| CTRI Number |
CTRI/2015/09/006193 [Registered on: 17/09/2015] Trial Registered Retrospectively |
| Last Modified On: |
16/09/2015 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Other (Specify) [Comparative Pharmacokinetic] |
| Study Design |
Other |
|
Public Title of Study
|
Study the pharmacokinetics of Paclitaxel in patients from different BMI groups after administration of chemotherapy |
|
Scientific Title of Study
|
A Prospective, open label, non randomized, comparative pharmacokinetic study of Paclitaxel pharmacokinetics in women with different Body Mass Index undergoing chemotherapy for breast and ovarian cancer. |
| Trial Acronym |
Paclitaxel PK Study |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| IECProject No.1217 Version#1.1 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Sudeep Gupta |
| Designation |
Principal Investigator |
| Affiliation |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital,
Department of Medical Oncology,
Dr.E.Borges Road,
Parel,Mumbai
ACTREC,Department of Clinical Pharmacology,Tata Memorial Centre,Kharghar,Navi Mumbai,
India 410210
Mumbai
MAHARASHTRA
400012
India |
| Phone |
02224177201 |
| Fax |
|
| Email |
sudeepgupta04@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr J V Divatia |
| Designation |
Member Secretary |
| Affiliation |
Tata Memorial Hospital |
| Address |
Institutional Ethics Committee(I.E.C.),
Tata Memorial Hospital,
3rd Floor,Main Building,
Dr.E.Borges Road,Parel(EAST),
Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
02224177262 |
| Fax |
|
| Email |
tmhethics@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr J V Divatia |
| Designation |
Member Secretary |
| Affiliation |
Tata Memorial Hospital |
| Address |
Institutional Ethics Committee(I.E.C.),
Tata Memorial Hospital,
3rd Floor,Main Building,
Dr.E.Borges Road,Parel(EAST),
Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
02224177262 |
| Fax |
|
| Email |
tmhethics@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Tata Memorial Hospital,
Dr E Borges Road,Parel,
Mumbai 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Vikram Gota |
ACTREC |
ACTREC, Tata Memorial Centre, K.S 102 1st floor, Clinical Pharmacology Department, Kharghar - 410210, Navi Mumbai
Mumbai (Suburban)
MAHARASHTRA |
02227405470
02224177201
vgota@actrec.gov.in |
| Dr Sudeep Gupta |
Tata Memorial Hospital |
Tata Memorial Hospital
11th floor Room No 1109,Homi bhabha block
Dr E Borges Road,
Parel,
Mumbai 400012
Mumbai
MAHARASHTRA |
02224177201
02224177201
sudeepgupta04@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Histologically or cytologically confirmed malignancy of the Breast or Ovary with ECOG 0-1,Treatment planned with Paclitaxel at dose of 175mg perm2, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Inj.Paclitaxel |
175mg/m2 to be administered over 3 hours every 21 days |
| Comparator Agent |
NOT APPLICABLE |
NOT APPLICABLE |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Female |
| Details |
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.
13. Should have completed at least 6 weeks from last radiotherapy.
14. Previous radiotherapy site should have included <25% of the total bone marrow.
|
|
| ExclusionCriteria |
| Details |
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.
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
1. Study the pharmacokinetics of Paclitaxel in patients from different BMI groups after standard administration of chemotherapy.
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
|
| Outcome |
TimePoints |
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.
|
Clinical evaluation and toxicity assessment will be done on day8 day21 of all the enrolled patients |
|
|
Target Sample Size
|
Total Sample Size="36"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
16/07/2014 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
We propose a study which will evaluate the pharmacokinetic
and toxicity profile of Paclitaxel administered in a population of women from
different groups stratified as per the body mass index (BMI). The study aims
evaluate the pharmacokinetics and toxicity of Paclitaxel when administered as
per the current practice at our institute.
Paclitaxel is selected for this study since both
hematological and non-hematological toxicity of paclitaxel has been shown to
correlate with parameters such as AUC, Cmax and duration of plasma
concentrations exceeding 0.1 umol/L.(6)
Historically,
elimination of paclitaxel from plasma was determined to be biphasic with linear
pharmacokinetic behaviour. These early studies, however, used variable infusion
schedules of the drug with 1-, 6-, and 24-h infusions, and were hampered by
suboptimal analytical techniques. Currently with better techniques elimination of paclitaxel has been found to have a
three-phase elimination curve and non-linear pharmacokinetic behavior,
particularly with shorter infusions. Typical values reported for the α, β, and
gamma (γ) half-lives are 0.19h (range0.01–0.40), 1.90h (range 0.50–2.80), and
20.70h (range 4.00–65.00), respectively.(7)
Paclitaxel exhibits non-linear pharmacokinetics in that it
has a disproportionate increase in the maximal plasma concentration Cmax) and
area under the concentration curve (AUC) as the dose increased, suggesting
saturation of elimination at higher concentrations of paclitaxel. Several
studies with paclitaxel given as a 6-h infusion have documented non linear
pharmacokinetics with doses higher than 250mg/m2. While others believe that a
lesser 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, and
tubulins. Estimates of magnitude of protein binding reach as high as 98% with
equilibrium dialysis and ultracentrifugation studies. Supporting extensive drug
binding in vivo, total volumes of distribution have been reported as
signiï¬cantly larger than that of total body water ranging from 50L/m2 to over 650L/m2 depending on infusion
arrangement.(8)
|