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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02970916
• Date of registration: 16/11/2016
• Prospective Registration: No
• Primary sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Public title: Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms POLAF
• Scientific title: A Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms
• Date of first enrolment: November 2016
• Target sample size: 100
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02970916
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Spain

Contacts

• Name: Auxiliadora Gómez, MD-PhD
• Affiliation: Hospital Universitario Reina Sofía

• Name: Enrique Aranda, MD-PhD
• Affiliation: Hospital Universitario Reina Sofía

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed and dated informed consent, and willing and able to comply with protocol
requirements,

2. Histologically proven adenocarcinoma of the colon and/or rectum,

3. Metastatic disease confirmed.

4. Existence of at least one measurable unidimensional lesion using CT or MRI based on
the RECIST criteria, version 1.1

5. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has
progressed after an oxaliplatin-containing regimen.

6. Age =18 years

7. World Health Organization (WHO) Performance status (PS) 0-2,

8. Hematological status: neutrophils (ANC) =1.5x109 /L; platelets =100x109 /L;
haemoglobin =9g/dL

9. Adequate renal function: serum creatinine level < 1.5 x ULN

10. Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline
phosphatase (ALP) <5xULN

11. Proteinuria <2+ (dipstick urinalysis) or =1g/24hour.

12. Regular follow-up feasible.

13. For female patients of childbearing potential, negative serum pregnancy test

14. 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:

1. Uncontrolled hypercalcemia,

2. Pre-existing permanent neuropathy (NCI grade >2)

3. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or
diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or
hypertensive ncephalopathy,

4. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular
targeted therapy, immunotherapy),

5. Treatment with any other investigational medicinal product within 28 days prior to
study entry.

6. Other serious and uncontrolled non-malignant disease,

7. 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),

8. Known Gilbert's syndrome

9. Intolerance to atropine sulfate or loperamide

10. Known dihydropyrimidine dehydrogenase deficiency

11. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion

12. 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.

13. 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,

14. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic
injury within the last 28 days

15. Pregnant or breastfeeding women,

16. Patients with known allergy to any excipient to study drugs,

17. History of myocardial infarction and/or stroke within 6 months prior to inclusion,
NYHA class III and IV congestive heart failure

18. Bowel obstruction.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Colorectal Cancer

Intervention(s)

Drug: FOLFIRI+aflibercept

Primary Outcome(s)

FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms. [Time Frame: 30 months]

Secondary Outcome(s)

Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE [Time Frame: 30 months]

Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE [Time Frame: 30 months]

Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE [Time Frame: 30 months]

Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE [Time Frame: 30 months]

Number of participants with adverse events as assessed by CTCAE v4.0. [Time Frame: 30 months]

Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE [Time Frame: 30 months]

Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE [Time Frame: 30 months]

Secondary ID(s)

TTD-16-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Sanofi