Peritoneal Neoplasms
Conditions
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.
Interventions
PROCEDURESurgical debulking with peritonectomy
DRUGIntraperitoneal 5FU
DRUGFOLFOX
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of Participants Who Experience Surgical Complications Associated With This Regimen | Median follow-up was 32 months | — |
| Progression-free Survival | Median follow-up was 32 months | — |
| Overall Survival | Median follow-up was 32 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Peritonectomy + IP5FU + FOLFOX |
|---|---|
| Age, Continuous | 58 years |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Lymphopenia | 3 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Neutrophils | 2 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Rigors/chills | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Dehydration | 2 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Nausea | 3 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Vomiting | 2 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hemoglobin | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Leukocytes | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Febrile neutropenia | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Anal/perianal infection | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Urinary infection | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Infection (clinic or micro) with Gr. 3/4 ANC | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Wound infection | 2 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Alanine aminotransferase (ALT) | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Creatinine | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypermagnesemia | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypocalcemia | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypokalemia | 2 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hypomagnesemia | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Hyponatremia | 2 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Syncope | 1 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Abdomen pain | 3 participants |
| Peritonectomy + IP5FU + FOLFOX | Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events | Head/headache pain | 1 participants |
Secondary
Number of Participants Who Experience Surgical Complications Associated With This Regimen
Time frame: Median follow-up was 32 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peritonectomy + IP5FU + FOLFOX | Number of Participants Who Experience Surgical Complications Associated With This Regimen | 9 participants |
Secondary
Overall Survival
Time frame: Median follow-up was 32 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peritonectomy + IP5FU + FOLFOX | Overall Survival | 32.01 months |
Secondary
Progression-free Survival
Time frame: Median follow-up was 32 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peritonectomy + IP5FU + FOLFOX | Progression-free Survival | 21.20 months |
Secondary
Progression Rate
-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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peritonectomy + IP5FU + FOLFOX | Progression Rate | 62.5 percentage of participants |