Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms (POLAF)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
FOLFIRI+aflibercept
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring metastatic colorectal cancer, FOLFIRI, aflibercept, oxaliplatin, ACE polymorphisms
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion
- Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis.
- 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,
- History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure
- Bowel obstruction.
Sites / Locations
- Spanish Cooperative Group for the Treatment of Digestive Tumors
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
FOLFIRI+aflibercept
Arm Description
Outcomes
Primary Outcome Measures
FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms.
Secondary Outcome Measures
Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE
Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Number of participants with adverse events as assessed by CTCAE v4.0.
Full Information
NCT ID
NCT02970916
First Posted
November 16, 2016
Last Updated
April 10, 2019
Sponsor
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT02970916
Brief Title
Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms
Acronym
POLAF
Official Title
A Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
May 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Collaborators
Sanofi
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
metastatic colorectal cancer, FOLFIRI, aflibercept, oxaliplatin, ACE polymorphisms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFIRI+aflibercept
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FOLFIRI+aflibercept
Intervention Description
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)
Primary Outcome Measure Information:
Title
FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms.
Time Frame
30 months
Secondary Outcome Measure Information:
Title
Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE
Time Frame
30 months
Title
Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time Frame
30 months
Title
Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time Frame
30 months
Title
Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time Frame
30 months
Title
Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time Frame
30 months
Title
Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
Time Frame
30 months
Title
Number of participants with adverse events as assessed by CTCAE v4.0.
Time Frame
30 months
Other Pre-specified Outcome Measures:
Title
Plasma VEGF levels circulating and their correlation with tumour-efficacy parameters (ORR, PFS and OS)
Time Frame
30 months
Title
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)
Time Frame
30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion
Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis.
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,
History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure
Bowel obstruction.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrique Aranda, MD-PhD
Organizational Affiliation
Hospital Universitario Reina Sofía
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Auxiliadora Gómez, MD-PhD
Organizational Affiliation
Hospital Universitario Reina Sofía
Official's Role
Study Chair
Facility Information:
Facility Name
Spanish Cooperative Group for the Treatment of Digestive Tumors
City
Madrona
ZIP/Postal Code
28007
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms
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