanneke Portielje

Locations

1 EU/EEA country · 45 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications