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PCI-24781 in Combination With Doxorubicin to Treat Sarcoma

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ClinicalTrials.gov Identifier: NCT01027910
Recruitment Status : Completed
First Posted : December 9, 2009
Results First Posted : February 14, 2017
Last Update Posted : February 14, 2017
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Pharmacyclics LLC.
Information provided by (Responsible Party):
Edwin Choy, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE December 8, 2009
First Posted Date  ICMJE December 9, 2009
Results First Submitted Date  ICMJE March 9, 2016
Results First Posted Date  ICMJE February 14, 2017
Last Update Posted Date February 14, 2017
Study Start Date  ICMJE February 2009
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2016)
Maximum Tolerated Dose [ Time Frame: up to 30 days after starting study drugs ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2009)
  • Phase I: To determine the MTD (and/or recommended phase II dose) of PCI-24781 when given orally twice a daily for 5 days in combination with doxorubicin. [ Time Frame: 1 year ]
  • Phase II: To assess the response rate of PCI-24781 at the MTD when given with doxorubicin in patients whose disease has failed to be controlled despite prior therapy. [ Time Frame: 2 years ]
Change History Complete list of historical versions of study NCT01027910 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2016)
  • Dose Limiting Toxicities [ Time Frame: 1 year ]
    number of patients who experienced dose limiting toxicities
  • Number of Partial Responses (PR) [ Time Frame: 1 year ]
    number of patients who demonstrated partial response to therapy as determined by RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
  • Rate of Progression-free Survival at 6 Months in Participants Who Received PCI-24781/Doxorubicin Combination Administration. [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2009)
  • Phase I: To evaluate the safety and tolerability of PCI-24781 in combination with doxorubicin. [ Time Frame: 1 year ]
  • Phase I: To determine the pharmacokinetic and pharmacodynamic parameters of PCI-24781 in combination with doxorubicin in sarcoma patients. [ Time Frame: 1 year ]
  • Phase I: To measure evidence of antitumor activity of PCI-24781 in combination with doxorubicin in this patient population. [ Time Frame: 1 year ]
  • Phase II: Assess the duration of response and rate of progression-free survival at 6 months in participants who received PCI-24781/doxorubicin combination administration. [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PCI-24781 in Combination With Doxorubicin to Treat Sarcoma
Official Title  ICMJE Phase I/II Study of PCI-24781 in Combination With Doxorubicin for Treatment of Advanced Sarcomas Following Failure or Prior Anthracycline Therapy
Brief Summary The purpose of this research study is to determine the safety and maximum tolerated dose of PCI-24781 that can be given safely with doxorubicin (phase I) and the safety and efficacy of PCI-24781 when used in combination with doxorubicin (phase II) in patients with advanced sarcomas. The study drug, PCI-24781, is believed to regulate genes involved in tumor cell growth. The other study drug, doxorubicin, is considered a standard chemotherapeutic treatment for advanced sarcoma patients. We hypothesize that combining PCI-24781 with doxorubicin can overcome chemoresistance to doxorubicin.
Detailed Description
  • In the phase I portion of the study, since we are looking for the highest dose of PCI-24781 that can be administered safely without severe or unmanageable side effects in participants that have advanced sarcoma, not everyone who participates in this research study will receive the same dose of PCI-24871.
  • Each treatment cycle is 3 weeks (21 days). Participants will take capsules of PCI-24871 for five consecutive days starting on Day 1 of each 3 week cycle. On Day 4 of each cycle, participants will come to the clinic to receive doxorubicin intravenously.
  • At specific time intervals, participants will return to the clinic for the following tests and procedures: physical examination, vital signs, blood tests, urine test, EKG, assessment of the tumor by CT scan, and an ECHO or MUGA.
  • Participants may remain on the study for a maximum of 6 cycles (about 4-5 months). After the last cycle, as long as the participant is showing benefit, they may elect to continue taking PCI-24781 alone, in which case they will continue in this research study until there is evidence of their tumor growing.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sarcoma
Intervention  ICMJE
  • Drug: PCI-24781
    Capsules taken orally for 5 consecutive days starting on Day 1 of each 3 week cycle
    Other Name: PCI24781
  • Drug: Doxorubicin
    Administered intravenously on Day 4 of each 3 week cycle
    Other Name: Adriamycin
  • Drug: GCSF
    Administered on Day 5 of each 3 weeks cycle in Arm 1 if determined to be clinically indicated, and in all patients enrolled into Arm 2
    Other Name: Neupogen
Study Arms  ICMJE
  • Experimental: PCI-24781 without mandated GCSF
    PCI-24781 in combination with doxorubicin without mandated GCSF
    Interventions:
    • Drug: PCI-24781
    • Drug: Doxorubicin
    • Drug: GCSF
  • Experimental: PCI-24781 with mandated GCSF
    PCI-24781 in combination with doxorubicin with mandated GCSF
    Interventions:
    • Drug: PCI-24781
    • Drug: Doxorubicin
    • Drug: GCSF
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 21, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2009)
47
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants must have histologically confirmed metastatic or unresectable sarcoma
  • All participants must have received no more than a lifetime cumulative maximum dose of 300 mg/m2 or less of prior doxorubicin and no other anthracycline therapy.
  • Participants must have measurable disease, defined as at least one unirradiated lesion that can be accurately measured in at least one dimension as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan.
  • ECOG performance status of 2 or less
  • Ability to swallow oral capsules without difficulty
  • Participants must have normal organ and marrow function as outlined in the protocol.
  • Women of childbearing potential must have a negative serum/urine pregnancy test within 7 days prior to receiving the first dose of PCI-24781.
  • An ECHO or MUGA demonstrating EF > 50% is required within 4 weeks prior to study drug administration.
  • 18 years of age or older

Exclusion Criteria:

  • Participants who have had immunotherapy, chemotherapy, experimental therapy or radiotherapy within 4 weeks before first day of study drug dosing or those who have not recovered to grade 1 or baseline from adverse events due to agents administered more than 4 weeks earlier.
  • Participants who have previously received > 300 mg/m2 cumulative lifetime dose of doxorubicin, or who have received any other anthracycline chemotherapy.
  • Major surgery within 4 weeks before first day of study drug dosing
  • Participants with known central nervous system/brain metastases
  • Participants receiving chronic corticosteroids > 20 mg prednisone equivalent per day for > 7 consecutive days (Topical, inhaled or nasal corticosteroids are permitted).
  • Participants with any documented malabsorption syndromes or other conditions that may impair the absorption of PCI-24781 capsules.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Participants requiring concurrent therapeutic anticoagulation or have received therapeutic anticoagulation within 2 weeks of the first day of dosing.
  • Risk factors for Torsades de Pointes, or use, within 4 weeks of starting study drug administration, of medications known to prolong QTc interval or that may be associated with Torsades de Pointes.
  • QTc prolongation or other significant ECG abnormalities defined as 2nd degree AV block type II, 3rd degree AV block, or bradycardia.
  • History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or coronary artery stenting within the past 6 months.
  • For patients with history of major coronary artery disease in the judgement of the responsible physician, a cardiac stress test that demonstrates clinically significant abnormalities when performed within 28 days of first dose of study drug
  • Pregnant or breastfeeding women
  • Women of childbearing potential, or sexually active men unwilling to use adequate contraceptive protection during the course of the study
  • HIV-positive individuals
  • Other medical or psychiatric illness or organ dysfunction that, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of PCI-24781
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01027910
Other Study ID Numbers  ICMJE 09-352
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Edwin Choy, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE
  • Dana-Farber Cancer Institute
  • Brigham and Women's Hospital
  • Pharmacyclics LLC.
Investigators  ICMJE
Principal Investigator: Edwin Choy, MD, PhD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP