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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CytRx
ClinicalTrials.gov Identifier:
NCT01514188
First received: January 12, 2012
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Soft Tissue Sarcoma
Locally Advanced Soft Tissue Sarcoma
Unresectable Soft Tissue Sarcoma
Drug: INNO-206
Drug: Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CytRx:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Over the duration of the trial, approximately 24 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Approximately 36 months. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Objective overall response rate (ORR) [ Time Frame: Approximately 24 months. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 105
Study Start Date: December 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Doxorubicin Drug: Doxorubicin
Doxorubicin administered at 75 mg/m2 for up to 6 consecutive cycles.
Experimental: INNO-206 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

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).

  Eligibility

Ages Eligible for Study:   15 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01514188

  Show 34 Study Locations
Sponsors and Collaborators
CytRx
Investigators
Principal Investigator: Sant Chawla, M.D. Sarcoma Oncology Center
Study Director: Daniel Levitt, M.D., Ph.D. CytRx
  More Information

No publications provided

Responsible Party: CytRx
ClinicalTrials.gov Identifier: NCT01514188     History of Changes
Other Study ID Numbers: INNO-206-P2-STS-01
Study First Received: January 12, 2012
Last Updated: September 12, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
India: Drugs Controller General of India
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Hungary: Ministry of Health, Social and Family Affairs
Romania: National Medicines Agency

Keywords provided by CytRx:
sarcoma
soft-tissue sarcoma
Metastatic,locally advanced, or unresectable soft tissue sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014