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

Metastatic Soft Tissue Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01514188
• Other study ID #: INNO-206-P2-STS-01
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 12, 2012
• Last updated: September 12, 2013
• Start date: December 2011
• Est. completion date: April 2014

Study information

• Verified date: September 2013
• Source: CytRx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationIndia: Drugs Controller General of IndiaRussia: Ministry of Health of the Russian FederationUkraine: Ministry of HealthHungary: Ministry of Health, Social and Family AffairsRomania: National Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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 Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered.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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: April 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Locally Advanced Soft Tissue Sarcoma
• Metastatic Soft Tissue Sarcoma
• Sarcoma
• Unresectable Soft Tissue Sarcoma

Intervention

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
• Doxorubicin
Doxorubicin administered at 75 mg/m2 for up to 6 consecutive cycles.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
CytRx

Countries where clinical trial is conducted

United States,  Australia,  Hungary,  India,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	Progression-free survival at 4 and 6 months		Month 4 and 6	No
Secondary	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.	No
Secondary	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.	Yes