Clinical trial NCT01540344: Combined Anticancer Treatment of Advanced Colon Cancer
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Peritoneal Carcinomatosis
Colorectal Cancer Metastatic
Keywords: peritoneal carcinomatosis
cytoreductive surgery
HIPEC
colorectal cancer
Lead sponsor: University of Regensburg
Sponsor class: OTHER
Collaborators: name: Heinrich-Heine University, Duesseldorf
First posted: 2012-02-28
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 71
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years
measure: Feasibility of the combined treatment concept
timeFrame: 9 months
measure: Quality of life (QoL)
timeFrame: 2 years
measure: Pathohistological regression
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Mitte, Humboldt-University Berlin
city: Erlangen
country: Germany
facility: Medical Center of the Friedrich-Alexander-University Erlangen- Nürnberg
city: Koeln
country: Germany
facility: Cologne-Merheim Medical Center, University Witten/Herdecke
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Regensburg
country: Germany
facility: St. John of God Hospital Regensburg
city: Tuebingen
country: Germany
facility: University Hospital, University of Tuebingen
city: Wuerzburg
country: Germany
facility: University Hospital Wuerzburg, Julius-Maximilians University
Study officials:
affiliation: University of Regensburg
name: Pompiliu Piso, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Glockzin G, Zeman F, Croner RS, Konigsrainer A, Pelz J, Strohlein MA, Rau B, Arnold D, Koller M, Schlitt HJ, Piso P. Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial. Clin Colorectal Cancer. 2018 Dec;17(4):285-296. doi: 10.1016/j.clcc.2018.07.011. Epub 2018 Jul 31.