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

• ClinicalTrials.gov Identifier: NCT01321957
• Recruitment Status: Completed
• First Posted: March 24, 2011
• Last Update Posted: October 25, 2018
• Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Collaborator: Roche Pharma AG
• Information provided by (Responsible Party): Hans-Joachim Schmoll, MD, Martin-Luther-Universität Halle-Wittenberg

Tracking Information

• First Submitted Date: March 23, 2011
• First Posted Date: March 24, 2011
• Last Update Posted Date: October 25, 2018
• Actual Study Start Date: May 2011
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 25, 2013): progression free survival rate [ Time Frame: 9 months after first study drug administration ]
• Original Primary Outcome Measures (submitted: March 23, 2011): progression free survival rate [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: October 23, 2018)

• tumour response according to RECIST v 1.1 [ Time Frame: until progression of disease for a maximum of two years after end of treatment ]
• Secondary resection rate [ Time Frame: for a maximum of two years after end of treatment ]
• Progression free survival rate [ Time Frame: until progression of disease for a maximum of two years after end of treatment ]
• Overall survival [ Time Frame: until death for a maximum of two years after end of treatment ]
• Adverse events [ Time Frame: 18 months after the date of last study drug administration ]
  Toxicity of study medication
• Quality of Life evaluated by questionnaire [ Time Frame: Until end of treatment (maximum 2 years after first study drug administration) ]
  Quality of Life evaluated using questionnaire EORTC QLQ-30

Original Secondary Outcome Measures (submitted: March 23, 2011)

• safety assessments will include physical examinations, vital signs, clinical laboratory profile and monitoring of adverse events [ Time Frame: whole study, every two weeks ]
• tumour response according to RECIST v 1.1 [ Time Frame: every two monthsfor the first 6 months and afterwards every 3months. ]
• Quality of life [ Time Frame: during treatment period every 8/12 weeks and at the end of treatment ]
  QoL will be assessed using the EORTC QLQ-C30 and the module CR29 at baseline,
• Incidence and survival (PFS and OS) [ Time Frame: Retrospective analysis ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of FOLFOX+Bevacizumab in Combination With Irinotecan in the Treatment of Metastatic Colorectal Cancer
• Official Title: FOLFOX and Bevacizumab With or Without Irinotecan in First-line Treatment for Metastatic Colorectal Cancer. A Randomized Phase II Study
• Brief Summary: 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

• Drug: Oxaliplatin, 5FU/LV, Bevacizumab
  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)
  Other Names:

  • Bevacizumab
  • Oxaliplatin
  • I-LV
  • 5-FU
• Drug: 5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan
  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)
  Other Names:

  • Bevacizumab
  • Oxaliplatin
  • I-LV
  • 5-FU
  • Irinotecan

Study Arms

• Active Comparator: FOLFOX+Bevacizumab
  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)
  Intervention: Drug: Oxaliplatin, 5FU/LV, Bevacizumab
• Experimental: FOLFOX+Bevacizumab+Irinotecan
  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)
  Intervention: Drug: 5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan

Publications *

• Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
• Stein A, Glockzin G, Wienke A, Arnold D, Edelmann T, Hildebrandt B, Hollerbach S, Illerhaus G, Konigsrainer A, Richter M, Schlitt HJ, Schmoll HJ. Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature. BMC Cancer. 2012 Aug 16;12:356. doi: 10.1186/1471-2407-12-356.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 23, 2011): 250
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 15, 2018
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01321957
• Other Study ID Numbers: AIO-0209
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hans-Joachim Schmoll, MD, Martin-Luther-Universität Halle-Wittenberg
• Original Responsible Party: Prof. Dr. med. Hans-Joachim Schmoll, Martin-Luther-Universität Halle-Wittenberg
• Current Study Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Original Study Sponsor: Same as current
• Collaborators: Roche Pharma AG

Investigators

• Principal Investigator: Hans-Joachim Schmoll, MD; Universitätsklinikum Halle

• PRS Account: Martin-Luther-Universität Halle-Wittenberg
• Verification Date: October 2018