Phase II Study of Avastin + Erbitux + Irinotecan as 2nd Line Treatment of Colorectal Cancer

Sponsor

Hellenic Oncology Research Group (Other)

Overall Status

Terminated

CT.gov ID

NCT00681876

Collaborator

University Hospital of Crete (Other)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Irinotecan Drug: Avastin Drug: Erbitux	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Irinotecan+Avastin+Erbitux	Drug: Irinotecan Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression Other Names: CPT-11 Campto Drug: Avastin Avastin (IV) 10 mgr/Kgr on day 1 every 2 weeks until progression Other Names: Bevacizumab Drug: Erbitux Erbitux (IV)500 mg/m2 on day 1 every two weeks until progression Other Names: Cetuximab

Arm

Intervention/Treatment

Experimental: 1

Irinotecan+Avastin+Erbitux

Drug: Irinotecan

Irinotecan (IV) 150 mg/m2 on day 1 every two weeks until progression

Other Names:

CPT-11

Campto

Drug: Avastin

Avastin (IV) 10 mgr/Kgr on day 1 every 2 weeks until progression

Other Names:

Bevacizumab

Drug: Erbitux

Erbitux (IV)500 mg/m2 on day 1 every two weeks until progression

Other Names:

Cetuximab

Outcome Measures

Primary Outcome Measures

Time To Progression [1 year]

Secondary Outcome Measures

Objective Response Rate [Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)]
Toxicity profile [Toxicity assessment on each chemotherapy cycle]
Quality of life, Symptoms improvement [Assessment every two cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 72 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	University General Hospital of Alexandroupolis, Dep of Medical Oncology	Alexandroupolis	Greece
2	401 Military Hospital of Athens	Athens	Greece
3	: "Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Athens	Greece
4	Air Forces Military Hospital of Athens	Athens	Greece
5	IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Athens	Greece
6	State General Hospital of Larissa	Larissa	Greece
7	"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology	Piraeus	Greece
8	"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology	Thessaloniki	Greece