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

Primary Purpose

Peritoneal Carcinosis

Status

Unknown status

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy

About this trial

This is an interventional treatment trial for Peritoneal Carcinosis focused on measuring Peritoneal carcinosis, intraperitoneal (IP) OXAliplatin, Phase I/II dose escalation trial, FOLFIRI Bevacizumab chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

CHU Estaing
Service de Chirurgie Digestive et de l'Urgence, CHU Albert Michallon
Département de Chirurgie Cancérologique, Centre Léon Bérard
Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon SudRecruiting
Service Oncologie Médicale, INSTITUT DE CANCEROLOGIE DE LA LOIRE (ICL)
Service de Chirurgie Digestive et Cancérologique, CHU NORD

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with peritoneal carcinosis

Arm Description

Patients with peritoneal carcinosis of colorectal origin and uncertain resectability with an indication for systemic chemotherapy compatible with the FOLFIRI + bevacizumab combination.

Outcomes

Primary Outcome Measures

Adverse events (NCI CTCAE v4.0)

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

Dose Limiting Toxicities, DLT

Secondary Outcome Measures

Overall response rate according to RECIST

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

Peritoneal Cancer Index (PCI)

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

Adverse events (NCI CTCAE v4.0)

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

The quality of life (EORTC QLQ-C30)

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 .

The quality of life (EORTC QLQ-C29)

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.

Full Information

NCT ID

NCT02866903

First Posted

August 4, 2016

Last Updated

September 20, 2017

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT02866903

Brief Title

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

Acronym

IPOXA

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Unknown status

Study Start Date

May 18, 2017 (Actual)

Primary Completion Date

March 2019 (Anticipated)

Study Completion Date

March 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

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

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.

6. Conditions and Keywords

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

Peritoneal Carcinosis

Keywords

Peritoneal carcinosis, intraperitoneal (IP) OXAliplatin, Phase I/II dose escalation trial, FOLFIRI Bevacizumab chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

47 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Patients with peritoneal carcinosis

Arm Type

Experimental

Arm Description

Patients with peritoneal carcinosis of colorectal origin and uncertain resectability with an indication for systemic chemotherapy compatible with the FOLFIRI + bevacizumab combination.

Intervention Type

Drug

Intervention Name(s)

intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy

Intervention Description

systemic FOLFIRI chemotherapy

Intervention Type

Drug

Intervention Name(s)

intraperitoneal (IP) OXAliplatin (OXA) + systemic FOLFIRI bevacizumab chemotherapy

Intervention Description

bevacizumab

Primary Outcome Measure Information:

Title

Adverse events (NCI CTCAE v4.0)

Description

Time Frame

up to 14 days

Title

Dose Limiting Toxicities, DLT

Description

Time Frame

up to 14 days

Secondary Outcome Measure Information:

Title

Overall response rate according to RECIST

Description

Time Frame

up to 4 months

Title

Peritoneal Cancer Index (PCI)

Description

Time Frame

up to 4 months

Title

Adverse events (NCI CTCAE v4.0)

Description

Time Frame

up to 5 months

Title

The quality of life (EORTC QLQ-C30)

Description

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 .

Time Frame

up to 4 months

Title

The quality of life (EORTC QLQ-C29)

Description

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.

Time Frame

up to 4 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Benoit You, MD

Phone

(0)4 78 86 43 18

Ext

+33

benoit.you@chu-lyon.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benoit You, MD

Organizational Affiliation

Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud 69495 Pierre-Bénite

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU Estaing

City

Clermont-Ferrand

ZIP/Postal Code

63003

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Denis Pr PEZET

Phone

(0)4 73 75 04 94

Ext

+33

dpezet@chu-clermontferrand.fr

Facility Name

Service de Chirurgie Digestive et de l'Urgence, CHU Albert Michallon

City

Grenoble

ZIP/Postal Code

38700

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Catherine ARVIEUX

Phone

(0)4 76 76 92 96

Ext

+33

carvieux@chu-grenoble.fr

Facility Name

Département de Chirurgie Cancérologique, Centre Léon Bérard

City

Lyon

ZIP/Postal Code

69373

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Patrice PEYRAT

Phone

(0)4 78 78 26 37

Ext

+33

patrice.peyrat@lyon.unicancer.fr

Facility Name

Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud

City

Pierre-Bénite

ZIP/Postal Code

69495

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Benoit You, MD

Phone

(0)4 78 86 43 18

Ext

+33

benoit.you@chu-lyon.fr

Facility Name

Service Oncologie Médicale, INSTITUT DE CANCEROLOGIE DE LA LOIRE (ICL)

City

Saint-Priest-en-Jarez

ZIP/Postal Code

42270

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Léa SABAN-ROCHE

Phone

(0)4 77 91 70 21

Ext

+33

léa.saban-roche@icloire.fr

Facility Name

Service de Chirurgie Digestive et Cancérologique, CHU NORD

City

Saint-Étienne

ZIP/Postal Code

42055

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jack PORCHERON

Phone

(0)4 77 82 83 37

Ext

+33

jack.porcheron@chu-st-etienne.fr

First Name & Middle Initial & Last Name & Degree

Karine ABBOUD

Phone

(0)4 77 12 77 17

Ext

+33

karine.abboud@chu-st-etienne.fr

First Name & Middle Initial & Last Name & Degree

Karine ABBOUD

12. IPD Sharing Statement

Learn more about this trial

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

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