Combined Anticancer Treatment of Advanced Colon Cancer

Colorectal Cancer Metastatic Clinical Trial

— COMBATAC  

Official title:

Multimodality Treatment Including Pre- and Postoperative Systemic Chemotherapy Plus Cetuximab, Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Peritoneal Carcinomatosis Arising From Wild Type K-ras Colon Cancer: A Prospective Multicenter Phase II Study.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01540344
• Other study ID #: 24/06/2009
• Secondary ID: 2009-014040-11
• Status: Terminated
• Phase: Phase 2
• Start date: October 2010
• Est. completion date: October 2017

Study information

• Verified date: August 2018
• Source: University of Regensburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The COMBATAC study evaluates the the effect as assessed by progression-free survival (PFS) of perioperative systemic chemotherapy including cetuximab and cytoreductive surgery (CRS) and bidirectional hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis arising from colorectal cancer.

Description:

More than 10% of patients with colorectal cancer (CRC) already show peritoneal carcinomatosis at the time of initial diagnosis and up to 25% of all patients develop peritoneal carcinomatosis during the natural course of their disease as a common sign of tumor progression or recurrence.

The existing data suggests that CRS and HIPEC as an integral part of a multidisciplinary treatment concept may improve long-term survival of selected patients with peritoneal carcinomatosis of colonic origin. Moreover, hyperthermic peritoneal perfusion with oxaliplatin in combination with synchronous application of 5-FU/leucovorin seems to improve the efficacy of HIPEC in comparison to a mitomycin C-based intraperitoneal treatment regimen and may lead to a better local tumor control. The improved systemic treatment strategy with neoadjuvant chemotherapy may lead to increased rates of complete macroscopic cytoreduction and together with the adjuvant treatment to better control of distant metastasis and tumor recurrence. However, there is no prospective study available evaluating the clinical and oncological outcome after standard-of-care chemotherapy including targeted anticancer therapy in combination with CRS and HIPEC. The published morbidity and mortality rates after CRS and HIPEC are comparable to other major gastrointestinal surgery and seem to be acceptable considering the expected improvement of oncological outcome.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: October 2017
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 71 Years

Eligibility

Inclusion Criteria:

• Synchronous or metachronous peritoneal carcinomatosis arising from histologically proven colorectal or appendiceal adenocarcinoma

• Complete macroscopic cytoreduction (CCR-0/1)

• Free treatment interval of at least 6 month after the last chemotherapy

• Age over 18 and below 71 years

• Good general health status (Karnofsky > 70%, ECOG 0-2)

• Absence of hematogenous metastasis (lung, bone, brain, > 3 peripheric resectable liver metastases)

• Absence of contraindication for systemic chemotherapy and/or extended surgery

• Life expectancy greater than 6 months

• Written informed consent

• Creatinine clearance > 50 ml/min, serum creatinine = 1.5 x ULN

• Serum bilirubin = 1.5 x ULN (upper limit of normal), ASAT and ALAT = 2.5 x ULN

• Platelet count > 100,000 /ml, haemoglobin > 9 g/dl, neutrophile granulocytes = 1,500 /ml, International Normalized Ration (INR) = 2

• Absence of peripheral neuropathy > grade 1 (CTCAE v4.0)

• No pregnancy or breast feeding. Adequate contraception in fertile patients.

Exclusion Criteria:

• Incomplete cytoreduction

• Hematogenous metastasis including irresectable liver metastasis

• Prior chemotherapy or therapy with EGFR receptor antibody for metastatic disease

• K-ras mutation

• Known allergy to murine or chimeric monoclonal antibodies

• Histology of signet ring carcinoma

• Other malignancy than disease under study / second cancer

• Impaired liver, renal or hematologic function as mentioned above (inclusion criteria)

• Heart failure NYHA = 2 or significant Coronary Artery Disease

• Alcohol and/or drug abuse

• Patients unable or unwilling to comply with the study protocol, treatment or follow-up

• Patients included in other clinical trials interfering with the present study

Related Conditions & MeSH terms

• Carcinoma
• Colonic Neoplasms
• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Peritoneal Carcinomatosis

Intervention

Procedure:
• CRS
complete macroscopic cytoreduction (CC-0/1)

Drug:
• HIPEC
bidirectional hyperthermic intraperitoneal chemotherapy (HIPEC) with 400 mg/sqm 5-FU + 20 mg/sqm folinic acid IV and 300 mg/sqm oxaliplatin IP

Locations

Country	Name	City	State
Germany	Charité Campus Mitte, Humboldt-University Berlin	Berlin
Germany	Medical Center of the Friedrich-Alexander-University Erlangen- Nürnberg	Erlangen
Germany	Cologne-Merheim Medical Center, University Witten/Herdecke	Koeln
Germany	St. John of God Hospital Regensburg	Regensburg
Germany	University Hospital Regensburg	Regensburg
Germany	University Hospital, University of Tuebingen	Tuebingen
Germany	University Hospital Wuerzburg, Julius-Maximilians University	Wuerzburg

Sponsors (2)

Lead Sponsor	Collaborator
University of Regensburg	Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Glockzin G, Rochon J, Arnold D, Lang SA, Klebl F, Zeman F, Koller M, Schlitt HJ, Piso P. A prospective multicenter phase II study evaluating multimodality treatment of patients with peritoneal carcinomatosis arising from appendiceal and colorectal cancer: the COMBATAC trial. BMC Cancer. 2013 Feb 7;13:67. doi: 10.1186/1471-2407-13-67. — View Citation

Glockzin G, Zeman F, Croner RS, Königsrainer A, Pelz J, Ströhlein MA, Rau B, Arnold D, Koller M, Schlitt HJ, Piso P. Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peri — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		24 months
Secondary	Overall survival (OS)		5 years
Secondary	Feasibility of the combined treatment concept	Assessment of tumor progression, AE and SAE during treatment phase leading to modification or end of treatment.	9 months
Secondary	Quality of life (QoL)	assessed by EORTC-QLQ-C30	2 years
Secondary	Pathohistological regression	assessed by Dworak grade of regression in histology after surgery	16 weeks