Efficacy of FOLFOX+Bevacizumab in Combination With Irinotecan in the Treatment of Metastatic Colorectal Cancer (CHARTA)

Martin-Luther-Universität Halle-Wittenberg

Status and phase: Completed; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Oxaliplatin, 5FU/LV, Bevacizumab; Drug: 5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01321957

AIO-0209

Details and patient eligibility

About

The primary objective of this study is to evaluate the efficacy of Irinotecan in combination with FOLFOX+Bevacizumab versus FOLFOX+Bevacizumab alone in the first-line treatment of patients with metastatic colorectal cancer.

Full description

5-Fluorouracil and oxaliplatin (FOLFOX-Regimen) in combination with bevacizumab is regarded as standard first-line treatment in metastatic colorectal cancer [Saltz et al., 2008]. Current studies established the role of the FOLFOXIRI regimen [Souglakos et al., 2006, Falcone et al., 2007]. A further intensification of the therapy seems feasible yielding response rates up to 84% and a disease control rate up to 100% [Falcone, 2008, Santomaggio, 2009, Masi, 2010]. This trial evaluates the activity of an intensified first-line therapy for metastatic colorectal cancer compared to standard treatment.

Enrollment: 250 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present)

2. Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)

3. ECOG Performance status ≤ 2 (ECOG 2, only if tumor related)

4. Patients, who are able to tolerate intensive first lien treatment as judged by the investigator

5. Life expectancy > 3 months

6. Age ≥ 18 years

7. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin

   • 9 g/dl or 5.59 mmol/l

8. Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.

9. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin ≤ 1.5 x ULN

10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN

11. Signed, written informed consent

Exclusion criteria

1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present)

2. Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)

3. ECOG Performance status ≤ 2 (ECOG 2, only if tumor related)

4. Patients, who are able to tolerate intensive first lien treatment as judged by the investigator

5. Life expectancy > 3 months

6. Age ≥ 18 years

7. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin

   • 9 g/dl or 5.59 mmol/l

8. Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.

9. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin ≤ 1.5 x ULN

10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN

11. Signed, written informed consent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

250 participants in 2 patient groups

FOLFOX+Bevacizumab

Active Comparator group

Description:

bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)

Treatment:

Drug: Oxaliplatin, 5FU/LV, Bevacizumab

FOLFOX+Bevacizumab+Irinotecan

Experimental group

Description:

bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) irinotecan at a dose of 165 mg/m2 iv over two hours (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)

Treatment:

Drug: 5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan