PIPAC for the Treatment of Peritoneal Carcinomatosis in Patients With Ovarian, Uterine, Appendiceal, Colorectal, or Gastric Cancer

Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Ovarian, Uterine, Appendiceal, Colorectal, and Gastric Cancer Patients With Peritoneal Carcinomatosis (PC)

Sponsors

Lead Sponsor: City of Hope Medical Center

Collaborator: National Cancer Institute (NCI)

Source City of Hope Medical Center
Brief Summary

This 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). Drugs used in chemotherapy, such as cisplatin, doxorubicin, oxaliplatin, leucovorin, and fluorouracil, 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 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 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, appendiceal, 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, appendiceal 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.

Overall Status Recruiting
Start Date 2020-08-21
Completion Date 2022-03-08
Primary Completion Date 2022-03-08
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Dose limiting toxicities (DLTs) Up to 18 weeks
Secondary Outcome
Measure Time Frame
Incidence of adverse events Start of treatment until week 18
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)
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)
Percentage of evaluable patients who have achieved a decrease in Peritoneal Regression Grading Score (PRGS) over successive biopsies Up to 18 weeks
Progression-free survival Time from first pressurized intraperitoneal aerosolized chemotherapy (PIPAC) procedure, assessed up to 1 year
Number of post-surgical complications At 4 weeks after each PIPAC
PIPAC technical failure rate Up to 3 years
Patient-reported health state/quality of life and symptoms Before treatment, and at 6, 12, and 18 weeks/off study
Functional status Up to 18 weeks
Enrollment 16
Condition
Intervention

Intervention Type: Drug

Intervention Name: Cisplatin

Description: Given via PIPAC

Arm Group Label: Arm I (PIPAC, cisplatin, doxorubicin)

Intervention Type: Drug

Intervention Name: Doxorubicin

Description: Given via PIPAC

Arm Group Label: Arm I (PIPAC, cisplatin, doxorubicin)

Intervention Type: Drug

Intervention Name: Fluorouracil

Description: Given IV

Arm Group Label: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)

Intervention Type: Procedure

Intervention Name: Intraperitoneal Chemotherapy

Description: Undergo PIPAC

Other Name: Intraperitoneal Therapy

Intervention Type: Drug

Intervention Name: Leucovorin

Description: Given IV

Arm Group Label: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)

Other Name: Folinic acid

Intervention Type: Drug

Intervention Name: Oxaliplatin

Description: Given via PIPAC

Arm Group Label: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)

Intervention Type: Other

Intervention Name: Quality-of-Life Assessment

Description: Ancillary studies

Other Name: Quality of Life Assessment

Intervention Type: Other

Intervention Name: Questionnaire Administration

Description: Ancillary studies

Intervention Type: Device

Intervention Name: Nebulizer with High-Pressure Injector

Description: The nebulizer turns the chemo therapy drugs into a fine mist

Eligibility

Criteria:

Inclusion Criteria: - Documented informed consent of the participant and/or legally authorized representative - Patients must have histologically confirmed ovarian, uterine, appendiceal, 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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Location
Facility: Status: Contact: Investigator:
City of Hope Medical Center | Duarte, California, 91010, United States Recruiting Thanh H. Dellinger 626-218-1379 [email protected] Thanh H. Dellinger Principal Investigator
Mayo Clinic Florida | Jacksonville, Florida, 32224, United States Recruiting Amit Merchea 904-953-2596 [email protected]
Northwell Cancer Institute | New York, New York, 10019, United States Recruiting Richard L Whelan, MD 212-434-4860 [email protected]
Location Countries

United States

Verification Date

2021-01-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm I (PIPAC, cisplatin, doxorubicin)

Type: Experimental

Description: Patients with ovarian, uterine, appendiceal, 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.

Label: Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)

Type: Experimental

Description: 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.

Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News