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

NCT01126866 | Terminated Phase 2 DMC

• 1 other identifier: NCT-2007-11-02-1003
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to primarily assess the efficacy of an intensified chemotherapy consisting of a combination of FOLFOXIRI + bevacizumab. The main focus will be laid on the rate of patients who achieve secondary complete (R0)-resectable metastases. The FOLFIRI + bevacizumab as well as the FOLFOXIRI regimens have been shown previously to be both effective in the treatment of advanced CRC with having manageable toxicities. Therefore, an intensified chemotherapy combining these two standard regimens might be a promising therapeutic approach improving the treatment of metastatic disease and outcome of CRC. Patients with advanced colorectal carcinoma of UICC stage IV, and liver and/or lung metasta¬ses only, which are not optimally resectable, will be enrolled in this single-arm phase II study. A minimum of 4 cycles (=8 weeks) of chemo¬therapy prior to surgery is mandatory for all patients. However, patients may withdraw from the study at any time upon their own request. Treatment with preoperative chemothera¬py will continue until 2-4 weeks prior to surgery with the last application of bevacizumab (only FOLFOXIRI) 4 weeks before surgery, at longest 16 cycles (= 32 weeks) for candidates not eli¬gible for surgery. Treatment will be discontinued prematurely at disease progression or unacceptable toxicity. As secondary endpoints the acute and perioperative toxi¬city of preoperative chemotherapy according to NCI CTCAE v 3.0 including all peri-and post-surgical complications as well as progression free survival and overall survival and quality of life will be assessed.

Conditions

Colorectal Carcinoma

Keywords

advanced colorectal carcinoma; CRC; UICC Stages IV; liver and/or lung only metastases

Outcome Measures

Primary Outcomes (1)

• surgically complete resectability; S-CR

  To evaluate the proportion of patients who achieve surgically complete resectability (S-CR) of metastases after preoperative chemotherapy.

  12 month after Surgery

Secondary Outcomes (2)

• Evaluate the acute and perioperative toxicity of preoperative chemotherapy according to NCI CTCAE v3.0 and all peri-and post-surgical complications

  12 month after surgery

• Survival rate (OS) and progression free survival (PFS)

  12 months after surgery or end of treatment.

Study Arms (1)

preoperative chemotherapy

EXPERIMENTAL

Drug: intensified chemotherapy (FOLFOXIRI/Bevacizumab)

Interventions

intensified chemotherapy (FOLFOXIRI/Bevacizumab) DRUG

intensified chemotherapy (FOLFOXIRI/Bevacizumab)

preoperative chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• 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.
• ECOG performance status of \< 2.
• Life expectancy of \> 3 months
• 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

You may not qualify if:

• 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.
• Previous chemotherapy (except adjuvant chemotherapy).
• Extrahepatic and/or extrapulmonary meta-stases except of the initially removed lymph node metastases.
• 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).
• 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.
• Evidence of bleeding diathesis or coagulopathy
• Serious, non-healing wound, ulcer, or bone fracture
• Treatment with investigational agents or participation in clinical trials within 30 days before study entry.
• 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.
• Current or recent serious polyneuropathy (grade . 1 according to NCI CTCAE v3.0 criteria; exception: absence of tendon reflexes)
• Hematopoietic diseases.
• Known intra-abdominal inflammatory pro-cess or serious gastrointestinal ulceration.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Thromboembolic events or severe hemorrhage ("T 6 months before treatment start).
• 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.

Sponsors & Collaborators

• National Center for Tumor Diseases, Heidelberg: lead
• Roche Pharma AG: collaborator
• Pfizer: collaborator

Study Sites (1)

NCT

Heidelberg, 691220, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dirk Jaeger, Prof. Dr.

  NCT Heidelberg

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 12, 2010
• First Posted: May 20, 2010
• Study Start: June 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: June 1, 2011
• Last Updated: July 15, 2011

Record last verified: 2011-05

Locations

DE (1)