PK and Safety Study of Paclitaxel Injection Concentrate for Nano-dispersion Administered Weekly

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Sun Pharma Advanced Research Company Limited
Sponsor:
Information provided by (Responsible Party):
Sun Pharma Advanced Research Company Limited
ClinicalTrials.gov Identifier:
NCT01305512
First received: February 24, 2011
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

This is a phase I study of PICN weekly administration and will use a '3+3' dose escalation design to determine the MTD and recommend phase II dose of PICN weekly. PICN will be administered over 30-min infusion once a week for 3 weeks, followed by 1 week of rest. This will comprise one cycle of PICN administration. The pharmacokinetic profile of PICN will be evaluated over 6 dose levels for one cycle in each dose level.


Condition Intervention Phase
Solid Tumor in Advanced Stage
Drug: Paclitaxel Injection Concentrate for Nanodispersion
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Pharmacokinetic (PK), Safety, and Tolerability Study of Paclitaxel Injection Concentrate for Nano-dispersion (PICN) Administered Weekly in Subjects With Advanced Solid Malignancies in US Population.

Resource links provided by NLM:


Further study details as provided by Sun Pharma Advanced Research Company Limited:

Primary Outcome Measures:
  • Determination of Maximum Tolerated Dose (MTD) during dose escalation [ Time Frame: One 21-day treatment cycle ] [ Designated as safety issue: Yes ]
    MTD for PICN will be determined as dose below the dose at which DLT (Dose Limiting Toxicity) is seen for ≥ 2 subjects


Secondary Outcome Measures:
  • Establishing pharmacokinectic profile at each dose level for PICN [ Time Frame: One 21-day treatment cycle ] [ Designated as safety issue: No ]
    Plasma levels of PICN will be determined and PK parameters viz., Cmax, AUC0-t, AUC0-∞, MRT, Tmax, t½, Kel, Vd, Cl for PICN will be evaluated


Estimated Enrollment: 36
Study Start Date: July 2012
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Paclitaxel Injection Concentrate for Nanodispersion

    PICN infusion will be prepared by diluting 5% dextrose Injection to obtain a nano-dispersion and infused using conventional PVC infusion systems.

    PICN will be administered as 30-minute intravenous infusion on days 1, 8, and 15 of each 4-week cycle - once a week for 3 weeks, followed by 1 week of rest (one cycle)until disease progression, development of unacceptable toxicities, non-compliance, inter-current illness that prevents treatment continuation, withdrawal of consent, or change in subject condition that render the subject unacceptable for further treatment.

Detailed Description:

This is a phase I study of PICN that will use the standard '3+3'dose-escalation design to determine the MTD and recommend phase II dose of PICN administered once a week for 3 weeks, followed by 1 week of rest. PICN will be administered as 30-minute intravenous infusion on days 1, 8, and 15 of each 4-week cycle - once a week for 3 weeks, followed by 1 week of rest (one cycle). Next cycle dosing will open on day 28 after laboratory investigations are done of the previous cycle. Subjects will continue therapy until disease progression, development of unacceptable toxicities, non-compliance, inter-current illness that prevents treatment continuation, withdrawal of consent, or change in patient condition that render the patient unacceptable for further treatment. There are 6 dose levels planned for dose escalation. The dose escalation plan is as follows: Three subjects will be treated at the initial dose level for PICN. If no Cycle-1 dose-limiting toxicities (DLTs) are observed, 3-new subjects will be treated at the next dose level. If one of three subjects experiences a DLT at any given dose level, three additional subjects will be treated at that same dose. If a DLT occurred in at least two subjects at any dose level, dose escalation will be halted, and the next three subjects enrolled will be treated at the preceding lower dose level. MTD will be defined as the highest PICN dose at which DLT (Dose Limiting Toxicity) is seen in <2 subjects out of 6. Subjects who fail to complete 1 cycle of study treatment for non-treatment related reasons will be replaced.

AEs will be monitored across all cycles per CTCAE 4.0 and disease response will be assessed by imaging at baseline and on day 1 of cycle 3, 5, and 7 as per RECIST 1.1. Upon study completion, subjects will be followed for toxicities for 4 weeks, or longer if there are unresolved ≥ grade 3 toxicities at the end of the 4-week period. Subjects removed from study for unacceptable adverse events will be followed until resolution (≤ grade 2) or stabilization of the adverse events. Blood samples for pharmacokinetic studies will be collected at pre-planned time-points.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of solid tumor in advanced stage which taxane-based therapy is a rational treatment option.
  • Age ≥18 years
  • ECOG Performance Status ≤ 1.
  • Estimated life expectancy of at least 12-weeks;
  • Measurable disease as per RECIST guideline (Version 1.1);
  • Adequate organ and immune system function as indicated by laboratory tests obtained ≤ 2 weeks prior to dosing.
  • Women of child bearing potential practicing an acceptable method of birth control.
  • Willing to participate and give written informed consent.

Exclusion Criteria:

  • Any malignancy within past 5-years, except non-melanoma skin cancer, cervical intraepithelial neoplasia (CIN), or in situ cervical cancer (CIS)
  • Known hypersensitivity to the study drugs
  • Treatment with any anti-cancer agents within 28 days of study entry
  • Presence of clinically evident active CNS metastases, including leptomeningeal involvement, requiring steroid or radiation therapy
  • Pre-existing peripheral neuropathy (grade 1 or higher)
  • Any other severe concurrent disease which in the judgment of the investigator would make the subject inappropriate for entry into this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01305512

Contacts
Contact: Wen Wee Ma, M.D. (716) 845-3851

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Wen Wee Ma, M.D.    (716) 845-3851      
Principal Investigator: Wen Wee Ma, M.D.         
Sponsors and Collaborators
Sun Pharma Advanced Research Company Limited
Investigators
Principal Investigator: Wen Wee Ma, M.D. Assistant Professor, Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Sun Pharma Advanced Research Company Limited
ClinicalTrials.gov Identifier: NCT01305512     History of Changes
Other Study ID Numbers: CLR_10_28
Study First Received: February 24, 2011
Last Updated: January 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sun Pharma Advanced Research Company Limited:
Solid
Tumor
Taxane

Additional relevant MeSH terms:
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014