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

Primary Purpose

Peritoneal Carcinomatosis, Ovarian Cancer Stage IIIB, Ovarian Cancer Stage IIIC

Status

Completed

Phase

Phase 1

Locations

Belgium

Study Type

Interventional

Intervention

PIPAC with Abraxane

About this trial

This is an interventional treatment trial for Peritoneal Carcinomatosis focused on measuring PIPAC, Peritoneal carcinomatosis, Ovarian cancer, Pharmacokinetics, Pharmacodynamics, Safety and efficacy, Abraxane, Breast cancer, Pancreas cancer, Stomach cancer

Eligibility Criteria

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

Sites / Locations

UZ Ghent

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Abraxane 35 mg/m²

Abraxane 70 mg/m²

Abraxane 90 mg/m²

Abraxane 112.5 mg/m²

Abraxane 140 mg/m²

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

Maximally tolerated dose (MTD) of Abraxane

Dose limiting toxicities will be monitored.

Secondary Outcome Measures

Surgical morbidity will be measured

This will be estimated with the Dindo-Clavien classification

Maximum plasma concentration of Abraxane

Abraxane will be measured in plasma, using UPLC-MS/MS.

Area Under The Curve (AUC) of Abraxane

Abraxane will be measured in plasma, using LC-MS/MS.

Pharmacodynamics (PD) of Abraxane will be analysed using biomarkers

Tumour markers will be analysed - CA15.3 in case of breast cancer, CEA in case of stomach cancer, CA19.9 in case of pancreatic cancer, CA125 in case of ovarian cancer.

Pharmacodynamics (PD) of Abraxane will be analyzed by tumour biopsies

Tumour samples will be collected (5x5x5 mm³) at the end of the aerosol delivery after each PIPAC procedure.

Quality of Life (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30)

This will be investigated using the EORTC QLQ-C30 questionnaire. As to question 1 to 28: the scale varies from 1 (not at all) to 4 (very much). A higher value indicates a lower quality of life. The total score will be between 28 and 112. The scale of question 29 and 30 varies from 1 (very poor) to 7 (excellent). The higher the value, the better the quality of life. The total score will be between 2 and 14.

Quality of Life (Functional Assessment of Cancer Therapy, FACT-G questionnaire)

This will be investigated using the FACT-G questionnaire. The scale of all questions varies from 0 (not at all) to 4 (very much). The total score will be between 0 and 108. The lower the total score, the better the quality of life.

Neutropenia - number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Blood samples will be collected to analyse the absolute neutrophil count

Decreased platelets - number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Blood samples will be collected to analyse the amount of platelets.

Full Information

NCT ID

NCT03304210

First Posted

September 11, 2017

Last Updated

August 3, 2020

Sponsor

University Hospital, Ghent

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03304210

Brief Title

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

Acronym

PIPAC-nabpac

Official Title

Intraperitoneal Aerosolization of Albumin-stabilized Paclitaxel Nanoparticles for Stomach, Pancreas, Breast and Ovarian Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

September 16, 2017 (Actual)

Primary Completion Date

May 6, 2020 (Actual)

Study Completion Date

May 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Ghent

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Abraxane 35 mg/m²

Arm Type

Experimental

Arm Description

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

Arm Title

Abraxane 70 mg/m²

Arm Type

Experimental

Arm Description

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

Arm Title

Abraxane 90 mg/m²

Arm Type

Experimental

Arm Description

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

Arm Title

Abraxane 112.5 mg/m²

Arm Type

Experimental

Arm Description

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

Arm Title

Abraxane 140 mg/m²

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

PIPAC with Abraxane

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximally tolerated dose (MTD) of Abraxane

Description

Dose limiting toxicities will be monitored.

Time Frame

Within 14 weeks of the start of the treatment

Secondary Outcome Measure Information:

Title

Surgical morbidity will be measured

Description

This will be estimated with the Dindo-Clavien classification

Time Frame

6 months after third PIPAC

Title

Maximum plasma concentration of Abraxane

Description

Abraxane will be measured in plasma, using UPLC-MS/MS.

Time Frame

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

Title

Area Under The Curve (AUC) of Abraxane

Description

Abraxane will be measured in plasma, using LC-MS/MS.

Time Frame

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

Title

Pharmacodynamics (PD) of Abraxane will be analysed using biomarkers

Description

Tumour markers will be analysed - CA15.3 in case of breast cancer, CEA in case of stomach cancer, CA19.9 in case of pancreatic cancer, CA125 in case of ovarian cancer.

Time Frame

T = 0 weeks, T = 1 week for every PIPAC

Title

Pharmacodynamics (PD) of Abraxane will be analyzed by tumour biopsies

Description

Tumour samples will be collected (5x5x5 mm³) at the end of the aerosol delivery after each PIPAC procedure.

Time Frame

T = 30 minutes

Title

Quality of Life (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30)

Description

Time Frame

Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC)

Title

Quality of Life (Functional Assessment of Cancer Therapy, FACT-G questionnaire)

Description

Time Frame

Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC)

Title

Neutropenia - number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Description

Blood samples will be collected to analyse the absolute neutrophil count

Time Frame

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

Title

Decreased platelets - number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Description

Blood samples will be collected to analyse the amount of platelets.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wim P Ceelen, MD, PhD, Prof

Organizational Affiliation

University Hospital, Ghent

Official's Role

Principal Investigator

Facility Information:

Facility Name

UZ Ghent

City

Ghent

State/Province

East-Flanders

ZIP/Postal Code

9000

Country

Belgium

12. IPD Sharing Statement

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Citation

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

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