A Phase II Study of Surgical Debulking With Peritonectomy and Biweekly Intraperitoneal 5FU With Systemic Oxaliplatin/5FU/Leucovorin in Patients With Pseudomyxoma Peritonei or Peritoneal Carcinomatosis

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00352755
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study prospectively evaluates a multidisciplinary approach to patients with intraperitoneal carcinomatosis at Washington University. Patients with peritoneal carcinomatosis or pseudomyxoma peritonei will undergo debulking surgery with peritonectomy and placement of adhesive barrier film followed by repeated delayed intraperitoneal chemotherapy with 5FU with systemic oxaliplatin-based chemotherapy on a biweekly schedule. A retrospective review of patients treated in a similar manner at our institution showed good tolerance and efficacy. This formal Phase II study is planned to determine the safety, toxicities and survival of patients with peritoneal carcinomatosis and pseudomyxoma peritonei treated with this regimen.

Condition or Disease	Intervention/Treatment	Phase
Peritoneal Neoplasms	Procedure: Surgical debulking with peritonectomy; Drug: Intraperitoneal 5FU; Drug: FOLFOX	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Surgical Debulking With Peritonectomy and Biweekly Intraperitoneal 5FU With Systemic Oxaliplatin/5FU/Leucovorin in Patients With Pseudomyxoma Peritonei or Peritoneal Carcinomatosis
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Peritonectomy + IP5FU + FOLFOX Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.

Procedure: Surgical debulking with peritonectomy; Drug: Intraperitoneal 5FU; Other Names: Fluorouracil Efudex ; Drug: FOLFOX; Other Names: Oxaliplatin Fluorouracil Efudex Leucovorin USAN

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events [30 days after end of treatment]

Secondary Outcome Measures

1. Progression Rate [Median follow-up was 32 months]

   -Progressive disease - at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

2. Number of Participants Who Experience Surgical Complications Associated With This Regimen [Median follow-up was 32 months]

3. Progression-free Survival [Median follow-up was 32 months]

4. Overall Survival [Median follow-up was 32 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Eligibility Criteria:

• Histological Diagnosis: Patients must have a histologically documented pseudomyxoma peritonei or peritoneal carcinomatosis from colorectal/appendiceal and small intestinal adenocarcinoma.

• Patients may have prior chemotherapy.

• Age: Patients must be greater than or equal to 18 years old. Because no dosing or toxicity data are currently available on the use of oxaliplatin in patients <18 years of age, children are excluded from this study, but will be eligible for other pediatric Phase I single-agent trials, when available.

• Performance Status: ECOG 0-2.

• Life Expectancy: greater than 8 weeks.

• Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.

• Hematological Status: Patients must have adequate bone marrow function defined as an absolute neutrophil count greater than or equal to 1,500/mm3, platelet count greater than or equal to 100,000/mm3 and hemoglobin greater than or equal to 8 g/dl.

• Hepatic Function: Total bilirubin must be less than or equal to institutional upper limit of normal (ULN). Transaminases (SGOT and/or SGPT) may be up to 2.5 X ULN if alkaline phosphatase is less than or equal to ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are less than or equal to ULN. However, patients who have both transaminase elevation greater than 1.5 x ULN and alkaline phosphatase greater than 2.5 x ULN are not eligible for the study.

• Renal Function: Patients must have adequate renal function defined as serum creatinine less than or equal to 2.0 mg/dl or creatinine clearance greater than or equal to 60 ml/min/1.73 m2 for patients with creatinine levels above 2.0 mg/dl.

• Sexually Active Patients: For all sexually active patients, the use of adequate barrier contraception (hormonal or barrier method of birth control) will be required during therapy, prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential. Pregnant and nursing women patients are not eligible.

• HIV-Positive Patients: Patients receiving anti-retroviral therapy (HAART) for HIV infection are excluded from the study because of possible pharmacokinetic interactions. Appropriate studies will be undertaken in patients receiving HAART therapy, when indicated.

• Informed Consent: After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.

• Inclusion of Women and Minorities: Entry to this study is open to both men and women and to all racial and ethnic subgroups.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	St. Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: James Fleshman, M.D., Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00352755
• Other Study ID Numbers: 06-0312
• First Posted: Jul 17, 2006
• Last Update Posted: Dec 13, 2016
• Last Verified: Oct 1, 2016

• Additional relevant MeSH terms: Carcinoma; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Leucovorin; Fluorouracil; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Period Title: Overall Study
STARTED	18
COMPLETED	16
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Overall Participants	18
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	12 66.7%
Male	6 33.3%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events
Time Frame	30 days after end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Measure Participants	18
Hemoglobin	1 5.6%
Leukocytes	1 5.6%
Lymphopenia	3 16.7%
Neutrophils	2 11.1%
Rigors/chills	1 5.6%
Dehydration	2 11.1%
Nausea	3 16.7%
Vomiting	2 11.1%
Febrile neutropenia	1 5.6%
Anal/perianal infection	1 5.6%
Urinary infection	1 5.6%
Infection (clinic or micro) with Gr. 3/4 ANC	1 5.6%
Wound infection	2 11.1%
Alanine aminotransferase (ALT)	1 5.6%
Creatinine	1 5.6%
Hypermagnesemia	1 5.6%
Hypocalcemia	1 5.6%
Hypokalemia	2 11.1%
Hypomagnesemia	1 5.6%
Hyponatremia	2 11.1%
Syncope	1 5.6%
Abdomen pain	3 16.7%
Head/headache pain	1 5.6%

2. Secondary Outcome

Title	Progression Rate
Description	-Progressive disease - at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	Median follow-up was 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Measure Participants	16
Number [percentage of participants]	62.5 347.2%

3. Secondary Outcome

Title	Number of Participants Who Experience Surgical Complications Associated With This Regimen
Time Frame	Median follow-up was 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Measure Participants	16
Number [participants]	9 50%

4. Secondary Outcome

Title	Progression-free Survival
Time Frame	Median follow-up was 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Measure Participants	16
Median (Full Range) [months]	21.20

5. Secondary Outcome

Title	Overall Survival
Time Frame	Median follow-up was 32 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
Measure Participants	16
Median (Full Range) [months]	32.01

Adverse Events

Arm/Group Title	Peritonectomy + IP5FU + FOLFOX
Arm/Group Description	Surgical debulking with peritonectomy IP 5FU 600 mg/m2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles. FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m2 over 2 hours with leucovorin at 400 mg/m2 and IV 5-FU at 2400 mg/m2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.
All Cause Mortality
	Peritonectomy + IP5FU + FOLFOX
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Peritonectomy + IP5FU + FOLFOX
	Affected / at Risk (%)	# Events
Total	3/18 (16.7%)
Gastrointestinal disorders
Nausea	1/18 (5.6%)
Vomiting	1/18 (5.6%)
General disorders
Fatigue	1/18 (5.6%)
Fever	2/18 (11.1%)
Rigors/chills	2/18 (11.1%)
Infections and infestations
Infection - wound	1/18 (5.6%)
Metabolism and nutrition disorders
Dehydration	1/18 (5.6%)
Other (Not Including Serious) Adverse Events
	Peritonectomy + IP5FU + FOLFOX
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Hemoglobin	10/18 (55.6%)
Cardiac disorders
Atrial fibrillation	1/18 (5.6%)
Chest/thorax pain	2/18 (11.1%)
Eye disorders
Blurred vision	1/18 (5.6%)
Gastrointestinal disorders
Abdominal pain	8/18 (44.4%)
Constipation	2/18 (11.1%)
Diarrhea	6/18 (33.3%)
Gastrointestinal, other	2/18 (11.1%)
Ileus	1/18 (5.6%)
Mucositis	1/18 (5.6%)
Nausea	7/18 (38.9%)
Oral cavity	1/18 (5.6%)
Vomiting	7/18 (38.9%)
General disorders
Fatigue	7/18 (38.9%)
Injection site reaction	1/18 (5.6%)
Pain	3/18 (16.7%)
Rigors/chills	2/18 (11.1%)
Infections and infestations
Febrile neutropenia	1/18 (5.6%)
Infection - Anal/Perianal	1/18 (5.6%)
Infection - Kidney	2/18 (11.1%)
Infection - Oral - Cavity, gums	1/18 (5.6%)
Infection - Urinary	1/18 (5.6%)
Infection with Gr.3/4 neutrophils	1/18 (5.6%)
Wound infection	3/18 (16.7%)
Injury, poisoning and procedural complications
Wound complication, non-infectious	1/18 (5.6%)
Investigations
ALT	7/18 (38.9%)
AST	7/18 (38.9%)
Alkaline phosphatase	5/18 (27.8%)
Bilirubin	1/18 (5.6%)
Creatinine	2/18 (11.1%)
Hematocrit	2/18 (11.1%)
Leukocytes	5/18 (27.8%)
Lymphopenia	6/18 (33.3%)
Neutrophils	4/18 (22.2%)
Platelets	6/18 (33.3%)
Thrombocytopenia	1/18 (5.6%)
Metabolism and nutrition disorders
Anorexia	3/18 (16.7%)
Dehydration	2/18 (11.1%)
Hyperglycemia	2/18 (11.1%)
Hyperkalemia	1/18 (5.6%)
Hypermagnesemia	1/18 (5.6%)
Hypernatremia	1/18 (5.6%)
Hypoalbuminemia	1/18 (5.6%)
Hypocalcemia	2/18 (11.1%)
Hypoglycemia	2/18 (11.1%)
Hypokalemia	2/18 (11.1%)
Hypomagnesemia	2/18 (11.1%)
Hyponatremia	2/18 (11.1%)
Metabolic - Other	1/18 (5.6%)
Musculoskeletal and connective tissue disorders
Muscle pain	2/18 (11.1%)
Musculoskeletal - Other	2/18 (11.1%)
Nervous system disorders
Head/headache	1/18 (5.6%)
Neuropathy - sensory	7/18 (38.9%)
Syncope (fainting)	1/18 (5.6%)
Psychiatric disorders
Depression	2/18 (11.1%)
Insomnia	2/18 (11.1%)
Reproductive system and breast disorders
Sexual - other	2/18 (11.1%)
Vaginal perforation	1/18 (5.6%)
Respiratory, thoracic and mediastinal disorders
Hiccoughs	1/18 (5.6%)
Nose bleed	1/18 (5.6%)
Skin and subcutaneous tissue disorders
Rash/desquamation	1/18 (5.6%)
Skin breakdown/decubitus ulcer	1/18 (5.6%)
Vascular disorders
Hot flashes	1/18 (5.6%)
Phlebitis	1/18 (5.6%)

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.