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

Primary Purpose

Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IVA Gastric Cancer AJCC v8, Clinical Stage IVB Gastric Cancer AJCC v8

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Biopsy
Cisplatin
Doxorubicin
Fluorouracil
Intraperitoneal Chemotherapy
Irinotecan
Leucovorin
Mitomycin
Oxaliplatin
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clinical Stage IV Gastric Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • 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 does 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 (Arm 1 and 2). For Arm 3, patients should have stable or responsive disease on at least 4 months first-line systemic chemotherapy
  • 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 another 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 (vaginal 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 HIPEC

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
  • Arm 2 (colorectal/appendiceal): Patients may not be receiving any other investigational or concurrent anti-cancer agents
  • Arm 2 (colorectal/appendiceal): Ascites due to decompensated liver cirrhosis; portal vein thrombosis
  • Arm 2 (colorectal/appendiceal): Simultaneous tumor debulking with gastrointestinal resection
  • Arm 2 (colorectal/appendiceal): 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
  • Arm 2 (colorectal/appendiceal): Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system
  • Arm 2 (colorectal/appendiceal): Involvement in the planning and conduct of the study
  • Arm 2 (colorectal/appendiceal): Pregnancy
  • Arm 2 (colorectal/appendiceal): Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Arm 2 (colorectal/appendiceal): 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
  • Arm 2 (colorectal/appendiceal): Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug
  • Arm 2 (colorectal/appendiceal): Exclusive total parenteral nutrition
  • Arm 2 (colorectal/appendiceal): Prior intra-abdominal aerosol chemotherapy
  • Arm 3 (colorectal/appendiceal): Progression on first- AND second-line systemic therapy
  • Arm 3 (colorectal/appendiceal): Hematologic toxicities requiring significant dose reductions while on systemic chemotherapy
  • Arm 3 (colorectal/appendiceal): Intolerance to prior 5-FU at 2400mg/m^2 IV every 2 weeks or to irinotecan at 180mg/m^2. Intolerance is defined as the need of significant dose reduction or treatment interruption of > 1 week due to toxicity
  • Arm 3 (colorectal/appendiceal): Known DPD deficiency
  • Arm 3 (colorectal/appendiceal): Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition
  • Arm 3 (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 3 (colorectal/appendiceal): Life expectancy of less than 6 months
  • Arm 3 (colorectal/appendiceal): Chemotherapy or surgery within the last 2 weeks prior to enrollment (6 weeks for prior bevacizumab therapy). Five half-lives for other anti-cancer agents
  • Arm 3 (colorectal/appendiceal): Previous anaphylactic reaction to the chemotherapy drug used
  • Arm 3 (colorectal/appendiceal): Patients may not be receiving any other investigational anti-cancer agents
  • Arm 3 (colorectal/appendiceal): Ascites due to decompensated liver cirrhosis; portal vein thrombosis
  • Arm 3 (colorectal/appendiceal): Simultaneous tumor debulking with gastrointestinal resection
  • Arm 3 (colorectal/appendiceal): 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
  • Arm 3 (colorectal/appendiceal): Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system
  • Arm 3 (colorectal/appendiceal): Involvement in the planning and conduct of the study
  • Arm 3 (colorectal/appendiceal): Pregnancy
  • Arm 3 (colorectal/appendiceal): Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Arm 3 (colorectal/appendiceal): 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
  • Arm 3 (colorectal/appendiceal): Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug
  • Arm 3 (colorectal/appendiceal): Exclusive total parenteral nutrition
  • Arm 3 (colorectal/appendiceal): Prior intra-abdominal aerosol chemotherapy

Sites / Locations

  • City of Hope Medical CenterRecruiting
  • Mayo Clinic in FloridaRecruiting
  • Northwell Health Cancer Institute at HuntingtonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm I (PIPAC, doxorubicin, cisplatin)

Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)

Arm III (PIPAC, mitomycin, FOLFIRI)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Dose limiting toxicities
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
Assessed using CTCAE v.5.0. Summarized by grade and attribution. Post-surgical complications will be assessed by Clavien-Dindo classification.

Secondary Outcome Measures

Percentage of evaluable patients who have achieved complete response (CR), partial response (PR), or stable disease (SD)
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
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 over successive biopsies
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
Described using the Kaplan-Meier method.
Post-surgical complications
Assessed by Clavien-Dindo classification. Results will be strictly descriptive in nature.
PIPAC technical failure rate
Functional status
Measured by the number of daily steps before and after treatments (Vivofit 4 wristband pedometer - Garmin Company).
Cytoreductive surgery rate (Arm 3)

Full Information

First Posted
March 13, 2020
Last Updated
September 11, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04329494
Brief Title
PIPAC for the Treatment of Peritoneal Carcinomatosis in Patients With Ovarian, Uterine, Appendiceal, Colorectal, or Gastric Cancer
Official Title
Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Ovarian, Uterine, Appendiceal, Colorectal, and Gastric Cancer Patients With Peritoneal Carcinomatosis (PC)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 21, 2020 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Appendix Carcinoma, Metastatic Colorectal Carcinoma, Metastatic Gastric Carcinoma, Metastatic Malignant Neoplasm in the Peritoneum, Metastatic Malignant Solid Neoplasm, Metastatic Ovarian Carcinoma, Pathologic Stage IV Gastric Cancer AJCC v8, Peritoneal Carcinomatosis, Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8, Stage IV Appendix Carcinoma AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Uterine Corpus Cancer AJCC v8, Stage IVA Appendix Carcinoma AJCC v8, Stage IVA Colorectal Cancer AJCC v8, Stage IVA Ovarian Cancer AJCC v8, Stage IVA Uterine Corpus Cancer AJCC v8, Stage IVB Appendix Carcinoma AJCC v8, Stage IVB Colorectal Cancer AJCC v8, Stage IVB Ovarian Cancer AJCC v8, Stage IVB Uterine Corpus Cancer AJCC v8, Stage IVC Appendix Carcinoma AJCC v8, Stage IVC Colorectal Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (PIPAC, doxorubicin, cisplatin)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm III (PIPAC, mitomycin, FOLFIRI)
Arm Type
Experimental
Arm Description
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 Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo biopsy
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Intervention Description
Given via PIPAC
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Intervention Description
Given via PIPAC
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757
Intervention Description
Given IV
Intervention Type
Device
Intervention Name(s)
Intraperitoneal Chemotherapy
Other Intervention Name(s)
Intraperitoneal Therapy
Intervention Description
Undergo PIPAC
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Mitomycin
Other Intervention Name(s)
Ametycine, Jelmyto, MITO, Mito-C, Mito-Medac, Mitocin, Mitocin-C, Mitolem, Mitomycin C, Mitomycin-C, Mitomycin-X, Mitomycine C, Mitosol, Mitozytrex, Mutamycin, Mutamycine, NCI-C04706
Intervention Description
Given via PIPAC
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669
Intervention Description
Given via PIPAC
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Dose limiting toxicities
Description
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.
Time Frame
Up to 18 weeks
Title
Incidence of adverse events
Description
Assessed using CTCAE v.5.0. Summarized by grade and attribution. Post-surgical complications will be assessed by Clavien-Dindo classification.
Time Frame
From day 1 of protocol therapy until week 18
Secondary Outcome Measure Information:
Title
Percentage of evaluable patients who have achieved complete response (CR), partial response (PR), or stable disease (SD)
Description
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.
Time Frame
At baseline, following the second cycle (week 10), and 6 weeks after completing treatment (at 18 weeks/off-study)
Title
Percentage of evaluable patients who have achieved CR, PR, or SD
Description
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.
Time Frame
At the time of laparoscopy (or CT imaging if laparoscopy is not planned during surgery)
Title
Percentage of evaluable patients who have achieved a decrease in Peritoneal Regression Grading Score over successive biopsies
Description
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.
Time Frame
Up to 18 weeks
Title
Progression-free survival
Description
Described using the Kaplan-Meier method.
Time Frame
Time from first pressurized intraperitoneal aerosolized chemotherapy (PIPAC) procedure, assessed up to 1 year
Title
Post-surgical complications
Description
Assessed by Clavien-Dindo classification. Results will be strictly descriptive in nature.
Time Frame
At 4 weeks after each PIPAC
Title
PIPAC technical failure rate
Time Frame
Up to 3 years
Title
Functional status
Description
Measured by the number of daily steps before and after treatments (Vivofit 4 wristband pedometer - Garmin Company).
Time Frame
Up to 18 weeks
Title
Cytoreductive surgery rate (Arm 3)
Time Frame
Up to 18 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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 does 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 (Arm 1 and 2). For Arm 3, patients should have stable or responsive disease on at least 4 months first-line systemic chemotherapy 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 another 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 (vaginal 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 HIPEC 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 Arm 2 (colorectal/appendiceal): Patients may not be receiving any other investigational or concurrent anti-cancer agents Arm 2 (colorectal/appendiceal): Ascites due to decompensated liver cirrhosis; portal vein thrombosis Arm 2 (colorectal/appendiceal): Simultaneous tumor debulking with gastrointestinal resection Arm 2 (colorectal/appendiceal): 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 Arm 2 (colorectal/appendiceal): Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system Arm 2 (colorectal/appendiceal): Involvement in the planning and conduct of the study Arm 2 (colorectal/appendiceal): Pregnancy Arm 2 (colorectal/appendiceal): Patients with psychiatric illness/social situations that would limit compliance with study requirements Arm 2 (colorectal/appendiceal): 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 Arm 2 (colorectal/appendiceal): Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug Arm 2 (colorectal/appendiceal): Exclusive total parenteral nutrition Arm 2 (colorectal/appendiceal): Prior intra-abdominal aerosol chemotherapy Arm 3 (colorectal/appendiceal): Progression on first- AND second-line systemic therapy Arm 3 (colorectal/appendiceal): Hematologic toxicities requiring significant dose reductions while on systemic chemotherapy Arm 3 (colorectal/appendiceal): Intolerance to prior 5-FU at 2400mg/m^2 IV every 2 weeks or to irinotecan at 180mg/m^2. Intolerance is defined as the need of significant dose reduction or treatment interruption of > 1 week due to toxicity Arm 3 (colorectal/appendiceal): Known DPD deficiency Arm 3 (colorectal/appendiceal): Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition Arm 3 (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 3 (colorectal/appendiceal): Life expectancy of less than 6 months Arm 3 (colorectal/appendiceal): Chemotherapy or surgery within the last 2 weeks prior to enrollment (6 weeks for prior bevacizumab therapy). Five half-lives for other anti-cancer agents Arm 3 (colorectal/appendiceal): Previous anaphylactic reaction to the chemotherapy drug used Arm 3 (colorectal/appendiceal): Patients may not be receiving any other investigational anti-cancer agents Arm 3 (colorectal/appendiceal): Ascites due to decompensated liver cirrhosis; portal vein thrombosis Arm 3 (colorectal/appendiceal): Simultaneous tumor debulking with gastrointestinal resection Arm 3 (colorectal/appendiceal): 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 Arm 3 (colorectal/appendiceal): Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system Arm 3 (colorectal/appendiceal): Involvement in the planning and conduct of the study Arm 3 (colorectal/appendiceal): Pregnancy Arm 3 (colorectal/appendiceal): Patients with psychiatric illness/social situations that would limit compliance with study requirements Arm 3 (colorectal/appendiceal): 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 Arm 3 (colorectal/appendiceal): Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug Arm 3 (colorectal/appendiceal): Exclusive total parenteral nutrition Arm 3 (colorectal/appendiceal): Prior intra-abdominal aerosol chemotherapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thanh H Dellinger, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mustafa Raoof, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thanh H. Dellinger
Phone
626-218-1379
Email
tdellinger@coh.org
First Name & Middle Initial & Last Name & Degree
Thanh H. Dellinger
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amit L. Merchea
Phone
904-953-2596
Email
Merchea.AmitL@mayo.edu
First Name & Middle Initial & Last Name & Degree
Amit L. Merchea
Facility Name
Northwell Health Cancer Institute at Huntington
City
Greenlawn
State/Province
New York
ZIP/Postal Code
11740
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard L. Whelan
Phone
212-434-4860
Email
rwhelan1@northwell.edu
First Name & Middle Initial & Last Name & Degree
Richard L. Whelan

12. IPD Sharing Statement

Learn more about this trial

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

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