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

NCT ID: NCT03304210

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-16
• Study Completion Date: 2020-05-06

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.

Detailed Description

Over 85% of women with ovarian cancer (OC) will develop a peritoneal recurrence after initial therapy. The prognosis of patients with recurrent disease is poor, with a median survival ranging from 12 to 24 months. Most of these patients ultimately develop platinum resistant disease (PROC). Current systemic therapy results in a very modest improvement of progression free and overall survival. The addition of locoregional, intraperitoneal (IP) therapy may improve disease control in recurrent OC. Recently, pressurized intraperitoneal aerosol therapy (PIPAC) was added to the therapeutic arsenal. This novel technique allows repeated laparoscopy aided aerosol delivery of anticancer drugs to the peritoneal cavity. Abraxane (nab-pac, Celgene) is a novel 130 nm, albumin-bound (nab) nanoparticle formulation of paclitaxel which has noteworthy single-agent activity and a favourable toxicity profile when used systemically in PROC. A recent phase I study showed a significant pharmacokinetic advantage after IP instillation of nab-pac in patients with peritoneal carcinomatosis from ovarian or gastro-intestinal (GI) origin.

In phase I of this study, dose escalation will be combined with pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Abraxane 35 mg/m²

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

Group Type: EXPERIMENTAL

PIPAC with Abraxane

Intervention Type: 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 70 mg/m²

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

Group Type: EXPERIMENTAL

PIPAC with Abraxane

Intervention Type: 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 90 mg/m²

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

Group Type: EXPERIMENTAL

PIPAC with Abraxane

Intervention Type: 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

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

Group Type: EXPERIMENTAL

PIPAC with Abraxane

Intervention Type: 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 140 mg/m²

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

Group Type: EXPERIMENTAL

PIPAC with Abraxane

Intervention Type: 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.

Interventions

PIPAC with Abraxane

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• Absence of alcohol and/or drug abuse
• No other concurrent malignant disease
• Written informed consent

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kom Op Tegen Kanker

OTHER

Sponsor Role: collaborator

University Ghent

OTHER

Sponsor Role: collaborator

Hopital Lariboisière

OTHER

Sponsor Role: collaborator

University Women's Hospital Tübingen

OTHER

Sponsor Role: collaborator

Candiolo Cancer Institute - IRCCS

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire Vaudois

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wim P Ceelen, MD, PhD, Prof

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

UZ Ghent

Ghent, East-Flanders, Belgium

Countries

Belgium

References

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.

Reference Type: BACKGROUND

PMID: 30911657 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35843174 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AGO/2017/003

Identifier Type: -

Identifier Source: org_study_id