Colorectal Cancer Metastatic, Peritoneal Carcinomatosis
Conditions
Keywords
peritoneal carcinomatosis, cytoreductive surgery, HIPEC, colorectal cancer
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.
Interventions
PROCEDURECRS
complete macroscopic cytoreduction (CC-0/1)
DRUGHIPEC
bidirectional hyperthermic intraperitoneal chemotherapy (HIPEC) with 400 mg/sqm 5-FU + 20 mg/sqm folinic acid IV and 300 mg/sqm oxaliplatin IP
Sponsors
Heinrich-Heine University, Duesseldorf
University of Regensburg
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) | 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Germany
Outcome results
None listed