PIPAC Nab-pac for Stomach, Pancreas, Breast and Ovarian Cancer

NCT03304210 | Completed Phase 1 Results DMC

• 1 other identifier: AGO/2017/003
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The PIPAC nab-pac study is designed to examine the maximal tolerated dose of albumin bound nanoparticle paclitaxel (nab-pac, Abraxane) administered with repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC), in a multicentre, multinational phase I trial.

Conditions

Peritoneal Carcinomatosis; Ovarian Cancer Stage IIIB; Ovarian Cancer Stage IIIC; Ovarian Cancer Stage IV; Breast Cancer Stage IIIB; Breast Cancer Stage IIIc; Breast Cancer Stage IV; Stomach Cancer Stage III; Stomach Cancer Stage IV With Metastases; Pancreas Cancer, Stage III; Pancreas Cancer, Stage IV

Keywords

PIPAC; Peritoneal carcinomatosis; Ovarian cancer; Pharmacokinetics; Pharmacodynamics; Safety and efficacy; Abraxane; Breast cancer; Pancreas cancer; Stomach cancer

Outcome Measures

Primary Outcomes (1)

• Maximally Tolerated Dose (MTD) of Abraxane

  The MTD was defined as the highest dose of aerosolized Abraxane, administered 3 times using PIPAC, that does not cause unacceptable side effects. Dose limiting toxicity was recorded in a 14 week-window starting from the first PIPAC and defined a priori as any of the following: 1. any Grade 3 or 4 non-hematologic toxicity excluding fatigue and controllable nausea, vomiting, abdominal pain, and diarrhoea; 2. grade 4 thrombocytopenia; 3. grade 4 neutropenia lasting more than 7 days or associated with fever; 4. failure to perform more than one PIPAC due to toxicity; 5. surgical complication Dindo-Clavien grade IIIB or higher. In order to optimize the balance between safety and efficacy, we used a time-to-event continual reassessment model (TITE-CRM), where an initial design was followed until the first DLT occurred. Conservative a priori estimates of DLT were used to calculate the original dose escalation scheme.

  Within 14 weeks of the start of the treatment

Secondary Outcomes (6)

• Surgical Morbidity

  6 months after third PIPAC

• Maximum Plasma Concentration of Abraxane

  T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours

• Area Under The Curve (AUC) of Abraxane

  T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours

• Histological Response Via Peritoneal Regression Grading Scoring (PRGS)

  T = 0 minutes, before nebulization

• Neutropenia - Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC

Study Arms (5)

Abraxane 35 mg/m²

EXPERIMENTAL

PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.

Drug: PIPAC with Abraxane

Abraxane 70 mg/m²

EXPERIMENTAL

PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.

Drug: PIPAC with Abraxane

Abraxane 90 mg/m²

EXPERIMENTAL

PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.

Drug: PIPAC with Abraxane

Abraxane 112.5 mg/m²

EXPERIMENTAL

PIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.

Drug: PIPAC with Abraxane

Abraxane 140 mg/m²

EXPERIMENTAL

PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.

Drug: PIPAC with Abraxane

Interventions

PIPAC with Abraxane DRUG

Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.

Abraxane 112.5 mg/m²; Abraxane 140 mg/m²; Abraxane 35 mg/m²; Abraxane 70 mg/m²; Abraxane 90 mg/m²

Eligibility Criteria

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

You may qualify if:

• Phase I study: patients with advanced carcinomatosis from ovarian, breast, gastric, or pancreatic origin. No alternative systemic treatment options are available.
• Age over 18 years
• Adequate performance status (Karnofsky index \> 60%)
• Absence of intestinal or urinary obstruction
• Limited size of the majority of peritoneal tumor implants (\< 5 mm)
• Absent or limited ascites
• Ability to understand the proposed treatment protocol and provide informed consent
• Expected life expectancy more than 6 months
• Laboratory data
• Serum creatinine ≤ 1.5 mg/dl or a calculated GFR (CKD-EPI) ≥ 60 mL/min/1.73 m²
• Serum total bilirubin ≤ 1.5 mg/dl, except for known Gilbert's disease
• Platelet count \> 100.000/µl
• Hemoglobin \> 9g/dl
• Neutrophil granulocytes \> 1.500/ml
• No major blood coagulation disorders. Parameters within normal range.

You may not qualify if:

• Pregnancy or breast feeding. Women who can become pregnant must ensure effective contraception.
• Active bacterial, viral or fungal infection
• Active gastro-duodenal ulcer
• Parenchymal liver disease (any stage cirrhosis)
• Uncontrolled diabetes mellitus
• Psychiatric pathology affecting comprehension and judgement faculty
• General or local (abdominal) contra-indications for laparoscopic surgery
• Documented intolerance or allergy to paclitaxel
• Patients who receive other taxane therapy until three weeks before the first experimental treatment

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Kom Op Tegen Kanker: collaborator
• University Ghent: collaborator
• Hopital Lariboisière: collaborator
• University Women's Hospital Tübingen: collaborator
• Candiolo Cancer Institute - IRCCS: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (1)

UZ Ghent

Ghent, East-Flanders, 9000, Belgium

Location

Related Publications (2)

• Van De Sande L, Graversen M, Hubner M, Pocard M, Reymond M, Vaira M, Cosyns S, Willaert W, Ceelen W. Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane) for peritoneal carcinomatosis - a phase I first-in-human study. Pleura Peritoneum. 2018 Jun 8;3(2):20180112. doi: 10.1515/pp-2018-0112. eCollection 2018 Jun 1.

  PMID: 30911657 BACKGROUND

• Ceelen W, Sandra L, de Sande LV, Graversen M, Mortensen MB, Vermeulen A, Gasthuys E, Reynders D, Cosyns S, Hoorens A, Willaert W. Phase I study of intraperitoneal aerosolized nanoparticle albumin based paclitaxel (NAB-PTX) for unresectable peritoneal metastases. EBioMedicine. 2022 Aug;82:104151. doi: 10.1016/j.ebiom.2022.104151. Epub 2022 Jul 15.

  PMID: 35843174 RESULT

MeSH Terms

Conditions

Peritoneal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms

Interventions

Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Prof
• Organization: Ghent University

wim.ceelen@ugent.be

+32(0)93326251

Study Officials

• Wim P Ceelen, MD, PhD, Prof

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: October 6, 2017
• Study Start: September 16, 2017
• Primary Completion: May 6, 2020
• Study Completion: May 6, 2020
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-01

Locations

BE (1)