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

NCT04329494 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 3 other identifiers: 19184NCI-2020-01254P30CA033572
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 3

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.

Conditions

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; 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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 18 weeks

• 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.

  From day 1 of protocol therapy until week 18

Secondary Outcomes (8)

• 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)

• 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

• Post-surgical complications

  At 4 weeks after each PIPAC

Study Arms (4)

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting

EXPERIMENTAL

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.

Procedure: Biopsy; Drug: Cisplatin; Drug: Doxorubicin; Device: Intraperitoneal Chemotherapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting

EXPERIMENTAL

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.

Procedure: Biopsy; Drug: Fluorouracil; Device: Intraperitoneal Chemotherapy; Drug: Leucovorin; Drug: Oxaliplatin; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting

EXPERIMENTAL

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.

Procedure: Biopsy; Drug: Fluorouracil; Device: Intraperitoneal Chemotherapy; Drug: Irinotecan; Drug: Leucovorin; Drug: Mitomycin; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm IV (PIPAC, Cisplatin and nab-paclitaxel)

EXPERIMENTAL

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.

Procedure: Biopsy; Drug: Cisplatin; Device: Intraperitoneal Chemotherapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Intraperitoneal Chemotherapy DEVICE

Undergo PIPAC

Also known as: Intraperitoneal Therapy

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting; Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting; Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting; Arm IV (PIPAC, Cisplatin and nab-paclitaxel)

Irinotecan DRUG

Given IV

Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting; Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting

Mitomycin DRUG

Given via PIPAC

Also known as: 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

Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting

Oxaliplatin DRUG

Given via PIPAC

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting; Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting; Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting; Arm IV (PIPAC, Cisplatin and nab-paclitaxel)

Questionnaire Administration OTHER

Ancillary studies

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting; Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting; Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting; Arm IV (PIPAC, Cisplatin and nab-paclitaxel)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting; Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting; Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting; Arm IV (PIPAC, Cisplatin and nab-paclitaxel)

Cisplatin DRUG

Given via PIPAC

Also known as: 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

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting; Arm IV (PIPAC, Cisplatin and nab-paclitaxel)

Doxorubicin DRUG

Given via PIPAC

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Arm I (PIPAC, doxorubicin, cisplatin) - Not recruiting

Fluorouracil DRUG

Given IV

Also known as: 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

Arm II (PIPAC, oxaliplatin, leucovorin, fluorouracil) - Not recruiting; Arm III (PIPAC, mitomycin, FOLFIRI) - Not recruiting

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Northwell Health Cancer Institute at Huntington

Greenlawn, New York, 11740, United States

RECRUITING

MeSH Terms

Conditions

Uterine Neoplasms; Appendiceal Neoplasms; Colorectal Neoplasms; Stomach Neoplasms; Neoplasm Metastasis; Ovarian Neoplasms; Peritoneal Neoplasms

Interventions

Biopsy; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Doxorubicin; Fluorouracil; dehydroftorafur; Hyperthermic Intraperitoneal Chemotherapy; Irinotecan; Leucovorin; Mitomycin; Mitozytrex; Oxaliplatin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Cecal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Cecal Diseases; Intestinal Diseases; Colonic Diseases; Rectal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Abdominal Neoplasms; Peritoneal Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Mitomycins; Indolequinones; Quinones; Azirines; Indoles; Coordination Complexes

Study Officials

• Thanh H Dellinger, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Mustafa Raoof, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: April 1, 2020
• Study Start: August 21, 2020
• Primary Completion (Estimated): January 5, 2028
• Study Completion (Estimated): January 5, 2028
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

US (3)