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

Sponsor

CytRx (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01514188

Collaborator

(none)

105

Enrollment

Locations

Arms

Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

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

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 Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered.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

Study Type:

Interventional

Anticipated Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Dec 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2013

Anticipated Study Completion Date :

Apr 1, 2014

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression-free survival [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.

Secondary Outcome Measures

Overall Survival [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 [Month 4 and 6]
Objective overall response rate (ORR) [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. [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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