Adjuvant HIPEC to Prevent Colorectal Peritoneal Metastases in High-risk Patients

NCT02575859 | Completed Phase 1

• 1 other identifier: 35/13
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant HIPEC has not yet been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of HIPEC performed simultaneously with primary curative surgery in colorectal cancer patients with primary tumor-related risk-factors for the development of metachronous peritoneal metastases.

Conditions

Colorectal Neoplasm; Metastasis

Keywords

HIPEC; peritoneal lavage

Outcome Measures

Primary Outcomes (1)

• Positive predictive value of preoperative/intraoperative assessment of primary tumor-related risk factors for the development of metachronous peritoneal metastases in patients undergoing curative surgery for colorectal cancer.

  The presence versus absence of primary tumor-related risk-factors for the development of metachronous peritoneal metastases, as assessed during the preoperative/intraoperative phase, is compared with the findings of the pathological examination of surgical specimens.

  The primary outcome measure is assessed at an average of one week after the operation, at the time the pathological examination of surgical specimens is expected to be completed.

Secondary Outcomes (2)

• Number of patients with postoperative treatment-related adverse events.

  60 days

• Peritoneal progression-free survival

  36 months

Other Outcomes (2)

• Overall survival

  36 months

• Progression-free survival

  36 months

Study Arms (2)

Adjuvant HIPEC

EXPERIMENTAL

Adjuvant HIPEC will be performed simultaneously with primary tumor resection in patients undergoing curative surgery for primary colorectal cancer associated with risk factors for the development of metachronous peritoneal metastases.

Drug: adjuvant HIPEC; Procedure: surgery

Matched control

NO INTERVENTION

Comparable controls will be retrospectively selected from patients undergoing curative surgery for colorectal cancer at the National Cancer Institute (Milan, Italy) during the same period. Every single control patient will be matched with a.patient in HIPEC group according to the following criteria: i) risk-factor for metachronous PM (minimal synchronous PM vs. ovarian metastases vs. pathological tumor \[pT\] stage (pT4a/b); ii) pathological node (pN) stage (pN0 vs. pN1/2); iii) grading (well/moderately vs. poorly differentiated); iv) histological subtype (adenocarcinoma vs. mucinous/signet ring cell carcinoma); v) sex; vi) age (+/-5 years). The investigators will be blinded to patient outcomes during the process.

Interventions

adjuvant HIPEC DRUG

Closed-abdomen HIPEC with cisplatin (25 mg/m2/l of perfusate) and mitomycin-C (3•3 mg/m2/l of perfusate) at 42•5°C for 60 minutes. Perfusate volume: 4-6 l.

Also known as: Cisplatin, mitomycin-C

Adjuvant HIPEC

surgery PROCEDURE

Colon resections for primary tumors were performed according to the oncologic principles of adequate lymph-adenectomy. Complete adhesiolysis, resection of falciform hepatic ligament, greater and lesser omentectomy were performed in all patients to ensure optimal perfusion during the HIPEC. Tumor deposits on visceral and parietal surfaces were surgically removed by formal peritonectomy procedures and/or organ resections, as needed.

Adjuvant HIPEC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• pathologically confirmed colorectal carcinoma;
• curative surgery;
• presence of at least one of the following risk-factors for the development of metachronous PM:
• minimal synchronous PM (nodules ≤1cm in the omentum and/or close to the primary tumor), completely resected at the same time as primary tumor;
• synchronous ovarian metastases, also resected at the same time as primary tumor;
• primary tumor either penetrating visceral peritoneum (T4a),
• primary tumor directly invading other organs (T4b);
• signature of an informed consent form.
• intention to start adjuvant systemic therapy and postoperative follow-up;
• performance status ≤2 according to the Eastern Cooperative Oncology Group score;
• no significant co-morbidities.
• no active sepsis
• no impaired cardiac function (history of previous cardiac failure, or ejection fraction \<40%)
• no impaired renal function (serum creatinin \> 1.5 normal value or creatinin clearance \< 60 mL/min);
• no impaired hepatic function (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, bilirubin \> 1.5 normal value);

You may not qualify if:

• extensive PM (nodules \>1cm, and/or nodules outside the omentum and/or beyond the close vicinity of the primary tumor);
• extra-abdominal/hepatic metastases;
• emergency presentation (bleeding, perforated, or occlusive primary);
• bleeding diathesis or coagulopathy
• history of previous neoplasm during the past three years, excluding skin spinocellular/basocellular carcinoma;
• preoperative pelvic radio-chemotherapy

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Azienda Usl di Bologna: collaborator

Related Publications (2)

• Virzi S, Iusco D, Baratti D, Bonomi S, Grassi A, Kusamura S, Deraco M. Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases. Tumori. 2013 Sep-Oct;99(5):589-95. doi: 10.1177/030089161309900505.

  PMID: 24362862 RESULT

• Baratti D, Kusamura S, Iusco D, Gimondi S, Pietrantonio F, Milione M, Guaglio M, Bonomi S, Grassi A, Virzi S, Leo E, Deraco M. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the Time of Primary Curative Surgery in Patients with Colorectal Cancer at High Risk for Metachronous Peritoneal Metastases. Ann Surg Oncol. 2017 Jan;24(1):167-175. doi: 10.1245/s10434-016-5488-5. Epub 2016 Aug 12.

  PMID: 27519353 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Cisplatin; Mitomycin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Marcello Deraco, MD

  Fondazione IRCCS Istituto Nazionale Tumori, Milano

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: October 15, 2015
• Study Start: January 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: December 1, 2011
• Last Updated: October 15, 2015

Record last verified: 2015-09