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Colorectal CancerPhase 2ELDERLYNCT03530267

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

A Phase 2 study testing Aflibercept + mLV5FU2 and mFOLFOX7 in people with Colorectal Cancer, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 25 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 70 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Aflibercept + mLV5FU2 and mFOLFOX7
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
25 sitesGermany
Study dates
28 Sep 2018to 1 Feb 2024
Phase
Phase 2
Are there results?
None posted in the registry

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

  • To enter this trial the oncologist has to confirm, that the patient was in his or her opinion not a candidate for standard full-dose combination therapy. Moreover, the oncologist has to state the reason for entering the trial (Advanced age alone versus both age and frailty). As an operational definition for frailty the G8 screening tool will be used upon inclusion of the patient in a standardized manner. Briefly, G8 is an established screening tool that includes seven items from the Mini Nutritional Assessment (MNA) and an age-related item (<80, 80 to 85, or 85 years). The total score can range from 0 to 17. The result on the G8 is considered abnormal if the score is ≤14, indicating a geriatric risk profile.
  • Patients have to have histologically confirmed mCRC with unidimensionally measurable inoperable advanced or metastatic disease
  • ECOG performance status of 2 or better.
  • Life expectancy of 3 months or longer at enrolment
  • Patients >70 years with no upper age limit
  • Previous adjuvant chemotherapy is allowed if completed more than 6 months before randomisation
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  • Previous rectal (chemo)radiotherapy is allowed if completed more than 6 months before randomisation
  • Hematological status:
  • Neutrophils (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Hemoglobin ≥ 9 g/dL
  • Adequate renal function:
  • Serum creatinine level ≤ 1.5 x upper limit normal (ULN)
  • Adequate liver function:
  • Serum bilirubin ≤ 1.5 x upper limit normal (ULN)
  • Alkaline phosphatase ≤ 2.5 x ULN (unless liver metastases are present, then < 5 x ULN in that case)
  • AST and ALT < 3 x ULN (unless liver metastases are present then < 5 x ULN in that case)
  • Proteinuria < 2+ (dipstick urinalysis) or ≤ 1 g/24hour
  • Signed and dated informed consent, and willing and able to comply with protocol requirements
  • Regular follow-up feasible
  • Male patients with a partner of childbearing potential must agree to use effective contraception (Pearl Index < 1) during the course of the trial and at least 3 months after last administration of the study drug.

Who cannot join

  • Prior systemic chemotherapy for mCRC
  • Other concomitant or previous malignancy, except:
  • Adequately treated in-situ carcinoma of the uterine cervix
  • Basal or squamous cell carcinoma of the skin
  • Cancer in complete remission for > 5 years
  • Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 Days
Show all 28Show fewer
  • History or evidence upon physical examination of CNS metastasis unless adequately treated (irradiation and no seizure with appropriate treatment)
  • Uncontrolled hypercalcemia
  • Pre-existing peripheral neuropathy (NCI grade ≥2)
  • Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
  • Treatment with any other investigational medicinal product within 28 days prior to study entry.
  • Significant cardiovascular disease:
  • Cardiovascular accident or myocardial infarction or unstable angina ≤6 months before start of study treatment
  • Severe cardiac arrhythmia
  • New York Heart Association grade ≥2 congestive heart failure
  • Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
  • History of stroke or transient ischemic attack ≤6 months before start of study treatment
  • Coronary/peripheral artery bypass graft ≤6 months before start of study treatment.
  • Deep vein thrombosis or thromboembolic events ≤1 month before start of study treatment
  • Patients with known allergy to any excipient to study drugs,
  • Any of the following within 3 months prior to randomization: Grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
  • Bowel obstruction.
  • Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Involvement in the planning and/or conduct of the study (applies to both Sanofi staff and/or staff of sponsor and study site)
  • Patient who might be dependent on the sponsor, site or the investigator
  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

Germany25 sites

  • Phase Drei

    Aschaffenburg, 63739

  • HELIOS Klinikum Bad Saarow

    Bad Saarow, 15526

  • Klinikum Bayreuth

    Bayreuth, 95445

  • MVZ Seestrasse

    Berlin, 13347

  • Klinikum Bremen Nord

    Bremen, 28755

  • Kliniken Essen-Mitte

    Essen, 45136

  • Agaplesion Markus Krankenhaus

    Frankfurt, 60431

  • Krankenhaus Nordwest GmbH

    Frankfurt, 60488

  • Klinikum Garmisch-Partenkirchen GmbH

    Garmisch-Partenkirchen, 82467

  • Nationales Centrum für Tumorerkrankungen (NCT)

    Heidelberg, 69120

  • Städtisches Klinikum Karlsruhe

    Karlsruhe, 76133

  • DRK-Kliniken Nordhessen gGmbH

    Kassel, 34121

  • Ortenau Klinikum Lahr

    Lahr, 77933

  • Onkologisches Zentrum

    Lebach, 66822

  • Klinikum Ludwigshafen

    Ludwigshafen, 67063

  • Klinikum Magdeburg gGmbH

    Magdeburg, 39130

  • Tagestherapiezentrum am ITM Universitätsmedizin Mannheim

    Mannheim, 68167

  • Klinikum der Universität München-Großhadern

    München, 81377

  • Kliniken Ostalb

    Mutlangen, 73557

  • Kliniken des Landkreises Neumarkt in der Oberpfalz

    Neumarkt in der Oberpfalz, 92318

  • Studienzentrum Onkologie Ravensburg

    Ravensburg, 88212

  • Clinical Research Stolberg GmbH

    Stolberg, 52222

  • Klinikum Mutterhaus Trier

    Trier, 54290

  • Universitätsklinikum Tübingen

    Tübingen, 72076

  • Klinikum Wilhelmshaven

    Wilhelmshaven, 26389

Other trials in Germany

About this study

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

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.

Read the detailed description

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.

Being tested
Aflibercept + mLV5FU2, mFOLFOX7
Keywords
colorectal cancer, 5-FU, Aflibercept, Oxaliplatin
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Aflibercept + mLV5FU2Drug

    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).

  • mFOLFOX7Drug

    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).

Study groups in NCT03530267
Study groupRoleWhat they receive
Arm A (mFOLFOX7)Active comparatorPatients 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.
Receives: Drug: mFOLFOX7
Arm B (Aflibercept + mLV5FU2)ExperimentalPatients 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.
Receives: Drug: Aflibercept + mLV5FU2

What is being measured

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

  1. Progression-free survival (PFS)

    Rate of patients free of progression

    Measured: 6 months

Secondary outcomes (11)

  1. Safety: Dose intensities of study medication

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

    Measured: 6 months

  2. Safety: Adverse events (AE)

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

    Measured: 7 months

  3. Safety: Dose modification of study drug due to adverse events

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

    Measured: 6 months

  4. Safety: Rate of treatment discontinuation due to toxicitiy

    Rate of treatment discontinuations during the study

    Measured: 6 months

  5. Safety: Laboratory abnormalities

    Summary of lab abnormalities as assessed in the documentation

    Measured: 6 months

  6. Efficacy: Response rates

    As measured by RECIST criteria v. 1.1

    Measured: 2 years

  7. Efficacy: Overall survival (OS)

    OS according to Kaplan-Meier

    Measured: 2 years

  8. Efficacy: PFS

    PFS according to Kaplan-Meier

    Measured: 2 years

  9. Patient reported outcomes (PRO): Quality of life

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

    Measured: 6 months

  10. PRO: Geriatric assessment

    Geriatric assessment as measured by using G8, ADL and IADL

    Measured: 6 months

  11. PRO: Overall treatment utility

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

    Measured: 6 months

Timeline

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

  1. First posted21 May 2018
  2. Study start28 Sep 2018
  3. Primary completion1 Feb 2024
  4. Study completion1 Feb 2024

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03530267
Sponsor's protocol ID
ELDERLY
Acronym
ELDERLY
Status last verified
Feb 2024
First submitted
8 May 2018
Last updated
23 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Publications

  • Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, O'Mahony MS, Maughan TS, Parmar M, Langley RE; FOCUS2 Investigators; National Cancer Research Institute Colorectal Cancer Clinical Studies Group. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011 May 21;377(9779):1749-59. doi: 10.1016/S0140-6736(11)60399-1. Epub 2011 May 11.

    PubMed 21570111

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aflibercept + mLV5FU2 and mFOLFOX7 in people with Colorectal Cancer, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 25 sites in Germany.

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 21 inclusion and 28 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: finished, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: 6 months). 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 NCT03530267, 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 23 Feb 2024.

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