Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Ovarian, Uterine, Appendiceal, Colorectal, and Gastric Cancer Patients With Peritoneal Carcinomatosis (PC)
Overview
- Phase
- Phase 1
- Intervention
- Biopsy
- Conditions
- Clinical Stage IV Gastric Cancer AJCC v8
- Sponsor
- City of Hope Medical Center
- Enrollment
- 49
- Locations
- 3
- Primary Endpoint
- Dose limiting toxicities
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This phase I trial studies the side effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treating patients with ovarian, uterine, appendiceal, stomach (gastric), or colorectal cancer that has spread to the lining of the abdominal cavity (peritoneal carcinomatosis). Chemotherapy drugs, such as cisplatin, doxorubicin, oxaliplatin, leucovorin, fluorouracil, mitomycin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PIPAC is a minimally invasive procedure that involves the administration of intraperitoneal chemotherapy. The study device consists of a nebulizer (a device that turns liquids into a fine mist), which is connected to a high-pressure injector, and inserted into the abdomen (part of the body that contains the digestive organs) during a laparoscopic procedure (a surgery using small incisions to introduce air and to insert a camera and other instruments in the abdominal cavity for diagnosis and/or to perform routine surgical procedures). Pressurization of the liquid chemotherapy through the study device results in aerosolization (a fine mist or spray) of the chemotherapy intra-abdominally (into the abdomen). Giving chemotherapy through PIPAC may reduce the amount of chemotherapy needed to achieve acceptable drug concentration, and therefore potentially reduces side effects and toxicities.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in 3 groups of patients: peritoneal carcinomatosis (PC) due to primary ovarian, uterine, or gastric carcinoma (Arm 1); PC due to primary colorectal or appendiceal carcinoma (Arm 2). II. To evaluate safety of PIPAC and identify the maximum tolerated dose (MTD) of PIPAC with MMC in patients with PC due to colorectal or appendiceal carcinoma (Arm 3). SECONDARY OBJECTIVES: I. Ability to proceed to cytoreduction with/without hyperthermic intraperitoneal chemotherapy (HIPEC) (Arm 3 patients). II. 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 (week 10, and 6 weeks after completing treatment; and at 18 weeks). Ib. Peritoneal regression grading score (PRGS) via biopsy at each cycle (both pre-PIPAC and post-PIPAC 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 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 3 arms. ARM I: Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin intraperitoneally (IP), followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM III: Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented informed consent of the participant and/or legally authorized representative
- •Patients must have histologically confirmed ovarian, uterine, gastric, appendiceal or colorectal cancer with PC
- •Prior IP 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 \>= 9 g/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 (Arm 1) are present or unless patients is know to have chronic liver disease (hepatitis) in which case AST and ALT must be =\< 5 x ULN
- •Alkaline phosphatase =\< 2 x ULN
Exclusion Criteria
- •Gastric and colorectal/appendiceal:
- •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/appendiceal): Known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency
- •Arm 2 (colorectal/appendiceal): Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition
- •Arm 2 (colorectal/appendiceal): Prior unanticipated severe reaction or hypersensitivity to platinum based compounds
- •Arm 2 (colorectal/appendiceal): 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
- •Arm 2 (colorectal/appendiceal): Life expectancy of less than 6 months
- •Arm 2 (colorectal/appendiceal): 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
- •Arm 2 (colorectal/appendiceal): Previous anaphylactic reaction to the chemotherapy drug used
Arms & Interventions
Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting
Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Biopsy
Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting
Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting
Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Doxorubicin
Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting
Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Intraperitoneal Chemotherapy
Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting
Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting
Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with doxorubicin IP, followed by cisplatin IP. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Questionnaire Administration
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Biopsy
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorouracil
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Intraperitoneal Chemotherapy
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Leucovorin
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Oxaliplatin
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting
Patients with colorectal or appendiceal cancer undergo PIPAC with oxaliplatin IP. 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 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Questionnaire Administration
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Biopsy
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorouracil
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Intraperitoneal Chemotherapy
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Irinotecan
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Leucovorin
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Mitomycin
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting
Patients with colorectal or appendiceal cancer who have undergo at least 4 months (or 8 cycles) of first-line standard of care chemotherapy but have not progressed on second line chemotherapy undergo PIPAC with mitomycin IP. Patients also receive standard of care irinotecan IV over 90 on day 1, leucovorin IV over 30 minutes on day 1, and fluorouracil IV on days 1-2 during weeks 2, 4, 8, 10, 14 and 16. Treatment repeats every 4-6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Questionnaire Administration
Arm IV (PIPAC, Cisplatin and nab-paclitaxel)
Patients with recurrent ovarian cancer ( platinum-resistent or platinum metastases) patients with unresectable peritoneal metastases who are not candidates for cytoreductive surgery, at least 6 months after completion of first-line standard of care chemotherapy, and no bowel obstruction. Treatment for each 28-day cycle will consist of PIPAC with cisplatin (15 mg/m2) and nab-paclitaxel (90 mg/m2) on D1 every 28 days. A dose de-escalation plan is provided if the starting dose is not well-tolerated.
Intervention: Biopsy
Arm IV (PIPAC, Cisplatin and nab-paclitaxel)
Patients with recurrent ovarian cancer ( platinum-resistent or platinum metastases) patients with unresectable peritoneal metastases who are not candidates for cytoreductive surgery, at least 6 months after completion of first-line standard of care chemotherapy, and no bowel obstruction. Treatment for each 28-day cycle will consist of PIPAC with cisplatin (15 mg/m2) and nab-paclitaxel (90 mg/m2) on D1 every 28 days. A dose de-escalation plan is provided if the starting dose is not well-tolerated.
Intervention: Cisplatin
Arm IV (PIPAC, Cisplatin and nab-paclitaxel)
Patients with recurrent ovarian cancer ( platinum-resistent or platinum metastases) patients with unresectable peritoneal metastases who are not candidates for cytoreductive surgery, at least 6 months after completion of first-line standard of care chemotherapy, and no bowel obstruction. Treatment for each 28-day cycle will consist of PIPAC with cisplatin (15 mg/m2) and nab-paclitaxel (90 mg/m2) on D1 every 28 days. A dose de-escalation plan is provided if the starting dose is not well-tolerated.
Intervention: Intraperitoneal Chemotherapy
Arm IV (PIPAC, Cisplatin and nab-paclitaxel)
Patients with recurrent ovarian cancer ( platinum-resistent or platinum metastases) patients with unresectable peritoneal metastases who are not candidates for cytoreductive surgery, at least 6 months after completion of first-line standard of care chemotherapy, and no bowel obstruction. Treatment for each 28-day cycle will consist of PIPAC with cisplatin (15 mg/m2) and nab-paclitaxel (90 mg/m2) on D1 every 28 days. A dose de-escalation plan is provided if the starting dose is not well-tolerated.
Intervention: Quality-of-Life Assessment
Arm IV (PIPAC, Cisplatin and nab-paclitaxel)
Patients with recurrent ovarian cancer ( platinum-resistent or platinum metastases) patients with unresectable peritoneal metastases who are not candidates for cytoreductive surgery, at least 6 months after completion of first-line standard of care chemotherapy, and no bowel obstruction. Treatment for each 28-day cycle will consist of PIPAC with cisplatin (15 mg/m2) and nab-paclitaxel (90 mg/m2) on D1 every 28 days. A dose de-escalation plan is provided if the starting dose is not well-tolerated.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Dose limiting toxicities
Time Frame: Up to 18 weeks
Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Summarized by type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment, and reversibility or outcome.
Incidence of adverse events
Time Frame: From day 1 of protocol therapy until week 18
Assessed using CTCAE v.5.0. Summarized by grade and attribution. Post-surgical complications will be assessed by Clavien-Dindo classification.
Secondary Outcomes
- Percentage of evaluable patients who have achieved a decrease in Peritoneal Regression Grading Score over successive biopsies(Up to 18 weeks)
- Progression-free survival(Time from first pressurized intraperitoneal aerosolized chemotherapy (PIPAC) procedure, assessed up to 1 year)
- PIPAC technical failure rate(Up to 3 years)
- Post-surgical complications(At 4 weeks after each PIPAC)
- Functional status(Up to 18 weeks)
- Cytoreductive surgery rate (Arm 3)(Up to 18 weeks)
- Percentage of evaluable patients who have achieved complete response (CR), partial response (PR), or stable disease (SD)(At baseline, following the second cycle (week 10), and 6 weeks after completing treatment (at 18 weeks/off-study))
- 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))