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

NCT02866903 | Unknown Phase 1 DMC

• 1 other identifier: 69HCL16_0134
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 6

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.

Conditions

Peritoneal Carcinosis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  up to 14 days

• Dose Limiting Toxicities, DLT

  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 Outcomes (5)

• Overall response rate according to RECIST

  up to 4 months

• Peritoneal Cancer Index (PCI)

  up to 4 months

• Adverse events (NCI CTCAE v4.0)

  up to 5 months

• The quality of life (EORTC QLQ-C30)

  up to 4 months

• The quality of life (EORTC QLQ-C29)

  up to 4 months

Study Arms (1)

Patients with peritoneal carcinosis

EXPERIMENTAL

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

Interventions

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

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

Patients with peritoneal carcinosis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (6)

CHU Estaing

Clermont-Ferrand, 63003, France

NOT YET RECRUITING

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

Grenoble, 38700, France

NOT YET RECRUITING

Département de Chirurgie Cancérologique, Centre Léon Bérard

Lyon, 69373, France

NOT YET RECRUITING

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

Pierre-Bénite, 69495, France

RECRUITING

Service de Chirurgie Digestive et Cancérologique, CHU NORD

Saint-Etienne, 42055, France

NOT YET RECRUITING

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

Saint-Priest-en-Jarez, 42270, France

NOT YET RECRUITING

MeSH Terms

Interventions

Infusions, Parenteral; Oxaliplatin

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Coordination Complexes; Organic Chemicals

Study Officials

• Benoit You, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benoit You, MD

CONTACT

(0)4 78 86 43 18; benoit.you@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 15, 2016
• Study Start: May 18, 2017
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: September 21, 2017

Record last verified: 2017-09

Locations

FR (6)