Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

Conditions

Colorectal Cancer, Primary Peritoneal Cavity Cancer

Keywords

recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, peritoneal carcinomatosis

Brief summary

RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether systemic chemotherapy is more effective with or without intraperitoneal chemohyperthermia in treating patients with peritoneal carcinomatosis from colorectal cancer. PURPOSE: This randomized phase III trial is studying systemic chemotherapy to see how well it works compared with or without intraperitoneal chemohyperthermia in treating patients undergoing surgery for peritoneal carcinomatosis from colorectal cancer.

Detailed description

OBJECTIVES: Primary * Compare overall survival of patients with peritoneal carcinoma of colorectal origin undergoing complete surgical resection and receiving systemic chemotherapy with versus without intraperitoneal chemohyperthermia. Secondary * Evaluate recurrence-free survival of these patients. * Evaluate treatment toxicities. * Determine morbidity from surgical complications. * Determine prognostic factors of survival. OUTLINE: This is a multicenter study. Patients are stratified according to participating center, residual tumor status (R0/R1 vs R2 ≤ 1 mm), prior regimens of systemic chemotherapy (first vs ≥ second), and preoperative systemic chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms. All patients undergo maximal surgical resection of the tumor. * Arm I: Patients receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and/or after surgery). Patients must stop systemic chemotherapy at least 1 month before receiving intraperitoneal chemohyperthermia (CHIP). If bevacizumab is given as neoadjuvant therapy, then systemic chemotherapy must be discontinued 6 weeks before beginning CHIP. Patients undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes. * Arm II: Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery). Tumor markers (ACE and CA 19-9) are assessed at baseline, at 1 month after surgery, and then at follow-up visits. After completion of study therapy, patients are followed at 1 and 3 months, every 3 months for 3 years, and then every 6 months for 2 years.

Quénet F, Elias D, Roca L, Goéré D, Ghouti L, Pocard M, Facy O, Arvieux C, Lorimier G, Pezet D, Marchal F, Loi V, Meeus P, Juzyna B, de Forges H, Paineau J, Glehen O, UNICANCER-GI Group and BIG Renape Group.

2021-01-18514 citations

10.1016/s1470-2045(20)30599-4

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6)

Rovers KP, Bakkers C, Simkens GAAM, Burger JWA, Nienhuijs SW, Creemers GM, Thijs AMJ, Brandt-Kerkhof ARM, Madsen EVE, Ayez N, de Boer NL, van Meerten E, Tuynman JB, Kusters M, Sluiter NR, Verheul HMW, van der Vliet HJ, Wiezer MJ, Boerma D, Wassenaar ECE, Los M, Hunting CB, Aalbers AGJ, Kok NFM, Kuhlmann KFD, Boot H, Chalabi M, Kruijff S, Been LB, van Ginkel RJ, de Groot DJA, Fehrmann RSN, de Wilt JHW, Bremers AJA, de Reuver PR, Radema SA, Herbschleb KH, van Grevenstein WMU, Witkamp AJ, Koopman M, Haj Mohammad N, van Duyn EB, Mastboom WJB, Mekenkamp LJM, Nederend J, Lahaye MJ, Snaebjornsson P, Verhoef C, van Laarhoven HWM, Zwinderman AH, Bouma JM, Kranenburg O, van 't Erve I, Fijneman RJA, Dijkgraaf MGW, Hemmer PHJ, Punt CJA, Tanis PJ, de Hingh IHJT, Dutch Peritoneal Oncology Group (DPOG), Dutch Colorectal Cancer Group (DCCG).

2019-04-2581 citations

10.1186/s12885-019-5545-0

Heated Chemo Showed No Benefit With Cytoreductive Surgery in Colon Cancer

Christina Bennett

Oncology Times2018-07-25

10.1097/01.cot.0000544350.38861.28

A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7.

François Quénet, Dominique Élias, Lise Roca, Diane Goèré, Laurent Ghouti et al. (18 authors)

Journal of Clinical Oncology2018-06-07325 citations

10.1200/jco.2018.36.18_suppl.lba3503

GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study

Olivier Gléhen, Guillaume Passot, Laurent Villeneuve, Delphine Vaudoyer, Sylvie Bin-Dorel et al. (8 authors)

BMC Cancer2014-03-14212 citations

10.1186/1471-2407-14-183

Papers published before 2008-02-04 may not appear yet. Historical indexing is in progress.

Interventions

DRUGfluorouracil

Given IV

DRUGleucovorin calcium

Given IV

DRUGoxaliplatin

Given during surgery

PROCEDUREhyperthermia treatment

Given intraperitoneally during surgery

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed colorectal cancer * Peritoneal carcinoma extension ≤ 25 (Sugarbaker Index) (determined intraoperatively) * Planning to receive standard systemic chemotherapy * Chemotherapy for metastatic cancer should be initiated 3 months after surgery * No extraperitoneal metastases, including liver and lung metastasis * No carcinomatosis of other origin besides colorectal, in particular appendical carcinomatosis * Macroscopically complete resection (R1) or surgical reduction of tumor to a residual thickness ≤ 1 mm (R2) is possible PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Life expectancy \> 12 weeks * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 3 times ULN * Alkaline phosphatase ≤ 3 times ULN * Creatinine ≤ 1.25 times ULN * Eligible for surgery * No peripheral neuropathy \> grade 3 * Not pregnant or nursing * No other cancer in the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix * No inability to submit to follow-up medical testing for geographical, social, or psychological reasons * Affiliated with a social security program * Not deprived of liberty or under supervision PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemohyperthermia * No concurrent participation in another study of first-line therapy for this cancer

Design outcomes

Primary

Measure	Time frame
Overall survival	until 3 years

Secondary

Measure	Time frame
Toxicity by NCI CTCAE v.3.0	until 5 years after surgery
Recurrence-free survival	until 3 years
Morbidity from surgical complications (abdominal, extra-abdominal, aplasia)	until 2 months after surgery

Countries

France

Outcome results

None listed