PIPAC for the Treatment of Peritoneal Carcinomatosis in Patients With Ovarian, Uterine, Colorectal, or Gastric Cancer
Keywords
Abstract
Description
PRIMARY OBJECTIVE:
I. To evaluate the safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in 2 groups of patients with peritoneal carcinomatosis (PC), either due to primary ovarian, uterine, or gastric carcinoma (Arm 1) or to primary colorectal carcinoma (Arm 2), based on treatment-related adverse events reported by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
SECONDARY OBJECTIVES:
I. Efficacy will be assessed by:
Ia. Response Evaluation Criteria in Solid Tumors (RECIST), if available, version 1.1 via computed tomography (CT) scan at baseline, following the second cycle (week 10), and 6 weeks after completing treatment (at 18 weeks/off study).
Ib. Peritoneal regression grading score (PRGS) via biopsy at each cycle (both preoperative and postoperative peritoneal samples will be obtained).
Ic. Peritoneal carcinomatosis index (PCI) at the time of laparoscopy. II. Post-operative surgical complications by Claven-Dindo classification evaluated at 4, 10, and 16 weeks (4 weeks after each PIPAC).
III. Progression-free survival. IV. PIPAC technical failure rate. V. Patient-reported health state/quality of life and symptoms before treatment and at 6, 12, and 18 weeks/off study, as measured by the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L) and MD Anderson Symptom Inventory (MDASI).
VI. Functional status, as measured by the number of daily steps before and after treatments (Vivofit 4 wristband pedometer - Garmin Company).
EXPLORATORY OBJECTIVE:
I. Correlative/translational studies to characterize the tumor microenvironment, subclonal evolution, genomics, and pharmacokinetics of peritoneal tumors.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with cisplatin, followed by doxorubicin. Treatment repeats every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients with colorectal cancer undergo PIPAC with oxaliplatin. For cycles 2 and 3, patients receive leucovorin intravenously (IV) over 10 minutes and fluorouracil IV over 15 minutes 1-24 hours before undergoing PIPAC. Treatment repeats every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for up to 3 years.
Dates
| Last Verified: | 02/29/2020 |
| First Submitted: | 03/12/2020 |
| Estimated Enrollment Submitted: | 03/29/2020 |
| First Posted: | 03/31/2020 |
| Last Update Submitted: | 07/25/2020 |
| Last Update Posted: | 07/27/2020 |
| Actual Study Start Date: | 08/31/2020 |
| Estimated Primary Completion Date: | 03/07/2022 |
| Estimated Study Completion Date: | 03/07/2022 |
Condition or disease
Intervention/treatment
Drug: Arm I (PIPAC, cisplatin, doxorubicin)
Drug: Arm I (PIPAC, cisplatin, doxorubicin)
Drug: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)
Procedure: Intraperitoneal Chemotherapy
Drug: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)
Drug: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Device: Nebulizer with High-Pressure Injector
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Arm I (PIPAC, cisplatin, doxorubicin) Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with cisplatin, followed by doxorubicin. Treatment repeats every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. | Drug: Arm I (PIPAC, cisplatin, doxorubicin) Given via PIPAC |
| Experimental: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) Patients with colorectal cancer undergo PIPAC with oxaliplatin. For cycles 2 and 3, patients receive leucovorin IV over 10 minutes and fluorouracil IV over 15 minutes 1-24 hours before undergoing PIPAC. Treatment repeats every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. | Drug: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) Given IV |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Documented informed consent of the participant and/or legally authorized representative - Patients must have histologically confirmed ovarian, uterine, gastric, or colorectal cancer with peritoneal metastases - Prior intraperitoneal chemotherapy is permitted - Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 - Absolute neutrophil count (ANC) >= 1500/mm^3 - Platelets >= 100,000/mm^3 - Hemoglobin >= 9g/dl - Serum total bilirubin =< 1.5 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x ULN, unless liver metastases are present or unless patients i know to have chronic liver disease (hepatitis) in which case AST and ALT must be =< 5 x ULN - Alkaline phosphatase =< 2 x ULN - Serum creatinine (sCr) =< 1.5 x ULN, or creatinine clearance (Ccr) >= 40 ml/min as calculated by the Cockcroft-Gault formula - No contraindications for a laparoscopy - The peritoneal disease dose not have to be measurable by RECIST 1.1 but needs to be visible on cross sectional imaging or diagnostic laparoscopy - Patients must have progressed on at least one evidence-based chemotherapeutic regimen - For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated - Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load - Women of childbearing potential (WOCBP) and male patients with WOCBP partner must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is define as: - Amenorrhea >= 12 consecutive months without cause or - For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vagina products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential - INCLUSION TO PROCEED WITH PIPAC: Laparoscopy findings must meet all of the below criteria in order to proceed to PIPAC: - PIPAC access is feasible - There is room for aerosol therapy - There is no evidence of impending bowel obstruction - =< 5 L of ascites - Not a candidate for cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) Exclusion Criteria: - Gastric and colorectal: - Extra-peritoneal metastatic disease - Arm 1 (ovarian, uterine, gastric): - Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones - Arm 2 (colorectal): - Known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency - Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition - Prior unanticipated severe reaction or hypersensitivity to platinum based compounds - Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia, hearing loss, or non-clinically significant laboratory abnormalities. Grade 2 peripheral neuropathy is permitted - Life expectancy of less than 6 months - Chemotherapy or surgery within the last 4 weeks prior to enrollment (6 weeks for prior bevacizumab therapy). Five half-lives for other anti-cancer agents - Previous anaphylactic reaction to the chemotherapy drug used - Patients may not be receiving any other investigational or concurrent anti-cancer agents - Ascites due to decompensated liver cirrhosis; portal vein thrombosis - Simultaneous tumor debulking with gastrointestinal resection - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, severe renal impairment, myelosuppression, or severe hepatic impairment - Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system - Involvement in the planning and conduct of the study - Pregnancy - Untreated central nervous system (CNS) metastases; patients whose CNS metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable may be enrolled - Patients with psychiatric illness/social situations that would limit compliance with study requirements - New York Heart Association (NYHA) class 3 or 4; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months - Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug - Exclusive total parenteral nutrition - Prior intra-abdominal aerosol chemotherapy |
Outcome
Primary Outcome Measures
1. Dose limiting toxicities (DLTs) [Up to 18 weeks]
Secondary Outcome Measures
1. Incidence of adverse events [Start of treatment until week 18]
2. Percentage of evaluable patients who have achieved complete response (CR), partial response (PR), or stable disease (SD) [At baseline, week 10, and 6 weeks after completing treatment (at 18 weeks/off-study)]
3. Percentage of evaluable patients who have achieved CR, PR, or SD [At the time of laparoscopy (or CT imaging if laparoscopy is not planned during surgery)]
4. Percentage of evaluable patients who have achieved a decrease in Peritoneal Regression Grading Score (PRGS) over successive biopsies [Up to 18 weeks]
5. Progression-free survival [Time from first pressurized intraperitoneal aerosolized chemotherapy (PIPAC) procedure, assessed up to 1 year]
6. Number of post-surgical complications [At 4 weeks after each PIPAC]
7. PIPAC technical failure rate [Up to 3 years]
8. Patient-reported health state/quality of life and symptoms [Before treatment, and at 6, 12, and 18 weeks/off study]
9. Functional status [Up to 18 weeks]
