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

NCT03530267 | Completed Phase 2 DMC

• 1 other identifier: ELDERLY
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 25

Brief 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.

Conditions

Colorectal Cancer

Keywords

colorectal cancer; 5-FU; Aflibercept; Oxaliplatin

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Rate of patients free of progression

  6 months

Secondary Outcomes (11)

• Safety: Dose intensities of study medication

  6 months

• Safety: Adverse events (AE)

  7 months

• Safety: Dose modification of study drug due to adverse events

  6 months

• Safety: Rate of treatment discontinuation due to toxicitiy

  6 months

• Safety: Laboratory abnormalities

  6 months

Study Arms (2)

Arm A (mFOLFOX7)

ACTIVE COMPARATOR

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.

Drug: mFOLFOX7

Arm B (Aflibercept + mLV5FU2)

EXPERIMENTAL

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

Interventions

Aflibercept + mLV5FU2 DRUG

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).

Arm B (Aflibercept + mLV5FU2)

mFOLFOX7 DRUG

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).

Arm A (mFOLFOX7)

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• STABIL - Statistische und Biometrische Lösungen: collaborator
• Trium Analysis Online GmbH: collaborator
• Sanofi: collaborator

Study Sites (25)

Phase Drei

Aschaffenburg, 63739, Germany

Location

HELIOS Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Klinikum Bayreuth

Bayreuth, 95445, Germany

Location

MVZ Seestrasse

Berlin, 13347, Germany

Location

Klinikum Bremen Nord

Bremen, 28755, Germany

Location

Kliniken Essen-Mitte

Essen, 45136, Germany

Location

Agaplesion Markus Krankenhaus

Frankfurt, 60431, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt, 60488, Germany

Location

Klinikum Garmisch-Partenkirchen GmbH

Garmisch-Partenkirchen, 82467, Germany

Location

Nationales Centrum für Tumorerkrankungen (NCT)

Heidelberg, 69120, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

DRK-Kliniken Nordhessen gGmbH

Kassel, 34121, Germany

Location

Ortenau Klinikum Lahr

Lahr, 77933, Germany

Location

Onkologisches Zentrum

Lebach, 66822, Germany

Location

Klinikum Ludwigshafen

Ludwigshafen, 67063, Germany

Location

Klinikum Magdeburg gGmbH

Magdeburg, 39130, Germany

Location

Tagestherapiezentrum am ITM Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Kliniken Ostalb

Mutlangen, 73557, Germany

Location

Klinikum der Universität München-Großhadern

München, 81377, Germany

Location

Kliniken des Landkreises Neumarkt in der Oberpfalz

Neumarkt in der Oberpfalz, 92318, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Clinical Research Stolberg GmbH

Stolberg, 52222, Germany

Location

Klinikum Mutterhaus Trier

Trier, 54290, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Klinikum Wilhelmshaven

Wilhelmshaven, 26389, Germany

Location

Related Publications (1)

• 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.

  PMID: 21570111 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: May 21, 2018
• Study Start: September 28, 2018
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (25)