Combined Anticancer Treatment of Advanced Colon Cancer

Phase 2

Terminated

Brief 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.

Detailed 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 & 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

Arm && Interventions

Group	Intervention	Description
Treatment Arm	CRS	1. FOLFOX/FOLFIRI + cetuximab (6 cycles) 2. CRS and HIPEC 3. FOLFOX/FOLFIRI + cetuximab (6 cycles)
Treatment Arm	HIPEC	1. FOLFOX/FOLFIRI + cetuximab (6 cycles) 2. CRS and HIPEC 3. FOLFOX/FOLFIRI + cetuximab (6 cycles)

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	24 months

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	5 years
Feasibility of the combined treatment concept	9 months	Assessment of tumor progression, AE and SAE during treatment phase leading to modification or end of treatment.
Quality of life (QoL)	2 years	assessed by EORTC-QLQ-C30
Pathohistological regression	16 weeks	assessed by Dworak grade of regression in histology after surgery

Locations (7): Charité Campus Mitte, Humboldt-University Berlin
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Berlin, Germany
Cologne-Merheim Medical Center, University Witten/Herdecke
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Koeln, Germany
Medical Center of the Friedrich-Alexander-University Erlangen- Nürnberg
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Erlangen, Germany
University Hospital Regensburg
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Regensburg, Germany
St. John of God Hospital Regensburg
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Regensburg, Germany
University Hospital, University of Tuebingen
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Tuebingen, Germany
University Hospital Wuerzburg, Julius-Maximilians University
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Wuerzburg, Germany