Pilot Study of Hyperthermic Peritoneal Perfusion (HIPEC) for Adolescent and Young Adults With Desmoplastic Small Round Cell Tumor

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01277744
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arm: 1
• Actual Duration (Months): 81.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if heated intra-abdominal cisplatin can help to control abdominal tumors in patients having surgery to remove the tumors. The safety of this drug will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancers; Sarcoma	Procedure: Hyperthermic Peritoneal Perfusion (HIPEC); Drug: Cisplatin	Phase 2

Detailed Description

The Study Drugs:

Cisplatin has a platinum atom at its center. The platinum is supposed to poison the cancer cells, which may cause them to die.

Surgery and Study Drug Administration:

If you are found to be eligible, the abdominal surgery will be performed to try to remove as many tumors as possible. The abdominal surgery is not being performed specifically for this research study and would be performed even if you didn't take part in this study. You will be given a separate consent form to sign that explains the details and risks of abdominal surgery in more detail.

During the surgery you will receive sodium thiosulfate by vein. The abdomen will then be temporarily closed. Then the abdominal wash will begin. During the "abdominal wash," heated cisplatin will be delivered through plastic tubing that is connected to a pump into the abdomen. The pump pushes the heated cisplatin into the abdomen and then pulls it out and recirculates the cisplatin. The skin of the abdomen is temporarily closed during the abdominal wash. The surgeon will also "wash" over the closed area of the surgical site. A pump will be used to pump heated cisplatin in and out of the abdomen over 90 minutes while the surgeon gently presses on the abdominal wall so the cisplatin reaches all areas in the abdomen. After 90 minutes, the cisplatin is removed and the abdomen will be "washed" with saline and all fluid will be removed before the surgeon permanently closes the abdomen with 3 layers of stitches.

Two (2) pea-sized tumor samples will be sent to the laboratory of Dr. Dina Lev for tissue evaluation and extraction of RNA (genetic material). One (1) tumor sample will be removed before the procedure and the other sample will be removed at the end of the procedure. The samples will be examined under a microscope and DNA (the genetic material in cells) will be removed to look for any changes to the DNA. The results of these tests will not be shared with you, nor will they be used for any decisions regarding your treatment. The samples will be destroyed after these tests are complete.

There is a chance that the surgeon may decide during the surgery that the abdominal wash will not be performed, for example if the disease has spread to or attached to certain organs. If this occurs, your doctor will discuss other treatment options with you.

Study Visits:

On Days 1-5, 11, and 14, (Day 1 being the day after surgery):

• Blood (about 1 teaspoon) will be drawn for routine tests.

• You will have a physical exam, including measurement of your weight and vital signs.

Follow-Up Visits:

About 1, 3, and 6 months after the surgery is complete, you will have follow-up visits and the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your weight and vital signs.

• Blood (about 1 teaspoon) will be drawn at the 1 month visit only for routine tests.

• You will have a hearing test at the 1 month visit only.

• Blood (about 3 teaspoons) will be drawn for routine tests at the 3 and 6 month visits only.

• At the 3 and 6 month visits only, you will have a CT scan, positron emission tomography (PET)-CT scan, or MRI scan to check the status of the disease.

Length of Study:

You will remain on study for up to 6 months. You will be taken off study if the disease gets worse.

If the study doctor learns that the disease has come back or gotten worse at the 6 month follow-up visit, you may be eligible for a re-perfusion, which is a repeat of the operation and study drug administration. If you are eligible for a re-perfusion, your participation on this study will end and then you will be given a new consent form to sign in order to be re-enrolled back onto this study.

This is an investigational study. Cisplatin is FDA-approved and commercially available for the treatment of advanced bladder cancer, metastatic testicular cancer, metastatic ovarian cancer, hepatoblastoma, neuroblastoma, metastatic appendiceal cancer, and abdominal mesothelioma. The use of cisplatin in patients with abdominal sarcoma-type tumors is investigational.

Up to 22 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Hyperthermic Peritoneal Perfusion (HIPEC) for Adolescent and Young Adults With Desmoplastic Small Round Cell Tumor and Other Non-Carcinomas
• Actual Study Start Date: May 9, 2011
• Actual Primary Completion Date: Feb 16, 2018
• Actual Study Completion Date: Feb 16, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: HIPEC + Cisplatin HIPEC, technique for combining hyperthermia and chemotherapeutic agents delivered intraoperatively to the peritoneal and retroperitoneal surface via a recirculating perfusion circuit, performed after cytoreductive surgery and lysis of adhesions. Cisplatin 100 mg/M2 per perfusion catheter. The perfusion is continued for 90 minutes after adding the Cisplatin.

Procedure: Hyperthermic Peritoneal Perfusion (HIPEC); HIPEC, technique for combining hyperthermia and chemotherapeutic agents delivered intraoperatively to the peritoneal and retroperitoneal surface via a recirculating perfusion circuit, performed after cytoreductive surgery and lysis of adhesions.; Drug: Cisplatin; 100 mg/M2 per perfusion catheter. The perfusion is continued for 90 minutes after adding the cisplatin.; Other Names: Platinol-AQ Platinol CDDP

Outcome Measures

Primary Outcome Measures

1. Recurrence Free Survival [36 months after the last participant enrolled]

   Date of surgery to date of death or date of recurrence, whichever occurred first for patients who experienced an event, and to date of last follow-up for patients alive without recurrence

Secondary Outcome Measures

1. Overall Survival [From the date of diagnosis to the date of death or last follow up date for patient alive up to 81 months]

   From the date of diagnosis to the date of death or last follow up date for patient alive.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age greater than or equal to 1 years

2. Histologically or genetically proven diffuse peritoneal or retroperitoneal tumor from desmoplastic round cell tumor, ovarian germ cell, sarcoma, Wilms' tumor, or other non-carcinoma tumors.

3. Radiologic workup must demonstrate that the disease is confined to the abdominal cavity

4. Radiologic workup or prior abdominal exploration must be consistent with disease which can be debulked to a residual size of less than or equal to 1 cm thickness per tumor deposit

5. Patients must have a minimum expected duration of survival of greater than 6 weeks as determined and documented by the attending surgeon or medical oncologist.

6. Patients must not have any systemic illness which precludes them from being an operative candidate as determined by anesthesia preoperative evaluation. This includes but is not limited to, sepsis, liver failure, pregnant or lactating females.

7. Patients must have fully intact mental status and normal neurologic abilities. Intact mental status is defined by 'the capacity to identify and recall one's identity and place in time and space.' Assessment of mental status and documentation of fully intact mental status will be completed using physical and mental exam by the referring doctor or oncologist.

8. Patients must have adequate renal function (serum creatinine </= 1.5 mg/dl without history dialysis or renal failure or creatinine clearance less than 50 mL/min/1.73M^2 if less than 5 years of age)

9. Patients will be eligible if the white blood cell count (WBC) is >/=2000/microliter or absolute neutrophil count (ANC) is >/=1,500 and platelets are >/= 100,000/mm^3

10. Patients will be eligible if serum total bilirubin and liver enzymes are </=2 times the upper limit of normal

11. Patients must be recovered from any toxicity from all prior chemotherapy, immunotherapy, or radiotherapy and be at least 14 days past the date of their last treatment

Exclusion Criteria:

1. Patients will be ineligible if they have any concomitant cardiopulmonary disease which would place them at unacceptable risk for a major surgical procedure

2. Patients will be ineligible if they have disease outside of the abdominal cavity which is uncontrolled

3. Patients will be ineligible if they have a baseline neurologic toxicity of Grade 3 or greater (because of the potential neurotoxicity associated with platinum)

4. Patients who have failed previous intraperitoneal platinum therapy will be ineligible

5. Patients with Retroperitoneal Liposarcoma will be ineligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Andrea Hayes-Jordan, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 14, 2013

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01277744
• Other Study ID Numbers: 2009-0528; NCI-2011-00245
• First Posted: Jan 17, 2011
• Last Update Posted: Jan 13, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Desmoplastic small round cell tumor; DSRCT; Hyperthermic peritoneal perfusion; HIPEC; Complete abdominal tumor excision; Extensive abdominal disease; Non-carcinoma tumors; Abdominal cavity; Cisplatin; Platinol-AQ; Platinol; CDDP; Diffuse peritoneal tumor; Retroperitoneal tumor; Ovarian germ cell; Wilms' tumor
• Additional relevant MeSH terms: Desmoplastic Small Round Cell Tumor; Hyperthermia; Fever; Cisplatin

Study Results

Participant Flow

Recruitment Details	Recruitment Details: May 2011 to December 2013
Pre-assignment Detail	One patient was enrolled twice; she received a second hyperthermic intraperitoneal chemotherapy surgery after she recurred following the first procedure

Arm/Group Title	HIPEC
Arm/Group Description	HIPEC with Cisplatin
Period Title: Overall Study
STARTED	22
COMPLETED	20
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	HIPEC
Arm/Group Description	HIPEC with Cisplatin
Overall Participants	22
Age (Count of Participants)
<=18 years	14 63.6%
Between 18 and 65 years	8 36.4%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	7 31.8%
Male	15 68.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	16 72.7%
More than one race	0 0%
Unknown or Not Reported	6 27.3%
Region of Enrollment (participants) [Number]
United States	21 95.5%
Russia	1 4.5%

Outcome Measures

1. Primary Outcome

Title	Recurrence Free Survival
Description	Date of surgery to date of death or date of recurrence, whichever occurred first for patients who experienced an event, and to date of last follow-up for patients alive without recurrence
Time Frame	36 months after the last participant enrolled

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HIPEC
Arm/Group Description	HIPEC with Cisplatin
Measure Participants	20
Median (95% Confidence Interval) [months]	13.99

2. Secondary Outcome

Title	Overall Survival
Description	From the date of diagnosis to the date of death or last follow up date for patient alive.
Time Frame	From the date of diagnosis to the date of death or last follow up date for patient alive up to 81 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HIPEC
Arm/Group Description	HIPEC with Cisplatin
Measure Participants	20
Median (95% Confidence Interval) [months]	58.4

Adverse Events

Time Frame	6 months post surgery
Arm/Group Title	HIPEC
Arm/Group Description	HIPEC with Cisplatin
All Cause Mortality
	HIPEC
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	HIPEC
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	HIPEC
	Affected / at Risk (%)	# Events
Total	18/20 (90%)
Gastrointestinal disorders
Neurogenic bladder	3/20 (15%)
Enterocutaneous fistula	1/20 (5%)
Infections and infestations
Urinary tract infection	2/20 (10%)
Wound infection	1/20 (5%)
Investigations
Creatinine increased	2/20 (10%)
White blood cell decreased	14/20 (70%)
Platelet count decreased	15/20 (75%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.