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

Cancer Clinical Trial

— PAL-ANGI2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01374620
• Other study ID #: PAL-ANGI2
• Status: Completed
• Phase: Phase 1
• First received: June 14, 2011
• Last updated: July 28, 2016
• Start date: June 2011
• Est. completion date: April 2013

Study information

• Verified date: July 2016
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

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

Locations

Country	Name	City	State
France	Centre Oscar Lambret	Lille

Sponsors (1)

Lead Sponsor	Collaborator
Centre Oscar Lambret

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: 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	Yes
Secondary	Description of the nature of adverse events	According to the NCI-CTCAE scale v4.0	During the study treatment, an expected average of 2 months	Yes
Secondary	Evaluation of objective response after 2 cycles	Objective response (complete response, partial response and stable disease) according to RECIST 1.1 criteria	After 2 cycles = 2 months	No
Secondary	Estimation of the free-progression median time	Time between the inclusion and the disease progression (clinical or radiological)	Until disease progression	No
Secondary	Calculation of the Growth Modulation Index (GMI)	Time to progression on study treatment and time to progression on prior treatment	Until disease progression	No
Secondary	Evaluation of the correlation between clinical response and biological parameters	Biological parameters related to angiogenesis	Day 1, 8, 15, 21 of cycle 1 and cycle 2	No
Secondary	Description of the severity of adverse events	According to the NCI-CTCAE scale v4.0	During the study treatment, an expected average of 2 months	Yes