CTRI/2020/03/024065 [Registered on: 19/03/2020] Trial Registered Prospectively
Last Modified On:
13/10/2020
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioavailability Study of Paclitaxel Injection Concentrate for Suspension in Subjects with Locally Recurrent or Metastatic Breast Cancer.
Scientific Title of Study
A Randomized, Open Label, Two Period, Single Dose, Crossover, Bioavailability Study of Paclitaxel Injection Concentrate for Suspension (PICS) in Subjects with Locally Recurrent or Metastatic Breast Cancer (MBC).
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
SDO-006-20-01, Version 01, Amendment 00, 06 Feb 2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Institutional Review Board, Mahatma Gandhi Cancer Hospital and Research Institute
Submittted/Under Review
Kolhapur Cancer Centre Institutional Ethics Committee
Submittted/Under Review
Manavata Clinical Research Institute Ethics Committee
Approved
Medstar Speciality Hospital Ethics Committee
Submittted/Under Review
Narsimha Saraswati Medical Foundation, Indrayani Hospital and Research Institute
Approved
Noble Hospital Institutional Ethics
Approved
Shatabdi Hospital Ethics Committee
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
NOT APPLICABLE
NOT APPLICABLE
Intervention
SPARC study medication reconstituted with either Method 1 or Method 2
dose: 260mg/m2
Frequency: 2 period cross over study
Route of administration : intravenous infusion
duration of therapy: Approximately 6 to 8 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. The subject has given written, informed consent (or legally acceptable representative /impartial witness when applicable) and is available for the duration of study
2. Histologically or cytologically confirmed diagnosis of breast cancer with adequate documentation of prior therapy with an anthracycline unless clinically contraindicated
3. Locally recurrent or MBC for which taxane-based therapy is an appropriate treatment option
4. Male or female aged greater than equal to 18 years
5. ECOG performance status less than equal to 1
6. Estimated life expectancy of at least 12 weeks
7. Adequate organ and immune system function as indicated by the following laboratory values, obtained less than equal to 2 weeks prior to dosing for Period 1 and Period 2:
8. Any chemotherapy, targeted therapy, major surgery, or irradiation must have been completed at least 4 weeks before enrollment (6 weeks for mitomycin C or nitrosurea); immune therapy or hormonal therapy (except palliative bisphosphonate therapy for bone pain) must be completed 2 weeks before enrollment and subjects must have recovered from all toxicities incurred as a result of previous therapy except alopecia; use of targeted therapy or antibody therapy should have been completed for at least 5 half-lives of the respective therapy before enrollment. Use of narcotic analgesics such as dihydrocodeine and medicinal herbs such as St. John’s Wort, which may act as inhibitors/inducers of CYP2C8 and CYP3A4, must have been discontinued at least 2 weeks and 4 weeks respectively before enrollment
9. Subjects of child bearing potential must practice an acceptable method of birth control as judged by the investigator
• Medically acceptable methods of birth control include the use of either a contraceptive implant or a contraceptive injection (e.g., Depo-Provera™) or an intrauterine device, same sex partner or vasectomized partner or an oral contraceptive taken continually within the past three months and which the subject agrees to continue using during the study
• To adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or a spermicide at least 2 months prior to study entry and must continue to use contraception for the duration of the study
10. Female subjects who are postmenopausal for at least 1 year as per investigator’s discretion, or who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject)
11. Male subjects enrolled in the trial cannot father a child and are advised to prevent passage of semen to their sexual partner during intercourse using acceptable methods as judged by the investigator for the duration of the study
12. Females subjects of child-bearing potential must have a negative urine pregnancy test
13. Female subjects must be non-lactating and non-breastfeeding
14. Subject must be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
ExclusionCriteria
Details
1. Known hypersensitivity to the study drug or their excipients (cholesteryl sulfate, caprylic acid, polyvinylpyrrolidone, ethanol, polyethylene glycol)
2. Inability to undergo venipuncture and/or tolerate venous access
3. Presence of clinically symptomatic active CNS metastases, including leptomeningial involvement, requiring steroid or radiation therapy
4. Pre-existing clinically significant peripheral neuropathy (Grade 2 or higher according to CTCAE, Version 5.0)
5. Any other severe concurrent disease which in the judgment of the investigator would make the subject inappropriate for entry into this study or confound the study
6. Presence of pleural/ascitic fluid which cannot be definitively treated prior to dosing and during the PK blood draws in each period (Period 1 and Period 2) and if there is re-accumulation of fluid (greater than 5%) greater than 2 weeks after definitive management
7. Positive laboratory exclusion test (HIV, HBsAg, or HCV)
8. Treatment with investigational agents or participation in a clinical trial within 30 days of study entry
9. Failure of prior taxane therapy for metastatic disease or for adjuvant therapy within previous 6 months of screening visit
10. Subjects taking concurrent medications that may act as inhibitors/inducers of CYP2C8 and CYP3A4 within 2 weeks of screening and during Periods 1 and 2
11. Evidence or history of bleeding diathesis or coagulopathy within 6 months prior to screening visit
12. Uncontrolled cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA), history of hypertensive crisis
13. Active clinical infection which in the treating investigator’s opinion renders the subject ineligible or can confound the study
14. Serious non-healing wound, ulcer or bone fracture
15. Unresolved toxicity higher than CTCAE Version 5.0 Grade 1 (excluding alopecia, anemia) attributed to any prior therapy/procedure
16. History of gastrointestinal perforation within 6 months prior to screening visit.
Method of Generating Random Sequence
Other
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Maximum observed plasma concentration Plasma, area under the plasma concentration versus time curve, from time 0 to the last measurable concentration and area under the plasma concentration versus time curve from time 0 to infinity of PICS under various reconstitution conditions.
8 weeks
Secondary Outcome
Outcome
TimePoints
number of subjects with treatment emergent adverse events
safety and tolerability profile of PICS under various reconstitution conditions
8 weeks
Target Sample Size
Total Sample Size="44" Sample Size from India="44" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a randomized, multi center, open label, two-period, single dose, crossover study to evaluate the bioavailability and safety of PICS in Locally Recurrent or Metastatic Breast Cancer subjects.