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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01374620
First received: June 14, 2011
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention Phase
Cancer
Drug: Paclitaxel dose escalation
Drug: Paclitaxel
Drug: Cyclophosphamide
Biological: Blood collection
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study : Dose Escalation of Intravenous Weekly Paclitaxel in Association With Metronomic Administration of Cyclophosphamide

Resource links provided by NLM:


Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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



Secondary Outcome Measures:
  • Description of the nature of adverse events [ Time Frame: During the study treatment, an expected average of 2 months ] [ Designated as safety issue: Yes ]
    According to the NCI-CTCAE scale v4.0

  • Evaluation of objective response after 2 cycles [ Time Frame: After 2 cycles = 2 months ] [ Designated as safety issue: No ]
    Objective response (complete response, partial response and stable disease) according to RECIST 1.1 criteria

  • Estimation of the free-progression median time [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
    Time between the inclusion and the disease progression (clinical or radiological)

  • Calculation of the Growth Modulation Index (GMI) [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
    Time to progression on study treatment and time to progression on prior treatment

  • Evaluation of the correlation between clinical response and biological parameters [ Time Frame: Day 1, 8, 15, 21 of cycle 1 and cycle 2 ] [ Designated as safety issue: No ]
    Biological parameters related to angiogenesis

  • Description of the severity of adverse events [ Time Frame: During the study treatment, an expected average of 2 months ] [ Designated as safety issue: Yes ]
    According to the NCI-CTCAE scale v4.0


Estimated Enrollment: 64
Study Start Date: June 2011
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation
A standard dose escalation strategy will be used including 3 to 6 patients at each dose level.
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
Drug: Cyclophosphamide

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

1 cycle = 28 days

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

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

1 cycle = 28 days

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01374620

Locations
France
Centre Oscar Lambret
Lille, France, 59000
Sponsors and Collaborators
Centre Oscar Lambret
Investigators
Principal Investigator: Nicolas PENEL, MD Centre Oscar Lambret
  More Information

No publications provided

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01374620     History of Changes
Other Study ID Numbers: PAL-ANGI2
Study First Received: June 14, 2011
Last Updated: August 19, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Oscar Lambret:
Cancer

Additional relevant MeSH terms:
Cyclophosphamide
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 17, 2014