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

July 28, 2016 updated by: Centre Oscar Lambret

Phase I Study : Dose Escalation of Intravenous Weekly Paclitaxel in Association With Metronomic Administration of Cyclophosphamide

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59000
        • Centre OSCAR LAMBRET

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: Paclitaxel 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
Other Names:
  • Taxol
Drug: Cyclophosphamide

D1 to D28: 50 mg x 2/day/cycle

1 cycle = 28 days

Other Names:
  • Endoxan
Biological: Blood 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
Experimental: Cohort extension

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

+ blood collection
Drug: Cyclophosphamide

D1 to D28: 50 mg x 2/day/cycle

1 cycle = 28 days

Other Names:
  • Endoxan
Biological: Blood 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
Drug: Paclitaxel
Patients will be treated at the recommended dose in order to confirm the recommended paclitaxel dose in association with metronomic cyclophosphamide
Other Names:
  • Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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:

  • Polunuclear neutrophils < 500/mm3 for more than 7 days
  • Febrile neutropenia (Polunuclear 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 critera

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Description of the nature of adverse events
Time Frame: During the study treatment, an expected average of 2 months
According to the NCI-CTCAE scale v4.0
During the study treatment, an expected average of 2 months
Evaluation of objective response after 2 cycles
Time Frame: After 2 cycles = 2 months
Objective response (complete response, partial response and stable disease) according to RECIST 1.1 criteria
After 2 cycles = 2 months
Estimation of the free-progression median time
Time Frame: Until disease progression
Time between the inclusion and the disease progression (clinical or radiological)
Until disease progression
Calculation of the Growth Modulation Index (GMI)
Time Frame: Until disease progression
Time to progression on study treatment and time to progression on prior treatment
Until disease progression
Evaluation of the correlation between clinical response and biological parameters
Time Frame: Day 1, 8, 15, 21 of cycle 1 and cycle 2
Biological parameters related to angiogenesis
Day 1, 8, 15, 21 of cycle 1 and cycle 2
Description of the severity of adverse events
Time Frame: During the study treatment, an expected average of 2 months
According to the NCI-CTCAE scale v4.0
During the study treatment, an expected average of 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Oscar Lambret

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

June 14, 2011

First Submitted That Met QC Criteria

June 15, 2011

First Posted (Estimate)

June 16, 2011

Study Record Updates

Last Update Posted (Estimate)

July 29, 2016

Last Update Submitted That Met QC Criteria

July 28, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PAL-ANGI2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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