Study the pharmacokinetics of Paclitaxel in patients from different BMI groups after administration of chemotherapy

Recruiting

• Conditions: Histologically or cytologically confirmed malignancy of the Breast or Ovary with ECOG 0-1,Treatment planned with Paclitaxel at dose of 175mg perm2

• Registration Number: CTRI/2015/09/006193
• Lead Sponsor: Tata Memorial Hospital

Brief Summary

We propose a study which will evaluate the pharmacokineticand toxicity profile of Paclitaxel administered in a population of women fromdifferent groups stratified as per the body mass index (BMI). The study aimsevaluate the pharmacokinetics and toxicity of Paclitaxel when administered asper the current practice at our institute.

 Paclitaxel is selected for this study since bothhematological and non-hematological toxicity of paclitaxel has been shown tocorrelate with parameters such as AUC, Cmax and duration of plasmaconcentrations exceeding 0.1 umol/L.(6)

 Historically,elimination of paclitaxel from plasma was determined to be biphasic with linearpharmacokinetic behaviour. These early studies, however, used variable infusionschedules of the drug with 1-, 6-, and 24-h infusions, and were hampered bysuboptimal analytical techniques. Currently with better techniques elimination of paclitaxel has been found to have athree-phase elimination curve and non-linear pharmacokinetic behavior,particularly with shorter infusions. Typical values reported for the α, β, andgamma (γ) half-lives are 0.19h (range0.01–0.40), 1.90h (range 0.50–2.80), and20.70h (range 4.00–65.00), respectively.(7)

 Paclitaxel exhibits non-linear pharmacokinetics in that ithas a disproportionate increase in the maximal plasma concentration Cmax) andarea under the concentration curve (AUC) as the dose increased, suggestingsaturation of elimination at higher concentrations of paclitaxel. Severalstudies with paclitaxel given as a 6-h infusion have documented non linearpharmacokinetics with doses higher than 250mg/m2. While others believe that alesser dose of 135mg/m2 is the critical threshold for non-linear kinetics.Similar ï¬ndings were noted with 3-h infusion schedules.(8)

 Paclitaxel is bound to proteins in plasma, tissues, andtubulins. Estimates of magnitude of protein binding reach as high as 98% withequilibrium dialysis and ultracentrifugation studies. Supporting extensive drugbinding in vivo, total volumes of distribution have been reported assigniï¬cantly larger than that of total body water ranging from 50L/m2  to over 650L/m2 depending on infusionarrangement.(8)

Detailed Description

Not available

Study Timeline

• Study Start: 2014-07-16
• Last Update Posted: 2015-09-16

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: Female
• Target Recruitment: 36

Inclusion Criteria

• 1.Female patient ≥ 18 years of age.
• 2.Written informed consent must be obtained prior to any study related procedures.
• 3.Life expectancy of at least 3 months.
• 4.Histologically or cytologically confirmed malignancy of the Breast or Ovary.
• 5.Treatment planned with Paclitaxel at a dose of 175mg/m2 to be administered over 3 hours.
• 6.Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• 7.Adequate hematologic function (ANC  1500 cells/µL: Hemoglobin  9 gm/dl, Platelets  1.0 lakh/mm3).
• 8.Adequate renal function (Serum creatinine ï‚£ 1.5 x ULN, if creatinine more than 1.0 x ULN and less or equal to 1.5 x ULN, calculated creatinine clearance according to CKD-EPI formula should be equal or more than 40 ml/min).
• 9.Serum bilirubin ï‚£ 1.0 x ULN, ALT ï‚£ 2.5 x ULN, AST ï‚£ 2.5 x ULN).
• If liver metastasis is present ALT ï‚£ 5 x ULN, AST ï‚£ 5 x ULN.
• 10.Female patients must have a negative serum pregnancy test at baseline (not applicable to patients with bilateral oophrectomy and/ or hysterectomy or to those patients who are > 1 year postmenopausal).
• 11.All patients of reproductive age group must agree to use of an approved form of contraception.
• 12.Should have completed at least 3 weeks from last chemotherapy.
• 14.Previous radiotherapy site should have included <25% of the total bone marrow.

Exclusion Criteria

• 1.Known allergy to taxanes.
• 2.Grade 2 or higher peripheral neuropathy (e.g. numbness, tingling and/or pain in distal extremities.
• 3.Symptomatic or clinically active CNS disease or metastatic lesions (prior radiotherapy to brain metastases is allowed).
• 4.Major surgery within last 4 weeks and end of prior radiotherapy within last 6 weeks.
• 5.Pregnant or breast feeding women.
• 6.Uncontrolled intercurrent disease (diabetes, hypertension, thyroid disease).
• 7.Any history of angina pectoris, coronary artery disease or cerebrovascular disease or transient ischemic attack.
• 8.Cardiac arrhythmia requiring medical therapy.
• 9.Known chronic infection with HIV, Hepatitis B and C.
• 10.Patients unwilling to comply with the study procedures.
• 11.Prior radiotherapy involving the entire pelvis.
• 12.Presence of third space fluid (ascitis or pleural effusion) which cannot be removed completely before the study drug administration.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1.Study the pharmacokinetics of Paclitaxel in patients from different BMI groups after standard administration of chemotherapy.	Comparison of the pharmacokinetic data will be carried out by the difference in mean approach. A population PK analysis will be carried out involving all enrolled patients
Difference in AUC between the two groups	Comparison of the pharmacokinetic data will be carried out by the difference in mean approach. A population PK analysis will be carried out involving all enrolled patients

Secondary Outcome Measures

Name	Time	Method
1.Variables affecting the clearance and Vd of paclitaxel would be determined using NONMEM	2.Toxicity will be reported as per CTCAE v 4.3 and analyzed descriptively.

Trial Locations

Locations (2)

ACTREC; 🇮🇳 (Suburban), MAHARASHTRA, India

Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

ACTREC

🇮🇳(Suburban), MAHARASHTRA, India

Dr Vikram Gota

Principal investigator

02227405470

vgota@actrec.gov.in