Neoplasms

Digestive System Diseases

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Intestinal Neoplasms

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Intestinal Diseases

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Leucovorin

Fluorouracil

Levoleucovorin

Aflibercept

Oxaliplatin

Folic Acid

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients in the 5-FU / oxaliplatin arm receive modified (m) FOLFOX 7: Folinic acid 350 mg/m² and oxaliplatin 68 mg/m² by concurrent 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion every 2 weeks (qd15).

This regimen represents the 80% dosage reduced mFOLFOX 7. The 80% dose reduction was shown to be a tolerable regimen in frail elderly patients in the FOCUS 2 study.

Patients in the 5-FU / aflibercept arm receive aflibercept 4mg/kg as 1-h infusion followed by folinic acid 350 mg/m² by 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion (mLV5FU2) every 2 weeks (qd15).

The decision to use reduced doses of 5-FU and folinic acid was made to have comparable doses to the reduced FOLFOX 7.

Patients receive aflibercept 4mg/kg as 1-h infusion followed by folinic acid 350 mg/m² by 2-h intravenous infusion, 5-fluorouracil 1920 mg/m² 46-h intravenous infusion (mLV5FU2) every 2 weeks (qd15).

Aflibercept + mLV5FU2

Patients in this arm receive modified (m) FOLFOX 7: Folinic acid 350 mg/m² and oxaliplatin 68 mg/m² by concurrent 2-h intravenous infusion, 5-FU 1920 mg/m² 46-h intravenous infusion every 2 weeks (qd15).

mFOLFOX7

Salah-Eddin Al-Batran, Prof. Dr.

This is a controlled, open-label, randomized phase- II trial (1:1 randomization) investigating 5-FU + aflibercept and 5-FU + oxaliplatin in elderly and frail elderly patients with mCRC scheduled to receive first line treatment.

The current trial seeks to evaluate a new treatment option for elderly / frail elderly patients with mCRC including 5-FU - better tolerated than capecitabine in the FOCUS2 study - in conjunction with aflibercept, a broad active anti-angiogenic drug within a randomized phase-II setting. Patients will be randomized using a 1:1 randomization between 5-FU / aflibercept and 5-FU / oxaliplatin using the oxaliplatin-based regimen established in FOCUS2 trial. Main goal is to estimate the 6-months PFS rate with 5-FU / Aflibercept and the safety of this regimen. The decision to use a randomized phase-II design using the "FOCUS2- FOLFOX" is based on two assumptions; (i) Bias can be better controlled by using a randomized phase-II design (ii) A clear standard regimen in frail elderly cannot be defined, but FOLFOX was superior to 5-FU alone in FOCUS2 and the patient population included in the FOCUS2 study represents the patient population scheduled to be included in the current trial.

Provided the randomized phase-II study shows adequate efficacy of 5-FU / aflibercept and a tolerable safety profile, the study will be carried on to the phase-III part of the trial. Description of the terms and conditions to expand the current trial are not part of this protocol. Briefly, a potential phase-III study should aim at showing non-inferiority of 5-FU / aflibercept regarding 6-months PFS rate as primary endpoint. This would allow to include all patients from the phase-II part in the phase-III study in order to save time and patients.

Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer

Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Metastatic Colorectal Cancer

As calculated over the whole treatment duration and summarized descriptively by summary statistics.

AE's will be summarized by presenting the number and percentages of patients having any AE

Dose modifications, including discontinuations, will be summarized by presenting the number and percentages of patients having any dose modification

Rate of treatment discontinuations during the study

Summary of lab abnormalities as assessed in the documentation

Quality of life (QoL) as measured by EQ-5D-5L at d1 of each cycle and on EOT.

Geriatric assessment as measured by using G8, ADL and IADL

Overall treatment utility is evaluated according to the principles used in the FOCUS2 trial. Cf. Seymour et al. Geriatric oncol 2013.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer	NCT03530267	Colorectal Canc...	Aflibercept + m... mFOLFOX7	70 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer	NCT03530267	Colorectal Canc...	Aflibercept + m... mFOLFOX7	70 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer	NCT03530267	Colorectal Canc...	Aflibercept + m... mFOLFOX7	70 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Spots Global Cancer Trial Database for aflibercept + mlv5fu2