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

Phase 2

Completed

Conditions: Metastatic Soft Tissue Sarcoma
Locally Advanced Soft Tissue Sarcoma
Unresectable Soft Tissue Sarcoma

Interventions: Drug: INNO-206
Drug: Doxorubicin

Registration Number: NCT01514188

Lead Sponsor: ImmunityBio, Inc.

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 Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered.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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 126

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
INNO-206	INNO-206	-
Doxorubicin	Doxorubicin	-

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Approximately 24 months	Progression-free survival is defined as the interval from the date of registration (ie, assignment of subject number) to the earliest date of documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first. Progressive Disease is defined as: 20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 new lesion is also considered progression.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-related Toxicities (Adverse Events)	30 days after last dose, up to 136 days (6 cycles of treatment plus 30 days)	Treatment will continue every 21 days until tumor progression is observed, 6 cycles of treatment are completed or unacceptable toxicity occurs.
Progression-free Survival at 4 and 6 Months	Month 4 and 6
Overall Survival	Approximately 35 months	Overall survival was measured from the date of registration (ie, assignment of subject number) to the date of death due to any cause, or the date of last contact.
Objective Overall Response Rate (ORR)	Approximately 24 months	Objective Overall Response will be evaluated using the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1). Changes (i.e., improvements) in tumor measurements from baseline values will be assigned a status of CR or PR. Objective response measurements will comprise the sum of CR plus PR. Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm). Partial Response (PR): 30% decrease in the sum of the longest diameter of target lesions, from the baseline sum longest diameter.

Trial Locations

Locations (32): Vinnytsya Regional Clinical Oncologic Dispensary, Surgical Department
🇺🇦
Vinnytsya, Ukraine
Jehangir Clinical Development Centre Pvt Ltd
🇮🇳
Pune, Maharashtra, India
Christian Medical College
🇮🇳
Vellore, Tami Nadu, India
Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare, Sectia Oncologie
🇷🇴
Baia-Mare, Judet Maramures, Romania
Medisprof SRL
🇷🇴
Cluj-Napoca, Romania
Noble Hospital Clinical Research Department 1st Floor
🇮🇳
Hadapsar, Pune Maharashtra, India
Oncological Institute "Prof. Dr. I. Chiricuta", Cluj-Napoca
🇷🇴
Cluj-Napoca, County Cluj, Romania
Delhi State Cancer Institute
🇮🇳
Pune, Maharashtra, India
Tata Memorial Hospital, Department of Medical Oncology
🇮🇳
Mumbai, India
Clinical County Hospital Mures, Medical Oncology Department
🇷🇴
Targu-Mures, County Mures, Romania
Hemato Oncology Clinic, Vedanta Institute of Medical Science
🇮🇳
Ahmedabad, Gujarat, India
M.S. Ramaiah Medical College and Hospitals
🇮🇳
Bangalore, Karnataka, India
Curie Manavata Cancer Centre
🇮🇳
Nashik, Maharashtra, India
Sarcoma Oncology Center
🇺🇸
Santa Monica, California, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
Royal North Shore
🇦🇺
St. Leonards, New South Wales, Australia
Epworth HealthCare Clinical Trials and Research Centre
🇦🇺
Richmond, Victoria, Australia
Border Medical Oncology
🇦🇺
Wodonga, Victoria, Australia
Royal Hobart Hospital
🇦🇺
Hobart, Australia
Mount Medical Centre
🇦🇺
Perth, Australia
Royal Perth Hospital
🇦🇺
Perth, Australia
State Health Centre Oncology Department
🇭🇺
Budapest, Hungary
The Crown Princess Mary Cancer Centre Westmead
🇦🇺
Sydney, Australia
Blokhin Cancer Research Center
🇷🇺
Moscow, Russian Federation
Municipal institution "Chernivtsi Regional Clinical Oncologic Dispensary",
🇺🇦
Chernivtsi, Ukraine
Stanford University
🇺🇸
Stanford, California, United States
Pennsylvania Hematology Oncology Associates
🇺🇸
Philadelphia, Pennsylvania, United States
CTRC Institute for Drug Development, University of Texas
🇺🇸
San Antonio, Texas, United States
State Healthcare Institution "Republican Clinical Oncological Center of the Ministry of Health of Republic of Tatarstan"
🇷🇺
Kazan, Republic Of Tatarstan, Russian Federation
Municipal Institution "Dnipropetrovsk City Multi-Field Clinical Hospital #4" of Dnipropetrovsk Regional Councel
🇺🇦
Dnipropetrovsk, Ukraine
Lviv State Oncological Regional Treatment - Diagnostics Center, Chemotherapy Department
🇺🇦
Lviv, Ukraine
State Institution "Institute of Medical Radiology named after S.P.Grygoryev of National Academy of Medical Sciences of Ukraine",
🇺🇦
Kharkiv, Ukraine