Clinical trial NCT02866903: Safety of Intraperitoneal (IP) OXAliplatin (OXA) in Association With Systemic FOLFIRI Bevacizumab Chemotherapy in Patients With Peritoneal Carcinosis
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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Peritoneal Carcinosis
Keywords: Peritoneal carcinosis
intraperitoneal (IP) OXAliplatin
Phase I/II dose escalation trial
FOLFIRI Bevacizumab chemotherapy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Adverse events (NCI CTCAE v4.0)
timeFrame: up to 14 days
measure: Dose Limiting Toxicities, DLT
timeFrame: up to 14 days
Secondary outcomes:
measure: Overall response rate according to RECIST
timeFrame: up to 4 months
measure: Peritoneal Cancer Index (PCI)
timeFrame: up to 4 months
measure: Adverse events (NCI CTCAE v4.0)
timeFrame: up to 5 months
measure: The quality of life (EORTC QLQ-C30)
timeFrame: up to 4 months
measure: The quality of life (EORTC QLQ-C29)
timeFrame: up to 4 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Grenoble
country: France
facility: Service de Chirurgie Digestive et de l'Urgence, CHU Albert Michallon
city: Lyon
country: France
facility: Département de Chirurgie Cancérologique, Centre Léon Bérard
city: Pierre-Bénite
country: France
facility: Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud
city: Saint-Priest-en-Jarez
country: France
facility: Service Oncologie Médicale, INSTITUT DE CANCEROLOGIE DE LA LOIRE (ICL)
city: Saint-Étienne
country: France
facility: Service de Chirurgie Digestive et Cancérologique, CHU NORD
Study officials:
affiliation: Service d'Oncologie Médicale, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud 69495 Pierre-Bénite
name: Benoit You, MD
role: PRINCIPAL_INVESTIGATOR
References: