A Pivotal Bioequivalence Study of DOXIL/CAELYX (Doxorubicin HCL) in Patients With Advanced or Refractory Solid Malignancies Including Patients With Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01815294
First received: March 14, 2013
Last updated: October 22, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to support the qualification of a replacement manufacturing site for DOXIL/CAELYX (doxorubicin HCL).


Condition Intervention Phase
Neoplasms
Neoplasms, Ovarian
Neoplasms, Breast
Advanced or Refractory Solid Malignancies
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pivotal Bioequivalence Study of DOXIL/CAELYX Manufactured at a New Site in Subjects With Advanced or Refractory Solid Malignancies Including Subjects With Ovarian Cancer.

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Maximum observed plasma concentration of encapsulated doxorubicin in participants with ovarian cancer [ Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-versus time curve from time 0 to time t of encapsulated doxorubicin in participants with ovarian cancer [ Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-versus time curve from time 0 to infinite time of encapsulated doxorubicin in participants with ovarian cancer [ Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum observed plasma concentration of free doxorubicin in participants with solid malignancies [ Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-versus time curve from time 0 to time t of free doxorubicin in participants with solid malignancies [ Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-versus time curve from time 0 to infinite time of free doxorubicin in participants with solid malignancies [ Time Frame: Predose Day 1 Cycles 1-2; Postdose Cycles 1-2 at 15 min, 30 min, 60 min, 90 min, 95 min, 105 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h ] [ Designated as safety issue: No ]
  • Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Response [ Time Frame: Up to Cycle 3 Day 1 ] [ Designated as safety issue: No ]
    Investigator determined response is defined by complete response, partial response or stable disease criteria


Estimated Enrollment: 42
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A: DOXIL/CAELYX (doxorubicin)
50 mg/m2 of doxorubicin manufactured at the current site of manufacturing administered by IV infusion over 90 minutes on Day 1
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
Cycle 1 = Treatment A, Cycle 2 = Treatment B
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Cycle 1 = Treatment B, Cycle 2 = Treatment A
Experimental: Treatment B: DOXIL/CAELYX (doxorubicin)
50 mg/m2 of doxorubicin manufactured at the new site of manufacturing (test product) administered by IV infusion over 90 minutes on Day 1
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence AB
Cycle 1 = Treatment A, Cycle 2 = Treatment B
Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA
Cycle 1 = Treatment B, Cycle 2 = Treatment A

Detailed Description:

This is a randomized (individuals will be assigned in a random order to study treatment sequences), open-label (identity of assigned treatment sequences will be known), single dose, 2-cycle, crossover (patients will receive both treatments in a random order) bioequivalence study of DOXIL/CAELYX (doxorubicin HCL) in patients with advanced or refractory solid malignancies (including patients with ovarian cancer). This study has an adaptive 2-stage design. Bioequivalence based on encapsulated doxorubicin will be tested at the end of Stage 1 using data from at least 24 ovarian cancer patients. An interim analysis of free doxorubicin will be performed at the end of Stage 1 using data from 42 patients of all cancer types. The study may continue into Stage 2 with additional patients of all cancer types; and final evaluation of bioequivalence for free doxorubicin will be performed at the end of Stage 2. The study will include a screening phase followed by an open-label treatment phase consisting of 2 doxorubicin treatment cycles and an end-of-treatment visit on Cycle 3, Day 1. Participants may enter an optional extension phase after 2 cycles. Safety will be monitored throughout the study. Blood samples for pharmacokinetic analysis will be obtained from all participants at specified times over 29 days after starting each study drug administration in Cycles 1 and 2 for determination of plasma concentrations of encapsulated and free doxorubicin.

  Eligibility

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

Inclusion Criteria:

  • Diagnosed with advanced or refractory solid malignancies: histologically or cytologically confirmed advanced ovarian cancer failing platinum-based chemotherapy; histologically or cytologically confirmed metastatic breast cancer after failing approved life-prolonging therapies; any histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, and for which standard treatment is no longer an option
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Recovered from acute toxicity of any prior treatment (exemptions: alopecia, grade-1 neuropathy)
  • Prior doxorubicin (or other anthracyclines) at cumulative dose of <=360 mg/m2 or cumulative epirubicin dose <=720 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 0.3 mg mitoxantrone = 0.25 mg idarubicin)
  • Adequate liver, bone marrow, and renal function according to protocol-defined parameters
  • Left ventricular ejection fraction (LVEF) within normal limits of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography
  • Agrees to protocol-defined use of effective contraception
  • Negative pregnancy test at screening (applicable to women of child bearing potential) within 7 days prior to starting treatment

Exclusion Criteria:

  • Positive history of known brain metastases or leptomeningeal disease (patients with brain metastases can only be enrolled if the following conditions are all met: treated and stable for >4 weeks [>2 weeks after SRS/Cyberknife]; no evidence for progression or hemorrhage after treatment; steroid treatment discontinued at least 2 weeks prior to first administration of doxorubicin; enzyme inducing anti-epileptic drugs discontinued at least 4 weeks before first administration of doxorubicin
  • History of hypersensitivity reaction to doxorubicin HCl or other components of DOXIL/CAELYX
  • Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation allowed >=2 weeks prior to the first dose; >=4 weeks for whole brain radiotherapy); chemotherapy regimens with delayed toxicity within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C); chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks
  • Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of doxorubicin
  • Unstable angina or myocardial infarction within the preceding 12 months; congestive heart failure or any history of uncontrolled cardiac disease >Class II based on New York Heart Association Criteria
  • Has an infection that is either an uncontrolled infection, clinically important (occurred within 4 weeks prior to first dose of study agent), or requiring current systemic intravenous treatment
  • Uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that may potentially impair patient's compliance with study procedures
  • Concomitant use of strong CYP3A4 inhibitors (such as clarithromycin, diltiazem, erythromycin, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin and verapamil) and strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin and St John's wort) from at least 4 weeks before the first dose of doxorubicin in Cycle 1 and until after completion of all pharmacokinetic sampling in Cycle 2
  • Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments
  • Woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
  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: NCT01815294

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
United States, Oklahoma
Withdrawn
Oklahoma City, Oklahoma, United States
United States, Tennessee
Completed
Nashville, Tennessee, United States
United States, Texas
Withdrawn
Houston, Texas, United States
Active, not recruiting
San Antonio, Texas, United States
Belgium
Recruiting
Brussel, Belgium
Recruiting
Wilrijk, Belgium
Canada, Alberta
Withdrawn
Edmonton, Alberta, Canada
Spain
Completed
Barcelona, Spain
Withdrawn
Barcelona, Spain
Withdrawn
Madrid, Spain
Completed
Madrid, Spain
Completed
Sanchinarro, Spain
Completed
Valencia, Spain
United Kingdom
Recruiting
London, United Kingdom
Withdrawn
Surrey, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01815294     History of Changes
Other Study ID Numbers: CR100961, DOXILNAP1002, 2013-000376-15
Study First Received: March 14, 2013
Last Updated: October 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Ovarian cancer
Breast cancer
Solid malignancy
Advanced or refractory solid malignancy
Metastatic cancer
DOXIL/CAELYX
Doxorubicin HCL
Bioequivalence

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Neoplasms by Site
Urogenital Neoplasms
Adnexal Diseases
Breast Diseases
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Ovarian Diseases
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014