Cancer
Conditions
Keywords
Cancer
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
Interventions
DRUGPaclitaxel dose escalation
Paclitaxel will be administered intravenously over 60 minutes, at D1, D8 and D15, at a given dose. The Paclitaxel dose (mg/infusion) levels are as follows: * 40 * 60 * 70 * 75 * 80 * 85 * 90
DRUGPaclitaxel
Patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose in association with metronomic cyclophosphamide
DRUGCyclophosphamide
D1 to D28: 50 mg x 2/day/cycle 1 cycle = 28 days
BIOLOGICALBlood collection
At D1, D8, D15 and D21 of cycle 1 and cycle 2:2 blood samples for the correlation between clinical response and biological parameters
Sponsors
Centre Oscar Lambret
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the iv paclitaxel maximum tolerated dose and recommended dose in association with a fixed dose of oral cyclophosphamide | 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
| Measure | Time frame | Description |
|---|---|---|
| Description of the nature of adverse events | During the study treatment, an expected average of 2 months | According to the NCI-CTCAE scale v4.0 |
| Evaluation of objective response after 2 cycles | After 2 cycles = 2 months | Objective response (complete response, partial response and stable disease) according to RECIST 1.1 criteria |
| Estimation of the free-progression median time | Until disease progression | Time between the inclusion and the disease progression (clinical or radiological) |
| Calculation of the Growth Modulation Index (GMI) | Until disease progression | Time to progression on study treatment and time to progression on prior treatment |
| Evaluation of the correlation between clinical response and biological parameters | Day 1, 8, 15, 21 of cycle 1 and cycle 2 | Biological parameters related to angiogenesis |
| Description of the severity of adverse events | During the study treatment, an expected average of 2 months | According to the NCI-CTCAE scale v4.0 |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORNicolas PENEL, MD
Centre Oscar Lambret
Outcome results
None listed