Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02463877 |
| Other study ID # |
Minimally-Invasive |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
October 2014 |
| Est. completion date |
April 30, 2022 |
Study information
| Verified date |
September 2022 |
| Source |
University of California, San Diego |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to determine the feasibility of surgical techniques involving
minimal entry into the living body approach for tumor reduction and treatment in which highly
concentrated anticancer drugs are put directly into the abdomen through a tubes (HIPEC), and
to determine if this approach may improve short-term postoperative outcomes, including the
development of complications related to surgery within the first 30 days after surgery.
Participation in this study is entirely voluntary. Approximately 30 subjects will take part
in this single-center study and all will be enrolled at University of California San Diego.
Description:
Potential patients will be prospectively identified prior to the time of operation based on
the inclusion/exclusion criteria . Those who meet the eligibility criteria and sign consent
will undergo laparoscopy. During laparoscopy, the peritoneal cancer index (PCI) will be
determined for all patients. The PCI is a scoring system that was developed to standardize
the assessment of disease burden. PCI is determined by assigning a Lesion size score (LSS) to
each of the 13 peritoneal regions and then summing the scores (defined further below). Those
with a PCI of ≤10 will continue with laparoscopic cytoreduction and HIPEC. Patients with a
PCI of >10 will have an open cytoreduction and HIPEC. The Investigators plan to enroll 30
patients, though the investigators estimate 18 will ultimately undergo laparoscopic
cytoreduction and HIPEC.
Trial Design:
- Stage 1 will enroll 9 patients, and if 2 or less patients experience postoperative
complications within 30 days of HIPEC the investigators will proceed to stage 2. If 3 or
more patients experience postoperative complications the investigators will terminate
the trial early secondary to futility.
- Stage 2 will enroll 9 additional patients, and if the investigators have 4 or less
patients with postoperative complications out of the total 18 patients the investigators
will reject the null hypothesis.
Visit 1- screening
- History and physical examination
- Routine blood tests standard for monitoring of patient's disease include a complete
blood count, kidney and liver chemistries, and tumor markers (CEA and carbohydrate
antigen 19-9 (CA19-9)) if not already performed;
- Imaging tests per standard of care (chest x-ray, CT scan; PET Scan); possibly
laparoscopy or colonoscopy (both scan patients abdomen area); if not performed prior to
consultation at University of California, San Diego (UCSD)
- Electrocardiogram (ECG); thallium heart scan or echocardiogram if history of cardiac
disease (prior Myocardial Infarction, Congestive Heart Failure, angina, cardiomyopathy,
vascular dysfunction and arrhythmia)
Visit 2 - operation/ surgery
- Physical exam and updated medical history
- Routine blood tests
- Laparoscopic exploration prior to cytoreduction, will be performed, per local standard
of care for assessment of PCI.
- HIPEC will be administered per local standard of care..
- A greater omentectomy will be performed routinely in all cases as is done in open
cytoreduction. Greater and lesser omentectomy, omental bursectomy, splenectomy, left and
right upper quadrant and pelvic peritonectomy, cholecystectomy, total abdominal
hysterectomy, low anterior resection and/or gastrectomy will be performed at the
surgeon's discretion based on volume and distribution of peritoneal surface malignancy
with the aim of achieving complete resection of all grossly apparent disease.
- Peritonectomy and organ resection will be performed to achieve optimal cytoreduction
(defined as removal of all gross disease or cytoreduction to gross deposits less than
2.5 mm in thickness).
- If it is determined that optimal cytoreduction cannot be achieved with
minimally-invasive techniques, the procedure will be converted to an open operation.
- Laparotomy -In cases where minimally-invasive optimal cytoreduction is achieved, a small
(4 to 6 cm) laparotomy incision will be made when necessary for organ extraction and a
wound protector will be used. The mini-laparotomy incision will be utilized for
insertion of HIPEC catheters.
- Temporary skin closure will be performed at all port sites and incisions for
closed-HIPEC. Bowel anastomoses and fascial closure of port sites ≥ 1 cm and of
mini-laparotomy incisions will be performed after completion of HIPEC.
- Completeness of cytoreduction will be estimated and recorded using the system shown
below. Intra-peritoneal tubes and drains will be placed at the surgeon's discretion and
the incision closed in the usual fashion.
- After the procedure, the patient will stay in the intensive care unit (ICU) for about
24-48 hours. For at least 4 hours after the procedure the patient will be asked to stay
in bed. The patient will then stay in the hospital for approximately 3-5 days after the
procedure. This is part of the standard of care.
Surgery must start within 8 weeks from time of screening. Surgery must be performed by a
surgeon experienced in cytoreductive and HIPEC surgery who has met the credentialing
requirements of the study.
Pre-perfusion protocol and perfusion circuit set-up and priming:
At the conclusion of cytoreductive surgery, hemodynamic stability of the patient will be
assured and bleeding points controlled per standard of practice. Systemic body temperature
will be monitored. The perfusion system will be assembled per the operator's manual utilizing
sterile technique. The perfusion circuit priming will be with a balanced electrolyte
solution; 1.5% Delflex Peritoneal Dialysis (DPD) solution is preferred. In the absence of
ascites, approximately 3-4 Liters of perfusate is required for the circuit and priming in an
average 70-kg adult. A general guideline is 1.5-2.0 L/m2 perfusate. The perfusate will be
primed, heated to target temperature at the discretion of the operating surgeon and
re-circulated.
After a patient receives their cytoreductive surgery and HIPEC whether by minimal invasive or
open approach, the biohazardous fluid is collected in the chemotherapy waste containers for
disposal.
Placement of inflow and outflow catheters and temperature probes Peritoneal perfusion
catheters and temperature probes will be placed by the operating surgeon in accordance with
standards of practice. Inflow catheter positioning in the sub-diaphragmatic region of the
peritoneal cavity is preferred. Outflow catheter positioning in the pelvis is preferred. This
protocol allows for open delivery of heated chemotherapy at surgeon discretion. Timing of
intestinal reconstruction and formation of stomas will be at surgeon discretion. Sterile pump
lines from the perfusion system will be delivered to the sterile field and the lines will be
filled with perfusate to prevent airlocks. The inflow and outflow tubing will be connected
and the pre-heated perfusate will be allowed to fill the peritoneal cavity. Usually ~3 liters
of solution is required to distend the cavity and achieve desired flow rates.
Recommended anesthetic management and intra-operative physiological monitoring during HIPEC
An epidural catheter may be placed at the discretion of the operating team (anesthesiologist
and surgeon). Broad-spectrum antimicrobial prophylaxis is recommended prior to surgical
incision (specific antibiotic at the discretion of the operating surgeon). Radial arterial
cannulation may be established for arterial-line blood pressure monitoring. A triple lumen
central venous catheter may be placed at the anesthesiologist's discretion. A nasogastric
tude is typically placed to decompress the stomach. A transurethral catheter is placed in the
bladder. During cytoreductive surgery, careful attention to end tidal carbon dioxide, oxygen
saturation and peak airway pressures is made during diaphragmatic stripping assessing for
signs of pneumothorax. The patient's core body temperature may be reduced to 35 degrees
Celsius (95 °F) prior to commencing hyperthermic intraperitoneal chemotherapy. At the start
of the hyperthermic chemotherapeutic infusion, the Bair Hugger may be set to blow ambient air
flow over the patient. Adequate intravenous fluid hydration with crystalloid and/or colloid
prior to initiation of the hyperthermic chemotherapeutic perfusion is important, as systemic
vasodilatation occurs during the perfusion. Urinary output during HIPEC should be maintained
at 0.5-1.0 ml/kg/hr. Clotting time and INR, serum electrolytes, blood gases, and vital signs
are monitored throughout the procedure. Standards of anesthetic practice interventions should
occur when clinically appropriate. Fresh frozen plasma is utilized to maintain INR ≤ 1.5 as
appropriate
- Heated intraoperative intraperitoneal chemotherapy will be delivered as above. At the
completion of the perfusion, the abdomen will be re-explored, residual fluid aspirated,
bleeding points controlled and reconstructive operation completed if not already done
prior to HIPEC (anastomosis with or without diverting stoma).
- Mitomycin C will be the agent administered for patients with primary appendiceal and
colorectal cancers at a dose of 30 mg/kg. For rare cases of primary peritoneal
mesothelioma or ovarian primary tumors, Cisplatin ( 50 mg/m2) or Doxorubicin (15 mg/m2)
may be used. This is the current standard of care and is not specific to this trial
protocol.
Follow up visits- A follow up visit after 2 weeks and 6 weeks of the surgery for physical
exam and updated medical history.
Then every 3 months (+/- 2 weeks) for the first three year, every 6 months for the next 2
years, and yearly thereafter if no evidence of recurrence. The patient will need the
following tests and procedures during routine follow-up visits. These are part of regular
cancer surveillance and care and are not specific to this study.
Physical exam and updated medical history; Pain assessment; Routine blood tests and study
blood tests; Cross-sectional imaging with CT scan or MRI per standard of care
If patients develop symptoms or exam findings warranting cross-sectional imaging at different
time points, imaging will be performed as needed.
Data collected includes demographics (age, gender), past medical history, past surgical
history, weight, body mass index, body surface area, ICU length of stay, hospital length of
stay, IV narcotic requirements, time to return of bowel function, need for and duration of
Nasogastric tube (NGT) decompression, diagnosis, surgical procedures performed, HIPEC agents
administered, operative time, estimated blood loss, and postoperative complications will be
recorded. Postoperative complications are defined according to the validated classification
system proposed by Clavien and colleagues.8 Briefly, a complication is defined as any
deviation from the normal postoperative course. Complications are classified according to the
involved organ system and are graded according to the therapy required to treat the
complication. Grade I complications are deviations from the expected / normal course, but do
not require pharmacologic, surgical, endoscopic, or radiological intervention for treatment.
Grade II complications require pharmacologic intervention, including blood transfusion and
total parenteral nutrition. Grade III complications require surgical, endoscopic, or
radiological intervention. Grade IV complications are defined as life-threatening events
requiring intensive care for management. Grade V complication is defined as death.
For assessment of oncologic outcomes, patients will be followed with clinic visits every 3
months for the first year, then every 6 months for the next 2 years, and yearly thereafter if
no evidence of recurrence. For patients with recurrent disease, data will be collected on:
site of recurrence, date of recurrence, disease status (no evidence of disease, alive with
disease, died from disease, or died of unknown cause), and length of follow-up will be
recorded. This data will be extracted from the patients' medical records for 5 years from the
time of initial Institutional Review Board (IRB) approval.
