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

Metastatic Colorectal Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02970916
• Other study ID #: TTD-16-02
• Status: Completed
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: December 2018

Study information

• Verified date: April 2019
• Source: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• FOLFIRI+aflibercept
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)

Locations

Country	Name	City	State
Spain	Spanish Cooperative Group for the Treatment of Digestive Tumors	Madrona

Sponsors (2)

Lead Sponsor	Collaborator
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)	Sanofi

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma VEGF levels circulating and their correlation with tumour-efficacy parameters (ORR, PFS and OS)		30 months
Other	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
Primary	FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms.		30 months
Secondary	Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE		30 months
Secondary	Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE		30 months
Secondary	Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE		30 months
Secondary	Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE		30 months
Secondary	Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE		30 months
Secondary	Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE		30 months
Secondary	Number of participants with adverse events as assessed by CTCAE v4.0.		30 months