PIPAC for the Treatment of Peritoneal Carcinomatosis in Patients With Ovarian, Uterine, Appendiceal, Colorectal, or Gastric Cancer
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| ClinicalTrials.gov Identifier: NCT04329494 |
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Recruitment Status :
Recruiting
First Posted : April 1, 2020
Last Update Posted : January 11, 2021
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Sponsor:
City of Hope Medical Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Clinical Stage IV Gastric Cancer AJCC v8 Clinical Stage IVA Gastric Cancer AJCC v8 Clinical Stage IVB Gastric Cancer AJCC v8 Malignant Uterine Neoplasm Metastatic Colorectal Carcinoma Metastatic Gastric Carcinoma Metastatic Malignant Neoplasm in the Peritoneum Metastatic Ovarian Carcinoma Pathologic Stage IV Gastric Cancer AJCC v8 Peritoneal Carcinomatosis Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8 Stage IV Colorectal Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IV Uterine Corpus Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVA Uterine Corpus Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8 Stage IVB Uterine Corpus Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Stage IIIA Ovarian Cancer Stage IIIB Ovarian Cancer Stage IIIC Ovarian Cancer Stage IIIA Endometrial Cancer Stage IIIB Endometrial Cancer Stage IIIC Endometrial Cancer Appendiceal Cancer | Drug: Cisplatin Drug: Doxorubicin Drug: Fluorouracil Procedure: Intraperitoneal Chemotherapy Drug: Leucovorin Drug: Oxaliplatin Other: Quality-of-Life Assessment Other: Questionnaire Administration Device: Nebulizer with High-Pressure Injector | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 16 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Ovarian, Uterine, Appendiceal, Colorectal, and Gastric Cancer Patients With Peritoneal Carcinomatosis (PC) |
| Actual Study Start Date : | August 21, 2020 |
| Estimated Primary Completion Date : | March 8, 2022 |
| Estimated Study Completion Date : | March 8, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
MedlinePlus related topics:
Stomach Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (PIPAC, cisplatin, doxorubicin)
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.
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Drug: Cisplatin
Given via PIPAC
Other Names:
Drug: Doxorubicin Given via PIPAC
Other Names:
Procedure: Intraperitoneal Chemotherapy Undergo PIPAC
Other Name: Intraperitoneal Therapy Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Device: Nebulizer with High-Pressure Injector The nebulizer turns the chemo therapy drugs into a fine mist |
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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.
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Drug: Fluorouracil
Given IV
Other Names:
Procedure: Intraperitoneal Chemotherapy Undergo PIPAC
Other Name: Intraperitoneal Therapy Drug: Leucovorin Given IV
Other Name: Folinic acid Drug: Oxaliplatin Given via PIPAC
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Device: Nebulizer with High-Pressure Injector The nebulizer turns the chemo therapy drugs into a fine mist |
Primary Outcome Measures :
- Dose limiting toxicities (DLTs) [ Time Frame: Up to 18 weeks ]Assessed by Common Terminology Criteria for Adverse Events version 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.
Secondary Outcome Measures :
- Incidence of adverse events [ Time Frame: Start of treatment until week 18 ]Summarized by grade (CTCAE v.5.0) and attribution.
- Percentage of evaluable patients who have achieved complete response (CR), partial response (PR), or stable disease (SD) [ Time Frame: At baseline, week 10, and 6 weeks after completing treatment (at 18 weeks/off-study) ]Assessed by Response Evaluation Criteria in Solid Tumors criteria version 1.1 via computed tomography (CT) scan. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach by Clopper and Pearson.
- Percentage of evaluable patients who have achieved CR, PR, or SD [ Time Frame: At the time of laparoscopy (or CT imaging if laparoscopy is not planned during surgery) ]Assessed by Peritoneal Carcinomatosis Index. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach by Clopper and Pearson.
- Percentage of evaluable patients who have achieved a decrease in Peritoneal Regression Grading Score (PRGS) over successive biopsies [ Time Frame: Up to 18 weeks ]The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach by Clopper and Pearson.
- Progression-free survival [ Time Frame: Time from first pressurized intraperitoneal aerosolized chemotherapy (PIPAC) procedure, assessed up to 1 year ]Described using the Kaplan-Meier method.
- Number of post-surgical complications [ Time Frame: At 4 weeks after each PIPAC ]Adverse events by grade according to Clavien-Dindo classification.
- PIPAC technical failure rate [ Time Frame: Up to 3 years ]
- Patient-reported health state/quality of life and symptoms [ Time Frame: Before treatment, and at 6, 12, and 18 weeks/off study ]Measured by European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L) and MD Anderson Symptom Inventory (MDASI).
- Functional status [ Time Frame: Up to 18 weeks ]Measured by the number of daily steps before and after treatments (Vivofit 4 wristband pedometer - Garmin Company).
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
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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:
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Gastric and colorectal:
- Extra-peritoneal metastatic disease
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Arm 1 (ovarian, uterine, gastric):
- Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04329494
Locations
| United States, California | |
| City of Hope Medical Center | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: Thanh H. Dellinger 626-218-1379 tdellinger@coh.org | |
| Principal Investigator: Thanh H. Dellinger | |
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Thanh H Dellinger | City of Hope Medical Center | |
| Principal Investigator: | Mustafa Raoof, MD | City of Hope Medical Center |
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT04329494 |
| Other Study ID Numbers: |
19184 NCI-2020-01254 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 19184 ( Other Identifier: City of Hope Medical Center ) |
| First Posted: | April 1, 2020 Key Record Dates |
| Last Update Posted: | January 11, 2021 |
| Last Verified: | January 2021 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | Yes |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Carcinoma Neoplasms Colorectal Neoplasms Ovarian Neoplasms Carcinoma, Ovarian Epithelial Stomach Neoplasms Endometrial Neoplasms Peritoneal Neoplasms Uterine Neoplasms Appendiceal Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms |
Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Endocrine Gland Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Stomach Diseases Uterine Diseases |