Clinical trial NCT00681876: Phase II Study of Avastin + Erbitux + Irinotecan as 2nd Line Treatment of Colorectal Cancer
Official title: Phase II Study of Avastin Plus Erbitux Plus Irinotecan as 2nd Line Treatment of Locally Advanced or Metastatic Colorectal Cancer in Patients Achieving Disease Progression as Best Response After 1st Line Treatment With FOLFIRI+Avastin or XELIRI+Avastin
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Metastatic colorectal cancer
Second line
Irinotecan
Erbitux (Cetuximab)
Avastin (Bevacizumab)
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2008-05-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II study will evaluate the efficacy of the combination of two monoclonal antibodies (Avastin + Erbitux) with irinotecan, in patients with colorectal cancer progressed after 1st line treatment with FOLFIRI Avastin or XELIRI Avastin.

Detailed description: Treating patients with primary resistance to the most active multi-agent combination remains a challenging clinical problem. The reported data demonstrated that addition of ERBITUX may reverse IRINOTECAN resistance. Further data support the feasibility of the combination of two monoclonal antibodies (AVASTIN+ERBITUX) with IRINOTECAN with better responses compared to historical controls (ERBITUX±IRINOTECAN). As such, a phase II study was designed to evaluate the efficacy of the combination of AVASTIN plus ERBITUX plus IRINOTECAN as second line treatment in patients progressing while on treatment with FOLFIRI AVASTIN or XELIRI AVASTIN

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed locally advanced or metastatic colorectal cancer.
* Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
* ECOG performance status ≤ 2
* Age 18 - 72 years
* Patients with de novo refractory disease (progression of disease as best response at 1st line therapy with FOLFOX/Avastin)
* Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL),renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function
* Patients must be able to understand the nature of this study
* Written informed consent

Exclusion Criteria:

* History of serious cardiac disease (unstable angina, congestive heart failure, uncontrolled cardiac arrhythmias).
* History of myocardial infarction or stroke within 6 months.
* Clinically significant peripheral vascular disease.
* History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0.
* Presence of central nervous system or brain mets.
* Evidence of bleeding diathesis or coagulopathy.
* Patients with known hypersensitive reaction to cetuximab
* Blood pressure \> 150/100 mmHg.
* Pregnant or lactating woman.
* Life expectancy \< 3 months.
* Previous radiotherapy within the last 4 weeks or \> 25% of bone marrow.
* Metastatic infiltration of the liver \>50%.
* Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy.
* Active infection requiring antibiotics on Day 1.
* Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer.
* Psychiatric illness or social situation that would preclude study compliance.

Primary outcomes:
measure: Time To Progression
timeFrame: 1 year
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
measure: Toxicity profile
timeFrame: Toxicity assessment on each chemotherapy cycle
measure: Quality of life, Symptoms improvement
timeFrame: Assessment every two cycles
Other outcomes:
Locations:
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis, Dep of Medical Oncology
city: Athens
country: Greece
facility: 401 Military Hospital of Athens
city: Athens
country: Greece
facility: : "Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
city: Athens
country: Greece
facility: Air Forces Military Hospital of Athens
city: Athens
country: Greece
facility: IASO" General Hospital of Athens, 1st Dep of Medical Oncology
city: Larissa
country: Greece
facility: State General Hospital of Larissa
city: Piraeus
country: Greece
facility: "Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: "Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
Study officials:
affiliation: University Hospital of Crete
name: John Souglakos, MD
role: PRINCIPAL_INVESTIGATOR
References: