Clinical trial NCT01374620: Weekly Paclitaxel and Cyclophosphamide in Metronomic Administration : Dose Escalation Study of Weekly Paclitaxel
Official title: Phase I Study : Dose Escalation of Intravenous Weekly Paclitaxel in Association With Metronomic Administration of Cyclophosphamide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Cancer
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
First posted: 2011-06-16
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study is to determine the MTD of Paclitaxel in association with metronomic Cyclophosphamide.

Detailed description: The aim of the study is to determine the MTD of Paclitaxel in association with metronomic Cyclophosphamide for cancer which present no therapeutic solution

Eligibility criteria: Inclusion Criteria:

* Patient with cancer histologically proved
* No other therapeutic proposal after discussion in multidisciplinary consultation
* Radiological evidence of the evolving nature of the disease
* Measurable disease with at least one measurable lesion according to the criteria RECIST 1.1
* At least 28 days since prior treatment(systemic treatment or major surgery)
* Patient who have recovered from any previous toxicity
* Man or woman de ≥ 18 years and ≤ 65 years
* Performance Status (ECOG) ≤ 2 within 7 days before inclusion
* Polynuclear neutrophils ≥ 1500/mm3, platelets ≥ 100 000/mm3, Hemoglobin ≥ 9 g/dl
* Serum Albumin ≥ 36 g/l and lymphocytes ≥ 700/mm3
* Total bilirubin and SGPT/ALT and SGOT/AST ≤ 3 ULN(≤ 5 ULN if liver metastases)
* Creatinine in normal ranges and Creatinine clairance \> 60 ml/min (Cockroft formulae)
* Central venous access
* Negative pregnancy test for women who may be pregnant within 7 days before inclusion
* Effective contraceptive during the treatment period and up to 6 months after the end of treatment (for patients of both sexes during their reproductive and child-bearing age and their partners)
* Patient covered by government health insurance
* Informed consent signed by the patient before any specific study procedure

Exclusion Criteria:

* Prior treatment by Paclitaxel
* Oral treatment impossible
* Known dysphagia, malabsorption or maldigestion
* Pre-existing neuropathy clinically symptomatic
* Known leptomeningeal brain metastases
* Known allergy to Cremophor, to Paclitaxel or one of its excipients (especially polyoxyethylene castor oil), to Cyclophosphamide or one of its excipients (lactose, sucrose)
* Active and uncontrolled infection
* Acute urinary tract infection, pre-existing hemorrhagic cystitis
* Diabetes insipidus
* History or progressive psychiatric illness
* Persons under guardianship or detainees
* Unable for medical follow-up (geographic, social or mental reasons)
* Pregnant, or likely to be or breastfeeding women
* Absence of effective contraception for the duration of treatment and 6 months after completion of therapy (for patients of both sexes in childbearing or reproductive age and their partners)

Primary outcomes:
measure: Determination of the iv paclitaxel maximum tolerated dose and recommended dose in association with a fixed dose of oral cyclophosphamide
timeFrame: 28 days = cycle 1
Secondary outcomes:
measure: Description of the nature of adverse events
timeFrame: During the study treatment, an expected average of 2 months
measure: Evaluation of objective response after 2 cycles
timeFrame: After 2 cycles = 2 months
measure: Estimation of the free-progression median time
timeFrame: Until disease progression
measure: Calculation of the Growth Modulation Index (GMI)
timeFrame: Until disease progression
measure: Evaluation of the correlation between clinical response and biological parameters
timeFrame: Day 1, 8, 15, 21 of cycle 1 and cycle 2
measure: Description of the severity of adverse events
timeFrame: During the study treatment, an expected average of 2 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
Study officials:
affiliation: Centre Oscar Lambret
name: Nicolas PENEL, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pannier D, Adenis A, Bogart E, Dansin E, Clisant-Delaine S, Decoupigny E, Lesoin A, Amela E, Ducornet S, Meurant JP, Le Deley MC, Penel N. Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial. BMC Cancer. 2018 Jul 31;18(1):775. doi: 10.1186/s12885-018-4678-x.