Curative Resectability of Not Optimally Resectable Liver and/or Lung Metastases From Colorectal Carcinoma (CRC) Under Intensified Chemotherapy

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01126866
• Date of registration: 12/05/2010
• Primary sponsor: National Center for Tumor Diseases, Heidelberg
• Public title: Curative Resectability of Not Optimally Resectable Liver and/or Lung Metastases From Colorectal Carcinoma (CRC) Under Intensified Chemotherapy APRIORI
• Scientific title: Phase II Study on Curative Resectability of Not Optimally Resectable Liver and/or Lung Metastases From Colorectal Carcinoma (CRC) Under Intensified Chemotherapy (FOLFOXIRI/ Bevacizumab)
• Date of first enrolment: June 2009
• Target sample size: 35
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01126866
• Study type: Interventional
• Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Germany

Contacts

• Name: Dirk Jaeger, Prof. Dr.
• Affiliation: NCT Heidelberg

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Age =18 years

2. Indication:

- Histologically confirmed advanced colorectal carcinoma of UICC Stages IV with
liver and/or lung only metastases,which are not optimally resectable

- Measurable disease according to RECIST criteria.

- In case of liver metastases: 70% liver replacement and/or > 6 segments tumor
involved, and/or involvement of all three hepatic veins, and/or involvement of
the right and left portal pedicle, and/ or involvement of the vena cava.

- In case of lung metastases: No tumor with direct infiltration of myocardium,
esophagus, spine or intrapericardial large vessels. Preoperative data indicate a
significant loss of pulmonary function after pulmonary metastasectomy with
severe impairment of quality of life.

3. ECOG performance status of < 2.

4. Life expectancy of > 3 months

5. Laboratory parameters:

- Proteinuria at baseline:

- Patients with proteinuria <2+ on dipstick urinalysis.

- Patients with 2+ proteinuria on dipstick urinalysis at baseline should
undergo a 24-h urine collection and must have proteinuria <= 1 g of
protein/24 h.

- The required laboratory values at baseline are as follows:

- Hematology:

- Absolute neutrophil count (ANC) > 1.5 x 109/L

- Platelet count > 100 x 109/L

- Hemoglobin > 9 g/dL (may be transfused to maintain or exceed this
level)

- International Normalized Ratio (INR) < 1.5; aPTT <1.5 x ULN

- Biochemistry:

- Total bilirubin < 1.5 x upper limit of normal (ULN)

- AST, ALT < 2.5 x ULN in patients without liver metastases; < 5 x ULN
in patients with liver metastases

- Serum creatinine <2.0 mg/dL or 177 ƒÝmol/L

6. Willingness to give written informed consent, written consent for data protection and
willingness to participate and to comply with the study.

Exclusion Criteria:

1. Past or current history of malignancies other than colorectal carcinoma. Patients
with curatively treated basal and squamous cell carcinoma of the skin and/or in-situ
carcinoma of the cervix are eligible.

2. Previous chemotherapy (except adjuvant chemotherapy).

3. Extrahepatic and/or extrapulmonary meta-stases except of the initially removed lymph
node metastases.

4. History or evidence upon physical examination of CNS disease unless adequately
treated (e.g., seizure not controlled with standard medical therapy or history of
stroke).

5. Major surgical procedures, open biopsy, or significant traumatic injury within 28
days prior to study treatment start (wound healing has to be completed), or
anticipation of the need for major surgical procedure during the course of the study.

6. Evidence of bleeding diathesis or coagulopathy

7. Serious, non-healing wound, ulcer, or bone fracture

8. Treatment with investigational agents or participation in clinical trials within 30
days before study entry.

9. Clinically significant (i.e. active) cardiovascular disease, e.g., uncontrolled
hyper-tension, cerebrovascular accidents (. 6 months prior to treatment start),
myocardial infarction (. 6 months prior to treatment start), unstable angina, New
York Heart Association (NYHA) grade . II, congestive heart failure, serious cardiac
arrhythmia requiring medication.

10. Current or recent serious polyneuropathy (grade . 1 according to NCI CTCAE v3.0
criteria; exception: absence of tendon reflexes)

11. Hematopoietic diseases.

12. Known intra-abdominal inflammatory pro-cess or serious gastrointestinal ulceration.

13. Known dihydropyrimidine dehydrogenase (DPD) deficiency.

14. Thromboembolic events or severe hemorrhage ("T 6 months before treatment start).

15. Known hypersensitivity to oxaliplatin, the background medication (bevacizumab, FA or
5-FU) or to their compounds, incl. Chinese hamster ovary (CHO) cell proteins or other
recombinant human or humanized antibodies.

16. Known Gilbert-Syndrome

17. Evidence of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational regimen or patient at high risk from
treatment complications

18. As the following medication(s) can have interactive effects and may interfere with
the patient's ability to meet the study requirements, they cannot be administered
during the clinical study:

- sorivudine or analog compounds.

- Current or recent (within 10 days of first dose of study treatment) treatment
with full-dose oral or parenteral anticoagulants or thrombolytic agents (e.g.,
marcumar therapy) for therapeutic purposes.

- Current or recent (within 10 days of first dose of study treatment) chronic use
of aspirin (> 325 mg/day) or clopidogrel (> 75 mg/day).

19. Women, lactating, pregnant or of child-bearing potential and fertile men not using a
highly effective contraceptive method1.

[Women of childbearing potential must have a negative pregnancy test (serum b-HCG)
within 7 days before the first dose of study drug].

20. Patients who are confined by order of either judicial or administrative authorities
(according to ¡± 40 Abs. 1 S. 3 AMG).

21. Patients who are incapable to understand the aim, importance and consequences of the
study and to give legal informed consent (according to ¡± 40 Abs. 4 and ¡± 41 Abs. 2
and Abs. 3 AMG).

22. Patients with a history of a psychological illness or condition such as to interfere
with the patient's ability to understand the requirements of the study.

23. Patients who possibly are dependent on the sponsor or investigator.

24. Patients who have participated in this study before.



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

Health Condition(s) or Problem(s) studied

Colorectal Carcinoma

Intervention(s)

Drug: intensified chemotherapy (FOLFOXIRI/Bevacizumab)

Primary Outcome(s)

surgically complete resectability; S-CR [Time Frame: 12 month after Surgery]

Secondary Outcome(s)

Evaluate the acute and perioperative toxicity of preoperative chemotherapy according to NCI CTCAE v3.0 and all peri-and post-surgical complications [Time Frame: 12 month after surgery]

Survival rate (OS) and progression free survival (PFS) [Time Frame: 12 months after surgery or end of treatment.]

Secondary ID(s)

NCT-2007-11-02-1003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Pfizer

Roche Pharma AG