Clinical trial NCT02497157: Bevacizumab + Triplet Treatment for Untreated With Chemotherapy Metastatic Colorectal Cancer
Official title: Phase II Trial of FOLFOXIRI + Bevacizumab in Patients With Untreated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: bevacizumab
oxaliplatin
irinotecan
hydrochloride hydrate
fluorouracil
levofolinate calcium
Lead sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Sponsor class: OTHER
Collaborators: name: Hiroshima Prefectural Hospital
name: National Hospital Organization Shikoku Cancer Center
First posted: 2015-07-14
Enrollment: 45
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of fluorouracil (5-FU), levofolinate calcium (l-LV), oxaliplatin (L-OHP) and irinotecan hydrochloride hydrate (CPT-11) (FOLFOXIRI) plus bevacizumab in untreated metastatic colorectal cancer patients who harbor Uridine diphosphate (UDP)-glucuronosyl transferase 1A1 (UGT1A1) \*1/\*1, \*1/\*6 or \*1/\*28.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the colon or rectum.
2. Unresectable or recurrent colorectal cancer patient.
3. One or more measurable lesion in RECIST ver.1.1 criteria.
4. No prior chemotherapy, immunotherapy, and radiotherapy.
5. Life expectancy at least 3 months.
6. Patients who harbor UGT1A1\*1/\*1, \*1/\*6 or \*1/\*28.
7. The Eastern Cooperative Oncology Group (ECOG) performance status of =\<1.
8. Vital organ functions (listed below) are preserved within 14 days prior to entry.

   White blood cell count (WBC): \>= 3,000 per cubic millimeter Neu: \>= 1,500 per cubic millimeter Platelet count (PLT): \>= 100,000 per cubic millimeter Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT): \<= 100 IU/L, \<= 150 IU/L in cases with liver metastasis T-bil: \<= 1.5 mg/dL Serum creatinine: \<= 1.50 mg/dL Proteinuria: \<= 1+ Prothrombin time-international normalized ratio (PT-INR): \< 1.5
9. Written informed consent.

Exclusion Criteria:

1. Vermiform appendix cancer and anal canal cancer.
2. Administration of blood products/ granulocyte-colony stimulating factor (G-CSF), and blood transfusion within 14 days prior to enrollment.
3. Synchronous multiple malignancy or metachronous multiple malignancy less than 5 years disease free interval.
4. Hepatitis B virus antigen (HBs-Ag)(+), or hepatitis C virus antibody (HCV-Ab)(+).
5. History of severe allergy.
6. Sensory alteration or paresthesia interfering with function.
7. Prior radiotherapy for ilium and abdomen.
8. Infectious disease.
9. Uncontrolled diarrhea.
10. Ileus or bowel obstruction.
11. Interstitial lung disease or pulmonary fibrosis.
12. Malignant coelomic fluid required drainage.
13. Administration of atazanavir sulfate.
14. Heart disease to be clinically problem.
15. Major surgical procedure or intestinal resection within 28 days prior to enrollment or colostomy within 14 days prior to enrollment.
16. Known brain metastasis or strongly suspected of brain metastasis.
17. History of a thromboembolic disease.
18. Receiving anti-platelet drugs.
19. Poorly controlled gastrointestinal ulcer.
20. History of intestinal perforation within the past 12 months.
21. Poorly controlled hypertension.
22. Poorly controlled diabetes mellitus.
23. Severe mental disorders.
24. Women who are pregnant or nursing, men and women who wish to conceive a child or with no intention to contraception.
25. Any other cases who are regarded as inadequate for study enrollment by investigators.

Primary outcomes:
measure: Response rate (RR) by response evaluation criteria in solid tumors (RECIST v1.1)
timeFrame: Up to 18 months
Secondary outcomes:
measure: Time to treatment failure (TTF)
timeFrame: Up to 18 months
measure: Progression-free survival (PFS)
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: R0 resection rate
timeFrame: Up to 18 months
measure: Relative dose intensity (RDI)
timeFrame: Up to 18 months
measure: Incidence of adverse events
timeFrame: Up to 3 years
Other outcomes:
measure: Early tumor shrinkage (ETS) rates in 8 weeks after starting the treatment, evaluated by RECIST v1.1
timeFrame: Baseline (week 0), week 8
measure: Deepness of response (DoR)
timeFrame: Up to 3 years
Locations:
city: Matsuyama-city
country: Japan
facility: Matsuyama Red Cross Hospital
state: Ehime-prefecture
city: Kita-gun, Miki-cho
country: Japan
facility: Kagawa University Hospital
state: Kagawa-prefecture
city: Kurashiki-city
country: Japan
facility: Kawasaki Medical School Hospital
state: Okayama-prefecture
city: Okayama-city
country: Japan
facility: Okayama Saiseikai General Hospital
state: Okayama-prefecture
city: Okayama-city
country: Japan
facility: Okayama University Hospital
state: Okayama-prefecture
city: Okayama-city
country: Japan
facility: Okayama Rosai Hospital
state: Okayama-prefecture
city: Komatsushima-city
country: Japan
facility: Tokushima Red Cross Hospital
state: Tokushima-prefecture
Study officials:
affiliation: Hiroshima Prefectural Hospital
name: Katsunori Shinozaki, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Hospital Organization Shikoku Cancer Center
name: Tomohiro Nishina, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: