Weekly Paclitaxel and Cyclophosphamide in Metronomic Administration : Dose Escalation Study of Weekly Paclitaxel (PAL-ANGI2)
This study is currently recruiting participants.
Verified February 2013 by Centre Oscar Lambret
Sponsor:
Centre Oscar Lambret
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01374620
First received: June 14, 2011
Last updated: February 12, 2013
Last verified: February 2013
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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 2014 |
| Estimated 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:
D1 to D28: 50 mg x 2/day/cycle 1 cycle = 28 days 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 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
Contacts
| Contact: Nicolas PENEL, MD | 03.20.29.59.20 | n-penel@o-lambret.fr |
| Contact: Yvette VENDEL, CRA | 03.20.29.59.40 | y-vendel@o-lambret.fr |
Locations
| France | |
| Centre Oscar Lambret | Recruiting |
| Lille, France, 59000 | |
| Contact: Nicolas PENEL, MD, PhD +33 (0)3 20 29 59 18 n-penel@o-lambret.fr | |
| Principal Investigator: Nicoals PENEL, MD, PhD | |
| Sub-Investigator: Antoine ADENIS, MD, PhD | |
| Sub-Investigator: Jacques BONNETERRE, MD, PhD | |
| Sub-Investigator: Eric DANSIN, MD | |
| Sub-Investigator: Sophie DOMINGUEZ, MD | |
| Sub-Investigator: Dominique HOGUET, MD | |
| Sub-Investigator: Audrey MAILLIEZ, MD | |
| Sub-Investigator: Laurence VANLEMMENS, MD | |
| Sub-Investigator: Eric AMELA, MD | |
| Sub-Investigator: Véronique SERVENT, MD | |
| Sub-Investigator: Philippe VENNIN, MD | |
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: | February 12, 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 May 21, 2013