Phase I Study : Dose Escalation of Intravenous Weekly Paclitaxel in Association With Metronomic Administration of Cyclophosphamide
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Centre Oscar Lambret
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Determination of the iv paclitaxel maximum tolerated dose and recommended dose in association with a fixed dose of oral cyclophosphamide
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 clearance > 60 ml/min (Cockcroft 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)
Arms & Interventions
Paclitaxel Dose escalation
A standard dose escalation strategy will be used including 3 to 6 patients at each dose level (Paclitaxel dose escalation + fixed dose of cyclophosphamide)
+ blood collection
Intervention: Paclitaxel dose escalation (Drug)
Paclitaxel Dose escalation
A standard dose escalation strategy will be used including 3 to 6 patients at each dose level (Paclitaxel dose escalation + fixed dose of cyclophosphamide)
+ blood collection
Intervention: Cyclophosphamide (Drug)
Paclitaxel Dose escalation
A standard dose escalation strategy will be used including 3 to 6 patients at each dose level (Paclitaxel dose escalation + fixed dose of cyclophosphamide)
+ blood collection
Intervention: Blood collection (Biological)
Cohort extension
An additional 10 patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose
+ blood collection
Intervention: Paclitaxel (Drug)
Cohort extension
An additional 10 patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose
+ blood collection
Intervention: Cyclophosphamide (Drug)
Cohort extension
An additional 10 patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose
+ blood collection
Intervention: Blood collection (Biological)
Outcomes
Primary Outcomes
Determination of the iv paclitaxel maximum tolerated dose and recommended dose in association with a fixed dose of oral cyclophosphamide
Time Frame: 28 days = cycle 1
A DLT is defined below: Hematological toxicity: * Polynuclear neutrophils \< 500/mm3 for more than 7 days * Febrile neutropenia (Polynuclear neutrophils \< 1 000/mm3 and fever \> or = 38.5°C) or documented infection * Thrombopenia (Platelets \< 25 000/mm3) * Impossibility to administer D8 or D15 due to hematological criteria Non-hematological toxicity: Any grade 3 or 4 toxicity related to study treatment, with the exception of fatigue and alopecia
Secondary Outcomes
- Evaluation of objective response after 2 cycles(After 2 cycles = 2 months)
- Description of the severity of adverse events(During the study treatment, an expected average of 2 months)
- Description of the nature of adverse events(During the study treatment, an expected average of 2 months)
- Estimation of the free-progression median time(Until disease progression)
- Calculation of the Growth Modulation Index (GMI)(Until disease progression)
- Evaluation of the correlation between clinical response and biological parameters(Day 1, 8, 15, 21 of cycle 1 and cycle 2)