Clinical trial NCT01514188: Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Soft Tissue Sarcoma
Locally Advanced Soft Tissue Sarcoma
Unresectable Soft Tissue Sarcoma
Keywords: sarcoma
soft-tissue sarcoma
Metastatic,locally advanced, or unresectable soft tissue sarcoma
Lead sponsor: ImmunityBio, Inc.
Sponsor class: INDUSTRY
First posted: 2012-01-23
Enrollment: 126
Sex: ALL
Minimum age (years): 15
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered.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

Eligibility 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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Approximately 35 months
measure: Progression-free Survival at 4 and 6 Months
timeFrame: Month 4 and 6
measure: Objective Overall Response Rate (ORR)
timeFrame: Approximately 24 months
measure: Number of Participants With Treatment-related Toxicities (Adverse Events)
timeFrame: 30 days after last dose, up to 136 days (6 cycles of treatment plus 30 days)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Philadelphia
country: United States
facility: Pennsylvania Hematology Oncology Associates
state: Pennsylvania
city: San Antonio
country: United States
facility: CTRC Institute for Drug Development, University of Texas
state: Texas
city: St. Leonards
country: Australia
facility: Royal North Shore
state: New South Wales
city: Richmond
country: Australia
facility: Epworth HealthCare Clinical Trials and Research Centre
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: Victoria
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Perth
country: Australia
facility: Mount Medical Centre
city: Sydney
country: Australia
facility: The Crown Princess Mary Cancer Centre Westmead
city: Budapest
country: Hungary
facility: State Health Centre Oncology Department
city: Thaltej
country: India
facility: Hemato Oncology Clinic, Vedanta Institute of Medical Science
state: Ahmedaba
city: Mandoli
country: India
facility: Delhi State Cancer Institute
state: Delhi
city: Ahmedabad
country: India
facility: Hemato Oncology Clinic, Vedanta Institute of Medical Science
state: Gujarat
city: Bangalore
country: India
facility: M.S. Ramaiah Medical College and Hospitals
state: Karnataka
city: Nashik
country: India
facility: Curie Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Delhi State Cancer Institute
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre Pvt Ltd
state: Maharashtra
city: Hadapsar
country: India
facility: Noble Hospital Clinical Research Department 1st Floor
state: Pune Maharashtra
city: Vellore
country: India
facility: Christian Medical College
state: Tami Nadu
city: Mumbai
country: India
facility: Tata Memorial Hospital, Department of Medical Oncology
city: Cluj-Napoca
country: Romania
facility: Oncological Institute "Prof. Dr. I. Chiricuta", Cluj-Napoca
state: County Cluj
city: Targu-Mures
country: Romania
facility: Clinical County Hospital Mures, Medical Oncology Department
state: County Mures
city: Baia-Mare
country: Romania
facility: Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare, Sectia Oncologie
state: Judet Maramures
city: Cluj-Napoca
country: Romania
facility: Medisprof SRL
city: Kazan
country: Russian Federation
facility: State Healthcare Institution "Republican Clinical Oncological Center of the Ministry of Health of Republic of Tatarstan"
state: Republic Of Tatarstan
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
city: Chernivtsi
country: Ukraine
facility: Municipal institution "Chernivtsi Regional Clinical Oncologic Dispensary",
city: Dnipropetrovsk
country: Ukraine
facility: Municipal Institution "Dnipropetrovsk City Multi-Field Clinical Hospital #4" of Dnipropetrovsk Regional Councel
city: Kharkiv
country: Ukraine
facility: State Institution "Institute of Medical Radiology named after S.P.Grygoryev of National Academy of Medical Sciences of Ukraine",
city: Lviv
country: Ukraine
facility: Lviv State Oncological Regional Treatment - Diagnostics Center, Chemotherapy Department
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Clinical Oncologic Dispensary, Surgical Department
Study officials:
affiliation: Sarcoma Oncology Center
name: Sant Chawla, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: CytRx
name: Daniel Levitt, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.