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Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma

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ClinicalTrials.gov Identifier: NCT01514188
Recruitment Status : Unknown
Verified September 2013 by CytRx.
Recruitment status was:  Active, not recruiting
First Posted : January 23, 2012
Last Update Posted : September 13, 2013
Sponsor:
Information provided by (Responsible Party):
CytRx

Tracking Information
First Submitted Date  ICMJE January 12, 2012
First Posted Date  ICMJE January 23, 2012
Last Update Posted Date September 13, 2013
Study Start Date  ICMJE December 2011
Estimated Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2012)
Progression-free survival [ Time Frame: Over the duration of the trial, approximately 24 months ]
Progression-free survival (PFS) is defined as the time from enrollment to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2012)
  • Overall Survival [ Time Frame: Approximately 36 months. ]
    Survival is defined as the time from enrollment to date of death. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.
  • Progression-free survival at 4 and 6 months [ Time Frame: Month 4 and 6 ]
  • Objective overall response rate (ORR) [ Time Frame: Approximately 24 months. ]
    The overall tumor response rate is defined as the total proportion of subjects who have an objective tumor response (CR + PR).
  • Safety measures. [ Time Frame: Approximately 24 months. ]
    Adverse events, Ability to remain on assigned treatment (tolerability), Clinical and laboratory data including physical examinations, vital signs, weight, MUGA/cardiac ultrasound evaluations, ECG results and laboratory test results, Use of concomitant medications
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma
Official Title  ICMJE A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma
Brief Summary This is a phase 2b, randomized, open-label, prospective, multicenter study comparing treatment with INNO 206 to doxorubicin in subjects with metastatic, locally advanced, or unresectable soft tissue sarcomas who have not been previously treated with any chemotherapy except potentially as adjuvant or neoadjuvant chemotherapy, and no evidence of tumor recurrence has occurred for at least 12 months.
Detailed Description One hundred five subjects will be enrolled and randomized 2:1 to receive either INNO-206 or doxorubicin. INNO-206 at a dosage of 350 mg/m2 (doxorubicin equivalents of 260 mg/m2) will be administered as a 30 minute IVI on Day 1 of each cycle to approximately 70 subjects. Doxorubicin (75 mg/m2) will be administered to approximately 35 subjects on Day 1 of each cycle. An individual cycle of therapy will be defined as a 3-week (21-day) period. Cycles will be repeated every 3 weeks. Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered. Overall response rates as well as individual categories of response (CR, PR, SD, and PD) will be determined using RECIST 1.1.[28] Time-to-event endpoints, including PFS and OS will be assessed using the Kaplan Meier method.[30] Evaluation of 4- and 6-month progression-free survival will also be performed. Toxicity (adverse events) will be recorded using the NCI CTCAE, version 4.0 (published 28 May 2009).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Soft Tissue Sarcoma
  • Locally Advanced Soft Tissue Sarcoma
  • Unresectable Soft Tissue Sarcoma
Intervention  ICMJE
  • Drug: INNO-206
    INNO-206 administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously (IV) on Day 1 every 21 days for up to 6 consecutive cycles
    Other Name: DOXO-EMCH
  • Drug: Doxorubicin
    Doxorubicin administered at 75 mg/m2 for up to 6 consecutive cycles.
Study Arms  ICMJE
  • Active Comparator: Doxorubicin
    Intervention: Drug: Doxorubicin
  • Experimental: INNO-206
    Intervention: Drug: INNO-206
Publications * Chawla SP, Papai Z, Mukhametshina G, Sankhala K, Vasylyev L, Fedenko A, Khamly K, Ganjoo K, Nagarkar R, Wieland S, Levitt DJ. First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial. JAMA Oncol. 2015 Dec;1(9):1272-80. doi: 10.1001/jamaoncol.2015.3101.

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 19, 2012)
105
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2014
Estimated Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age between 15-80 years (US only), and 18-80 (rest of world (ROW)), male or female.
  • Adjuvant or neoadjuvant chemotherapy (including doxorubicin) allowed if no tumor recurrence for at least 12 months since the last measurement, beginning or end of last chemotherapy.
  • Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic soft tissue sarcoma of intermediate or high grade.
  • Capable of providing informed consent and complying with trial procedures.
  • ECOG performance status 0-2.
  • Life expectancy > 12 weeks.
  • Measurable tumor lesions according to RECIST 1.1 criteria.
  • Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
  • Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
  • Geographic accessibility to the site that ensures the subject will be able to keep all study-related appointments.

Exclusion Criteria:

  • Prior chemotherapy unless for adjuvant or neoadjuvant therapy with no tumor recurrence for at least 12 months.
  • Prior exposure to > 3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
  • Palliative surgery and/or radiation treatment less than 4 weeks prior to Randomization.
  • Exposure to any investigational agent within 30 days of Randomization.
  • Current Stage 1 or 2 soft tissue sarcomas.
  • Current evidence/diagnosis of alveolar soft part sarcoma, chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma, Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, clear cell sarcomas and unresectable low grade liposarcomas.
  • Central nervous system metastasis
  • History of other malignancies except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for > 5 years.
  • Laboratory values: Screening serum creatinine > 1.5x upper limit of normal (ULN), alanine aminotransferase (ALT) > 3 × ULN or >5 × ULN if liver metastases are present, total bilirubin > 3 × ULN, absolute neutrophil count < 1,500/mm3, platelet concentration < 100,000/mm3, hematocrit level < 25% for females or < 27% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > 1.5 × ULN, albumin < 2.0 g/dL.
  • Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines.
  • Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
  • Baseline QTc > 470 msec and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed.
  • History or signs of active coronary artery disease with or without angina pectoris.
  • Serious myocardial dysfunction defined as scintigraphically (e.g. MUGA, myocardial scintigram) or ultrasound determined absolute left ventricular ejection fraction (LVEF) < 45% of predicted.
  • History of HIV infection.
  • Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
  • Major surgery within 3 weeks prior to Randomization.
  • Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
  • Any condition that is unstable and could jeopardize the subject's participation in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 80 Years   (Child, 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 Australia,   Hungary,   India,   Romania,   Russian Federation,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01514188
Other Study ID Numbers  ICMJE INNO-206-P2-STS-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CytRx
Study Sponsor  ICMJE CytRx
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sant Chawla, M.D. Sarcoma Oncology Center
Study Director: Daniel Levitt, M.D., Ph.D. CytRx
PRS Account CytRx
Verification Date September 2013

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