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

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

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.

Study Overview

• Status: Unknown
• Conditions: Unresectable Soft Tissue Sarcoma; Metastatic Soft Tissue Sarcoma; Locally Advanced Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Doxorubicin; Drug: INNO-206

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 Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered.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: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Hobart, Australia
    • Royal Hobart Hospital
  • Perth, Australia, 6000
    • Royal Perth Hospital
  • Perth, Australia
    • Mount Medical Centre
  • Sydney, Australia, 2145
    • The Crown Princess Mary Cancer Centre Westmead
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore
  • Victoria
    • Richmond, Victoria, Australia
      • Epworth HealthCare Clinical Trials and Research Centre
    • Wodonga, Victoria, Australia, 3690
      • Border Medical Oncology
• Hungary
  • Budapest, Hungary
    • State Health Centre Oncology Department
• India
  • Mumbai, India, 400012
    • Tata Memorial Hospital, Department of Medical Oncology
  • Ahmedaba
    • Navrangpura, Ahmedaba, India, 380009
      • Hemato Oncology Clinic, Vedanta Institute of Medical Science
  • Delhi
    • Dilshad Garden, Delhi, India, 110095
      • Delhi State Cancer Institute
  • Gujarat
    • Navrangpura Ahmedabad, Gujarat, India, 380009
      • Hemato Oncology Clinic, Vedanta Institute of Medical Science
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • M.S. Ramaiah Medical College and Hospitals
  • Maharashtra
    • Nashik, Maharashtra, India, 422101
      • Curie Manavata Cancer Centre
    • Pune, Maharashtra, India, 411001
      • Delhi State Cancer Institute
    • Pune, Maharashtra, India, 411001
      • Jehangir Clinical Development Centre Pvt Ltd
  • Pune Maharashtra
    • Hadapsar, Pune Maharashtra, India, 411013
      • Noble Hospital Clinical Research Department 1st Floor
  • Tami Nadu
    • Vellore, Tami Nadu, India, 532004
      • Christian Medical College
• Romania
  • Cluj-Napoca, Romania
    • Medisprof SRL
  • County Cluj
    • Cluj-Napoca, County Cluj, Romania, 400015
      • Oncological Institute "Prof. Dr. I. Chiricuta", Cluj-Napoca
  • County Mures
    • Targu-Mures, County Mures, Romania, 540141
      • Clinical County Hospital Mures, Medical Oncology Department
  • Judet Maramures
    • Baia-Mare, Judet Maramures, Romania, 430031
      • Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare, Sectia Oncologie
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center
  • Republic of Tatarstan
    • Kazan, Republic of Tatarstan, Russian Federation, 420029
      • State Healthcare Institution "Republican Clinical Oncological Center of the Ministry of Health of Republic of Tatarstan"
• Ukraine
  • Chernivtsi, Ukraine, 58013
    • Municipal institution "Chernivtsi Regional Clinical Oncologic Dispensary",
  • Dnipropetrovsk, Ukraine, 49102
    • Municipal Institution "Dnipropetrovsk City Multi-Field Clinical Hospital #4" of Dnipropetrovsk Regional Councel
  • Kharliv, Ukraine, 61024
    • State Institution "Institute of Medical Radiology named after S.P.Grygoryev of National Academy of Medical Sciences of Ukraine",
  • Lviv, Ukraine, 79031
    • Lviv State Oncological Regional Treatment - Diagnostics Center, Chemotherapy Department
  • Vinnytsya, Ukraine, 21029
    • Vinnytsya Regional Clinical Oncologic Dispensary, Surgical Department
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Hematology Oncology Associates
  • Texas
    • San Antonio, Texas, United States, 78229-3900
      • CTRC Institute for Drug Development, University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: DOXO-EMCH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	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.	Over the duration of the trial, approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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.	Approximately 36 months.
Progression-free survival at 4 and 6 months		Month 4 and 6
Objective overall response rate (ORR)	The overall tumor response rate is defined as the total proportion of subjects who have an objective tumor response (CR + PR).	Approximately 24 months.
Safety measures.	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	Approximately 24 months.

Collaborators and Investigators

• Sponsor: CytRx
• Investigators: Principal Investigator: Sant Chawla, M.D., Sarcoma Oncology Center

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): April 1, 2014

Study Registration Dates

• First Submitted: January 12, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (Estimate): January 23, 2012

Study Record Updates

• Last Update Posted (Estimate): September 13, 2013
• Last Update Submitted That Met QC Criteria: September 12, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: soft-tissue sarcoma; sarcoma; Metastatic,locally advanced, or unresectable soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: INNO-206-P2-STS-01