Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Met. Colorectal Cancer (ELDERLY)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03530267|
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : June 3, 2022
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Drug: Aflibercept + mLV5FU2 Drug: mFOLFOX7||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||196 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Aflibercept and 5-FU vs. FOLFOX as 1st Line Treatment for Elderly or Frail Elderly Patients With Metastatic Colorectal Cancer|
|Actual Study Start Date :||September 28, 2018|
|Estimated Primary Completion Date :||September 15, 2022|
|Estimated Study Completion Date :||September 15, 2022|
Active Comparator: Arm A (mFOLFOX7)
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 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).
Experimental: Arm B (Aflibercept + mLV5FU2)
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.
Drug: Aflibercept + mLV5FU2
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).
- Progression-free survival (PFS) [ Time Frame: 6 months ]Rate of patients free of progression
- Safety: Dose intensities of study medication [ Time Frame: 6 months ]As calculated over the whole treatment duration and summarized descriptively by summary statistics.
- Safety: Adverse events (AE) [ Time Frame: 7 months ]AE's will be summarized by presenting the number and percentages of patients having any AE
- Safety: Dose modification of study drug due to adverse events [ Time Frame: 6 months ]Dose modifications, including discontinuations, will be summarized by presenting the number and percentages of patients having any dose modification
- Safety: Rate of treatment discontinuation due to toxicitiy [ Time Frame: 6 months ]Rate of treatment discontinuations during the study
- Safety: Laboratory abnormalities [ Time Frame: 6 months ]Summary of lab abnormalities as assessed in the documentation
- Efficacy: Response rates [ Time Frame: 2 years ]As measured by RECIST criteria v. 1.1
- Efficacy: Overall survival (OS) [ Time Frame: 2 years ]OS according to Kaplan-Meier
- Efficacy: PFS [ Time Frame: 2 years ]PFS according to Kaplan-Meier
- Patient reported outcomes (PRO): Quality of life [ Time Frame: 6 months ]Quality of life (QoL) as measured by EQ-5D-5L at d1 of each cycle and on EOT.
- PRO: Geriatric assessment [ Time Frame: 6 months ]Geriatric assessment as measured by using G8, ADL and IADL
- PRO: Overall treatment utility [ Time Frame: 6 months ]Overall treatment utility is evaluated according to the principles used in the FOCUS2 trial. Cf. Seymour et al. Geriatric oncol 2013.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03530267
|Contact: Ralf-Dieter Hofheinz, Prof. Dr.||+49621383 ext firstname.lastname@example.org|
|Contact: Claudia Pauligk, Dr.||+49697601 ext email@example.com|
|Study Chair:||Salah-Eddin Al-Batran, Prof. Dr.||Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest|