Weekly Paclitaxel and Cyclophosphamide in Metronomic Administration : Dose Escalation Study of Weekly Paclitaxel

NCT01374620 | Completed Phase 1 DMC

• 2 other identifiers: PAL-ANGI2-11012011-001155-36
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cancer

Keywords

Cancer

Outcome Measures

Primary Outcomes (1)

• Determination of the iv paclitaxel maximum tolerated dose and recommended dose in association with a fixed dose of oral cyclophosphamide

  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

  28 days = cycle 1

Secondary Outcomes (6)

• Description of the nature of adverse events

  During the study treatment, an expected average of 2 months

• Evaluation of objective response after 2 cycles

  After 2 cycles = 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

Study Arms (2)

Paclitaxel Dose escalation

EXPERIMENTAL

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

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

Cohort extension

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: Cyclophosphamide; Biological: Blood collection

Interventions

Paclitaxel DRUG

Patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose in association with metronomic cyclophosphamide

Also known as: Taxol

Cohort extension

Cyclophosphamide DRUG

D1 to D28: 50 mg x 2/day/cycle 1 cycle = 28 days

Also known as: Endoxan

Cohort extension; Paclitaxel Dose escalation

Blood collection BIOLOGICAL

At D1, D8, D15 and D21 of cycle 1 and cycle 2:2 blood samples for the correlation between clinical response and biological parameters

Cohort extension; Paclitaxel Dose escalation

Paclitaxel dose escalation DRUG

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

Also known as: Taxol

Paclitaxel Dose escalation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centre Oscar Lambret: lead

Study Sites (1)

Centre Oscar Lambret

Lille, 59000, France

Location

Related Publications (1)

• 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.

  PMID: 30064401 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Paclitaxel; Cyclophosphamide; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nicolas PENEL, MD

  Centre Oscar Lambret

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2011
• First Posted: June 16, 2011
• Study Start: July 13, 2011
• Primary Completion: February 1, 2013
• Study Completion: April 1, 2013
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)