Safety of Intraperitoneal (IP) OXAliplatin (OXA) in Association With Systemic FOLFIRI Bevacizumab Chemotherapy in Patients With Peritoneal Carcinosis (IPOXA)

September 20, 2017 updated by: Hospices Civils de Lyon

IPOXA, Phase I/II Dose Escalation Trial Aiming to Evaluate the Safety of Intraperitoneal (IP) OXAliplatin (OXA) in Association With Systemic FOLFIRI Bevacizumab Chemotherapy in Patients With Peritoneal Carcinosis of Colorectal Origin and Uncertain Resectability.

Peritoneal carcinosis (PC) corresponds to a locoregional extension into the peritoneum of rare primary peritoneal cancers, or more frequently distant extension of digestive cancers (colorectal or gastric) or gynecological (ovarian, fallopian tube, or endometrial). PC can be considered as a distinct oncological entity as its genesis, natural history, and response to systematic treatments differ to those of other metastases. The development of PC, observed in 25-35% of colorectal cancers, is generally considered as a unfavorable event in the course of the disease. The prognosis is defined by the possibility of complete resection, possibly after neoadjuvant treatment. The benefit provided by the combination of cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) with respect to systemic chemotherapy in patients with PC of colorectal origin has been demonstrated based on overall survival in several randomized trials, among which one evaluated oxaliplatin. The evaluation of the clinical benefit-risk related to the repeated administration of non-hyperthermic intraperitoneal chemotherapy, as has been validated in ovarian cancer, in patients with PC of colorectal origin is already being investigated by several international teams.

The FOLFOXIRI + bevacizumab every 2 weeks is a modern therapeutic option in patients with this disease. The intraperitoneal rather than intravenous (IV) administration of oxaliplatin, in this combination, could increase the response of peritoneal lesions known to be relatively insensitive to IV chemotherapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

47

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clermont-Ferrand, France, 63003
      • Grenoble, France, 38700
        • Not yet recruiting
        • Service de Chirurgie Digestive et de l'Urgence, CHU Albert Michallon
        • Contact:
      • Lyon, France, 69373
        • Not yet recruiting
        • Département de Chirurgie Cancérologique, Centre Léon Bérard
        • Contact:
      • Pierre-Bénite, France, 69495
        • Recruiting
        • Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud
        • Contact:
      • Saint-Priest-en-Jarez, France, 42270
        • Not yet recruiting
        • Service Oncologie Médicale, INSTITUT DE CANCEROLOGIE DE LA LOIRE (ICL)
        • Contact:
      • Saint-Étienne, France, 42055

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ≥18 years old and ≤ 75 years old
  • ECOG Performance Status (PS) 0-2
  • Peritoneal carcinosis with locoregional extension or metastases of colorectal origin and uncertain resectability
  • PCI > 20 and / or infiltration of the hepatic pedicle and / or necessary digestive tract resections
  • Systemic chemotherapy indication, compatible with the FOLFIRI + bevacizumab combination
  • Satisfactory haematological evaluation: PNN rate greater than 1500 / mm3, platelet count greater than 100 G / l;
  • Satisfactory renal and hepatic function : serum creatinine ≤1.5 times the normal lower values or creatinine clearance ≥50 ml / min, bilirubin ≤1.25 times lower normal values, AST / ALT ≤1.5 times the lower normal values (≤5 times the lower normal values for patients with liver metastases)
  • No unstable conditions: myocardial infarction within 6 months prior to the start of the study, congestive heart failure, unstable angina, active cardiomyopathy, unstable rhythm disorder, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer or any condition that could be aggravated by treatment or limit compliance (investigator assessment);
  • No limitation in the number of previous treatments;
  • Patients may have received conventional cytotoxic chemotherapy , hormonal or immunological targeted biological agents. They should have recovered from previous grade ≤2 toxicities
  • Written informed consent
  • Known RAS status.

Exclusion Criteria:

  • Extraperitoneal metastases for which the site or number preclude potentially curative surgery at any moment during the course of the disease
  • Sign of bowel obstruction or lesions whose topography indicates a risk of intestinal perforation or inflammatory bowel disease
  • ECOG PS 3-4
  • Contraindication to the placement of a intraperitoneal central line
  • Contraindication specifically related to intraperitoneal administration of oxaliplatin
  • known history of hypersensitivity to oxaliplatin or to the excipients
  • peripheral sensory neuropathy grade ≥2
  • Pregnant or lactating women
  • Unable to give consent
  • Patient under legal protection measures
  • Refusal to participate in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with peritoneal carcinosis
Patients with peritoneal carcinosis of colorectal origin and uncertain resectability with an indication for systemic chemotherapy compatible with the FOLFIRI + bevacizumab combination.
Drug: intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy
Intraperitoneal (IP) OXAliplatin (OXA) in association with systemic FOLFIRI bevacizumab chemotherapy Intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI (Irinotecan IV + 5-FU IV) bevacizumab chemotherapy in escalation dose (every 14 days) starting with the level 1
Drug: intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy
systemic FOLFIRI chemotherapy
Drug: intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy
bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events (NCI CTCAE v4.0)
Time Frame: up to 14 days
The safety of intraperitoneal (IP) administration of oxaliplatin in combination with systemic chemotherapy FOLFIRI + bevacizumab will be evaluated during the first cycle of therapy according to NCI CTCAE version 4.0
up to 14 days
Dose Limiting Toxicities, DLT
Time Frame: up to 14 days
The safety of intraperitoneal (IP) administration of oxaliplatin in combination with systemic chemotherapy FOLFIRI + bevacizumab will be evaluated during the first cycle of therapy according to Dose Limiting Toxicities
up to 14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate according to RECIST
Time Frame: up to 4 months
Clinical efficacy of intraperitoneal (IP) administration of oxaliplatin in combination with systemic FOLFIRI + bevacizumab assessed by the overall response rate according to RECIST version 1.1 criteria assessed by imaging (TAP scanner and / or MRI if contraindication) performed after 4 cycles, and / or after 8 cycles
up to 4 months
Peritoneal Cancer Index (PCI)
Time Frame: up to 4 months
Clinical efficacy of intraperitoneal (IP) administration of oxaliplatin in combination with systemic FOLFIRI + bevacizumab assessed by Peritoneal Cancer Index (PCI) performed after 4 cycles, and / or after 8 cycles
up to 4 months
Adverse events (NCI CTCAE v4.0)
Time Frame: up to 5 months
The safety of intraperitoneal (IP) administration of oxaliplatin in combination with systemic chemotherapy FOLFIRI + bevacizumab will be evaluated throughout the duration of treatment (4 months) and until the end of patient follow up (1 month after treatment discontinuation) according to NCI CTCAE version 4.0
up to 5 months
The quality of life (EORTC QLQ-C30)
Time Frame: up to 4 months
The quality of life will be evaluated throughout the duration of treatment (4 months max) after the end of cycle 2, 4, 6 and 8 of chemotherapy according to EORTC QLQ-C30 .
up to 4 months
The quality of life (EORTC QLQ-C29)
Time Frame: up to 4 months
The quality of life will be evaluated throughout the duration of treatment (4 months max) after the end of cycle 2, 4, 6 and 8 of chemotherapy according to EORTC QLQ-C29.
up to 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Benoit You, MD, Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud 69495 Pierre-Bénite

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2017

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

March 1, 2019

Study Registration Dates

First Submitted

August 4, 2016

First Submitted That Met QC Criteria

August 10, 2016

First Posted (Estimate)

August 15, 2016

Study Record Updates

Last Update Posted (Actual)

September 21, 2017

Last Update Submitted That Met QC Criteria

September 20, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL16_0134

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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