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

NCT01815294 | Completed Phase 1

• 3 other identifiers: CR100961DOXILNAP10022013-000376-15
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 8

Brief Summary

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

Conditions

Neoplasms; Neoplasms, Ovarian; Neoplasms, Breast; Advanced or Refractory Solid Malignancies

Keywords

Ovarian cancer; Breast cancer; Solid malignancy; Advanced or refractory solid malignancy; Metastatic cancer; DOXIL/CAELYX; Doxorubicin HCL; Bioequivalence

Outcome Measures

Primary Outcomes (3)

• Maximum observed plasma concentration of encapsulated doxorubicin in participants with ovarian cancer

  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

• Area under the plasma-concentration-versus time curve from time 0 to time t of encapsulated doxorubicin in participants with ovarian cancer

  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

• Area under the plasma-concentration-versus time curve from time 0 to infinite time of encapsulated doxorubicin in participants with ovarian cancer

  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

Secondary Outcomes (5)

• Maximum observed plasma concentration of free doxorubicin in participants with solid malignancies

  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

• Area under the plasma-concentration-versus time curve from time 0 to time t of free doxorubicin in participants with solid malignancies

  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

• Area under the plasma-concentration-versus time curve from time 0 to infinite time of free doxorubicin in participants with solid malignancies

  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

• Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)

  Up to 30 days after the last dose of study medication

• Response

  Up to Cycle 3 Day 1

Study Arms (2)

Treatment A: DOXIL/CAELYX (doxorubicin)

EXPERIMENTAL

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; Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA

Treatment B: DOXIL/CAELYX (doxorubicin)

EXPERIMENTAL

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; Drug: DOXIL/CAELYX (doxorubicin) Treatment Sequence BA

Interventions

DOXIL/CAELYX (doxorubicin) Treatment Sequence AB DRUG

Cycle 1 = Treatment A, Cycle 2 = Treatment B

Treatment A: DOXIL/CAELYX (doxorubicin); Treatment B: DOXIL/CAELYX (doxorubicin)

DOXIL/CAELYX (doxorubicin) Treatment Sequence BA DRUG

Cycle 1 = Treatment B, Cycle 2 = Treatment A

Treatment A: DOXIL/CAELYX (doxorubicin); Treatment B: DOXIL/CAELYX (doxorubicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (8)

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Wilrijk, Belgium

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

London, United Kingdom

Location

Related Links

• 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

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Neoplasm Metastasis

Interventions

liposomal doxorubicin; Doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 21, 2013
• Study Start: May 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 4, 2015

Record last verified: 2015-12

Locations

GB (1); BE (2); ES (3); US (2)