Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms

NCT02970916 | Completed Phase 2

• 1 other identifier: TTD-16-02
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess FOLFIRI+aflibercept efficacy in patients with or without ACE polymorphisms in terms of Progression-free survival (PFS).

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; FOLFIRI; aflibercept; oxaliplatin; ACE polymorphisms

Outcome Measures

Primary Outcomes (1)

• FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms.

  30 months

Secondary Outcomes (7)

• Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE

  30 months

• Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE

  30 months

• Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE

  30 months

• Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE

  30 months

• Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE

  30 months

Other Outcomes (2)

• Plasma VEGF levels circulating and their correlation with tumour-efficacy parameters (ORR, PFS and OS)

  30 months

• Other biomarkers in serum and tumour tissue associated with cell and tumour growth and/or involved in the mechanism of action of FOLFIRI+aflibercept and their correlation with tumour-efficacy parameters (ORR, PFS and OS)

  30 months

Study Arms (1)

FOLFIRI+aflibercept

EXPERIMENTAL

Drug: FOLFIRI+aflibercept

Interventions

FOLFIRI+aflibercept DRUG

Aflibercept: 4 mg/kg administered intravenous infusion on day 1 FOLFIRI regimen immediately after aflibercept: Irinotecan:180 mg/m2 intravenous infusion, folinic acid (dl racemic): 400 mg/m2 intravenous infusion, followed by 5-fluorouracil (5-FU): 400 mg/m2 intravenous bolus, followed by 5-FU: 2400 mg/m2 continuous intravenous infusion over 46 hours. \* folinic acid: 400 mg/m² (racémic) or 200 mg/m² (L-form)

FOLFIRI+aflibercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent, and willing and able to comply with protocol requirements,
• Histologically proven adenocarcinoma of the colon and/or rectum,
• Metastatic disease confirmed.
• Existence of at least one measurable unidimensional lesion using CT or MRI based on the RECIST criteria, version 1.1
• Patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed after an oxaliplatin-containing regimen.
• Age ≥18 years
• World Health Organization (WHO) Performance status (PS) 0-2,
• Hematological status: neutrophils (ANC) ≥1.5x109 /L; platelets ≥100x109 /L; haemoglobin ≥9g/dL
• Adequate renal function: serum creatinine level \< 1.5 x ULN
• Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase (ALP) \<5xULN
• Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour.
• Regular follow-up feasible.
• For female patients of childbearing potential, negative serum pregnancy test
• Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.

You may not qualify if:

• Uncontrolled hypercalcemia,
• Pre-existing permanent neuropathy (NCI grade \>2)
• Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive ncephalopathy,
• 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.
• Other serious and uncontrolled non-malignant disease,
• History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
• Known Gilbert's syndrome
• Intolerance to atropine sulfate or loperamide
• Known dihydropyrimidine dehydrogenase deficiency
• Other concomitant or previous malignancy, except: i/ adequately treated insitu carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ 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
• Pregnant or breastfeeding women,
• Patients with known allergy to any excipient to study drugs,
• Bowel obstruction.

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Sanofi: collaborator

Study Sites (1)

Spanish Cooperative Group for the Treatment of Digestive Tumors

Madrona, 28007, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

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

• Enrique Aranda, MD-PhD

  Hospital Universitario Reina Sofía

  STUDY CHAIR

• Auxiliadora Gómez, MD-PhD

  Hospital Universitario Reina Sofía

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: November 22, 2016
• Study Start: November 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: December 1, 2018
• Last Updated: April 11, 2019

Record last verified: 2019-04

Locations

ES (1)