Clinical trial NCT00921661: Study of Intravenous Aflibercept in Combination With FOLFIRI in Japanese Patients With Metastatic Colorectal Cancer
Official title: A Dose-escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Aflibercept in Combination With Intravenous Irinotecan/5-fluorouracil/Isovorin (FOLFIRI) Administered Every 2 Weeks in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Neoplasms
Neoplasm Metastasis
Keywords: oxaliplatin
5-FU
Folinic Acid
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2009-06-16
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective is to determine the dose of aflibercept to be further studied in combination with irinotecan/5-fluorouracil/isovorin (FOLFIRI) in Japanese patients with metastatic colorectal cancer.

Secondary objectives of this study are to assess the safety profile of aflibercept, to determine the pharmacokinetics of aflibercept, to make a preliminary assessment of antitumor effects.


Eligibility criteria: Inclusion Criteria:

* Patients with histologically or cytologically proven malignant tumor of the colon or rectum which is metastatic and inoperable.
* Patients must have received at least one prior line of treatment with any standard of care, who have failed the treatment, or who have not been eligible for standard of care for safety reasons.

Exclusion Criteria:

* Treatment with chemotherapy, hormone therapy, radiotherapy, surgery, blood products, or any investigational agent within 28 days.
* ECOG Performance Status\>1
* Anticipated need for a major surgical procedure or radiation therapy during the study.
* Uncontrolled malignant ascites.
* History of brain metastases, spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease on screening CT or MRI scan.
* Pregnant or breast-feeding women.
* Uncontrolled hypertension
* Patients who have previously been treated with aflibercept
* History of abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days.
* History of hypersensitivity to any recombinant proteins, irinotecan, fluoropyrimidine or isovorin.
* Known dihydropyrimidine dehydrogenase deficiency.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Dose-limiting toxicity (DLT) combination with FOLFIRI
timeFrame: During the first 2 cycles (4 weeks) of study treatment
Secondary outcomes:
measure: physical examination, laboratory safety tests, adverse events
timeFrame: up to 60 days after last treatment
measure: Pharmacokinetics
timeFrame: up to 90 days after last treatment
measure: Tumor burden, endogenous free VEGF
timeFrame: every 3 cycles
measure: Immunogenicity
timeFrame: up to 90 days after last treatment
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Yoshino T, Yamazaki K, Yamaguchi K, Doi T, Boku N, Machida N, Onozawa Y, Asayama M, Fujino T, Ohtsu A. A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancer. Invest New Drugs. 2013 Aug;31(4):910-7. doi: 10.1007/s10637-012-9895-6. Epub 2012 Nov 20.