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Colorectal NeoplasmPhase 1/2NCT02575859

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

A Phase 1/2 study testing adjuvant HIPEC and surgery in people with Colorectal Neoplasm and Metastasis, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Colorectal Neoplasm, Metastasis
What is being tested?
adjuvant HIPEC and surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
No sites listed yet
Study dates
Jan 2006to Dec 2011
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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),
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  • 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);
  • no impaired bone marrow function (leucocytes < 4000/mm3 ; neutrophils < 1500/mm3; platelet < 80000/mm3)
  • no impaired lung function (diagnosis of severe chronic obstructive pulmonary disease , or forced expiratory volume at one second < 50% or a diffusion capacity of lung for carbon monoxide < 40% age adjusted).

Who cannot join

  • 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

About this study

Official title: Pilot Study of Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Colorectal Cancer at High Risk for the Development of Metachronous Peritoneal Metastases

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.

Read the detailed description

BACKGROUND Peritoneal surfaces are the second most common site of disease progression for colorectal cancer (CRC), following liver metastases. Historically, prognosis of CRC peritoneal metastases (PM) was only about 6 months with palliative systemic chemotherapy or supportive care. Survival improvements have been reported with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, CRS/HIPEC is more effective and safe when early-stage CRC-PM are treated and most patients are not suitable for CRS/HIPEC, due to extensive peritoneal and/or systemic disease. Also, in the palliative setting, modern systemic therapies appear to be less effective for PM, than non-PM metastatic CRC and absence of symptoms and current limitations of imaging hamper early diagnosis and treatment of PM. These points would support the use of adjuvant HIPEC to prevent the outgrowth of occult peritoneal seeding into macroscopic disease.

STUDY DESIGN This tudy to assesses feasibility and safety of an integrated approach of curative surgery and adjuvant HIPEC performed at the same time as primary surgery in patients with primary CRC at high risk for the development of metachronous PM. Patients are prospectively selected on the base of preoperative clinical and radiological work-up. At surgery, careful exploration of all peritoneal the cavity, and intra-operative pathological examination are carried out to confirm clinical-pathological risk-factors for PM development Standard adjuvant systemic chemotherapy is intended in the postoperative setting. A matched control group will be selected among patients with colorectal cancer undergoing curative surgery and standard adjuvant systemic chemotherapy at the same institution and during the same period.

STUDY POPULATION Patients with colorectal cancer undergoing intentionally curative resection for primary tumors infiltrating the visceral serosa (T4a) or directly invading adjacent organs (T4b), with positive peritoneal washing cytology or resected ovarian or minimal peritoneal metastases.

INTERVENTION Adjuvant HIPEC procedure is performed under general anaesthesia after the completion of the surgical procedures. Colon resections for primary tumors are performed according to the oncologic principles of adequate lymph-adenectomy.Greater and lesser omentectomy and adhesiolysis (if necessary) are performed routinely to ensure optimal perfusion during the HIPEC. Tumor deposits on visceral and parietal surfaces are surgically removed by formal peritonectomy procedures and/or organ resections, as needed. HIPEC is performed 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 according to the closed-abdomen .technique.

OUTCOMES Primary end-point is the sensitivity and false positive rate of preoperative/intraoperative assessment of primary tumor-related risk-factors for the development of peritoneal metastases in patients with colorectal cancer undergoing curative surgery..Secondary endpoints are number of participants with adverse events as a measure of safety and tolerability, Cumulative incidence of PM, overall and progression-free survival are assessed in comparison with matched controls.

Being tested
adjuvant HIPEC, surgery
Keywords
HIPEC, peritoneal lavage
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • adjuvant HIPECDrug

    Also called Cisplatin, mitomycin-C

    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.

  • surgeryProcedure or surgery

    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.

Study groups in NCT02575859
Study groupRoleWhat they receive
Adjuvant HIPECExperimentalAdjuvant 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.
Receives: Drug: adjuvant HIPEC; Procedure: surgery
Matched controlNo interventionComparable 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

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

    All-type adverse events occurring within 60 days from surgery and adjuvant HIPEC (including surgical complications and systemic toxicities) will be recorded and graded according to the Common Terminology Criteria for Adverse Events of the National Institute of Health (version 4.0).

    Measured: 60 days

  2. Peritoneal progression-free survival

    Peritoneal progression-free survival is calculated from the day of surgery and HIPEC to the date of death for any cause, or first recurrence involving the peritoneum..

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2015 (estimated)
  2. Study startJan 2006
  3. Primary completionJun 2010
  4. Study completionDec 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02575859
Sponsor's protocol ID
35/13
Status last verified
Sep 2015
First submitted
21 Sep 2015
Last updated
15 Oct 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 24362862

  • 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.

    PubMed 27519353

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing adjuvant HIPEC and surgery in people with Colorectal Neoplasm and Metastasis, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02575859, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2015.

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