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

Ghent University Hospital (UZ)

Status and phase: Completed; Phase 1

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

Treatments: Drug: PIPAC with Abraxane

Study type: Interventional

Funder types: Other

Identifiers

NCT03304210

AGO/2017/003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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20 participants in 5 patient groups

Abraxane 35 mg/m²

Experimental group

Description:

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

Treatment:

Drug: PIPAC with Abraxane

Abraxane 70 mg/m²

Experimental group

Description:

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

Treatment:

Drug: PIPAC with Abraxane

Abraxane 90 mg/m²

Experimental group

Description:

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

Treatment:

Drug: PIPAC with Abraxane

Abraxane 112.5 mg/m²

Experimental group

Description:

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

Treatment:

Drug: PIPAC with Abraxane

Abraxane 140 mg/m²

Experimental group

Description:

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

Treatment:

Drug: PIPAC with Abraxane