Weekly Paclitaxel and Cyclophosphamide in Metronomic Administration : Dose Escalation Study of Weekly Paclitaxel (PAL-ANGI2)

Centre Oscar Lambret

Status and phase: Completed; Phase 1

Conditions: Cancer

Treatments: Drug: Paclitaxel; Drug: Cyclophosphamide; Drug: Paclitaxel dose escalation; Biological: Blood collection

Study type: Interventional

Funder types: Other

Identifiers

NCT01374620

PAL-ANGI2

Details and patient eligibility

About

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

Full 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

Enrollment: 28 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Paclitaxel Dose escalation

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Biological: Blood collection

Drug: Paclitaxel dose escalation

Cohort extension

Experimental group

Description:

An additional 10 patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose + blood collection

Treatment:

Drug: Cyclophosphamide

Biological: Blood collection

Drug: Paclitaxel