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

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ClinicalTrials.gov Identifier: NCT03304210
Recruitment Status : Recruiting
First Posted : October 6, 2017
Last Update Posted : June 4, 2018
Sponsor:
Collaborators:
Kom Op Tegen Kanker
University Ghent
Hopital Lariboisière
University Women's Hospital Tübingen
Candiolo Cancer Institute - IRCCS
Centre Hospitalier Universitaire Vaudois
Information provided by (Responsible Party):
University Hospital, Ghent

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.

Condition or disease Intervention/treatment Phase
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 Drug: PIPAC with Abraxane Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intraperitoneal Aerosolization of Albumin-stabilized Paclitaxel Nanoparticles for Stomach, Pancreas, Breast and Ovarian Cancer
Actual Study Start Date : October 25, 2017
Estimated Primary Completion Date : September 21, 2020
Estimated Study Completion Date : December 21, 2020


Arm Intervention/treatment
Experimental: Abraxane 35 mg/m²
PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.
Drug: 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.

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

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

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

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




Primary Outcome Measures :
  1. Maximally tolerated dose (MTD) of Abraxane [ Time Frame: Within 14 weeks of the start of the treatment ]
    Dose limiting toxicities will be monitored.


Secondary Outcome Measures :
  1. Surgical morbidity will be measured [ Time Frame: 6 months after third PIPAC ]
    This will be estimated with the Dindo-Clavien classification

  2. Maximum plasma concentration of Abraxane [ 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 ]
    Abraxane will be measured in plasma, using UPLC-MS/MS.

  3. Area Under The Curve (AUC) of Abraxane [ 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 ]
    Abraxane will be measured in plasma, using LC-MS/MS.

  4. Pharmacodynamics (PD) of Abraxane will be analysed using biomarkers [ Time Frame: T = 0 weeks, T = 1 week for every PIPAC ]
    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.

  5. Pharmacodynamics (PD) of Abraxane will be analyzed by tumour biopsies [ Time Frame: T = 30 minutes ]
    Tumour samples will be collected (5x5x5 mm³) at the end of the aerosol delivery after each PIPAC procedure.

  6. Quality of Life (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30) [ Time Frame: Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC) ]

    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.


  7. Quality of Life (Functional Assessment of Cancer Therapy, FACT-G questionnaire) [ Time Frame: Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC) ]
    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.

  8. Neutropenia - number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC ]
    Blood samples will be collected to analyse the absolute neutrophil count

  9. Decreased platelets - number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC ]
    Blood samples will be collected to analyse the amount of platelets.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03304210


Contacts
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Contact: Wim P Ceelen, MD, PhD, Prof +3293326251 wim.ceelen@ugent.be
Contact: Leen Van de Sande, MSc +3293321564 leen.vandesande@ugent.be

Locations
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Belgium
UZ Ghent Recruiting
Ghent, East-Flanders, Belgium, 9000
Contact: Wim P Ceelen, MD, PhD, Prof    +3293326251    wim.ceelen@ugent.be   
Contact: Wouter Willaert, MD, PhD    +3293328950    wouter.willaert@ugent.be   
Sponsors and Collaborators
University Hospital, Ghent
Kom Op Tegen Kanker
University Ghent
Hopital Lariboisière
University Women's Hospital Tübingen
Candiolo Cancer Institute - IRCCS
Centre Hospitalier Universitaire Vaudois
Investigators
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Principal Investigator: Wim P Ceelen, MD, PhD, Prof University Hospital, Ghent

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT03304210     History of Changes
Other Study ID Numbers: AGO/2017/003
First Posted: October 6, 2017    Key Record Dates
Last Update Posted: June 4, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Ghent:
PIPAC
Peritoneal carcinomatosis
Ovarian cancer
Pharmacokinetics
Pharmacodynamics
Safety and efficacy
Abraxane
Breast cancer
Pancreas cancer
Stomach cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma
Pancreatic Neoplasms
Peritoneal Neoplasms
Stomach Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Digestive System Diseases
Pancreatic Diseases
Abdominal Neoplasms
Peritoneal Diseases
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel