Clinical trial NCT02049905: Phase 3 Study to Treat Patients With Soft Tissue Sarcomas
Official title: A Multicenter, Randomized, Open-Label Phase 3 Study to Investigate the Efficacy and Safety of Aldoxorubicin Compared to Investigator's Choice in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcomas Who Either Relapsed or Were Refractory to Prior Non-Adjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma
Keywords: soft tissue sarcoma
unresectable
metastatic
locally advanced
sarcoma
Lead sponsor: ImmunityBio, Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-30
Enrollment: 433
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of aldoxorubicin in subjects with metastatic, locally advanced, or unresectable soft tissue sarcomas.


Eligibility criteria: Inclusion Criteria:

1. Has provided written informed consent prior to any study related activities.
2. Age ≥15 years (US only), and 18-80 (rest of world (ROW)), male or female.
3. Histological confirmation of intermediate or high grade soft-tissue sarcoma. Tissue must be sent to a central pathology lab for review but will not preclude entry onto the study. Final assignment of tumor grade and histology will be based on the designation provided by the central pathology review.
4. An adequate tumor specimen obtained by either excisional biopsy, incisional biopsy or core needle biopsy must be sent to the central pathology lab for evaluation. The material must measure at least 0.8 × 0.1 cm in size or contain at least 50 tumor cells.
5. Locally advanced, unresectable, and/or metastatic soft-tissue sarcoma of intermediate or high grade with evidence of disease progression by either computed tomography (CT) or magnetic resonance imaging (MRI) scan, or clinical judgment on or after the last cancer therapy within 6 months prior to randomization.
6. Relapsed or refractory (lack of response) to ≥1 course of systemic therapy regimen(s), excluding adjuvant or neoadjuvant chemotherapy, and is incurable by either surgery or radiation.
7. Capable of providing informed consent and complying with trial procedures.
8. ECOG PS 0-2.
9. Life expectancy \>12 weeks.
10. Measurable tumor lesions according to RECIST 1.1 criteria.\[50\]
11. 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.)
12. Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (see Inclusion 11 plus condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and agree to continue use for 6 months after the final dose of study treatment.
13. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
14. Accessibility to the site that optimizes the subject's ability to keep all study-related appointments.

Exclusion Criteria:

1. Prior exposure to \>375 mg/m2 of doxorubicin or liposomal doxorubicin.
2. Palliative surgery and/or radiation treatment within 30 days prior to date of randomization.
3. Exposure to any investigational agent within 30 days of date of randomization.
4. Exposure to any systemic chemotherapy within 30 days of date of randomization.
5. An inadequate tumor specimen as defined by the central pathologist.
6. Current evidence/diagnosis of alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma (unless transformed to fibrosarcoma), Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, clear cell sarcomas.
7. Evidence of central nervous system (CNS) metastasis who have not received prior definitive therapy for their lesions.
8. History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for ≥5 years.
9. Laboratory values: Screening serum creatinine \>1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) \>3×ULN or \>5×ULN if liver metastases are present, total bilirubin \>2×ULN, absolute neutrophil count (ANC) \<1,500/mm3, platelet concentration \<100,000/mm3, hemoglobin \<9g/dL.
10. Clinically evident congestive heart failure (CHF) \> class II of the New York Heart Association (NYHA) guidelines.
11. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
12. Baseline QTc \>470 msec and/or previous history of QT prolongation while taking other medications.
13. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed.
14. History or signs of active coronary artery disease with or without angina pectoris within the last 6 months.
15. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) below the institution's lower limit of predicted normal.
16. Known history of HIV infection.
17. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. The Medical Monitor should be contacted for any uncertainties.
18. Major surgery within 30 days prior to date of randomization.
19. Current or past substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
20. Any condition that is unstable and could jeopardize the subject's participation in the study.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Group
state: California
city: Los Angeles
country: United States
facility: Samuel Oschin Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: U of CO Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Naperville
country: United States
facility: Edward Cancer Center
state: Illinois
city: Niles
country: United States
facility: Oncology Specialists, SC
state: Illinois
city: Overland Park
country: United States
facility: Kansas City Cancer Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute
state: Ohio
city: Portland
country: United States
facility: Center for Health and Healing
state: Oregon
city: Philadelphia
country: United States
facility: Jefferson Medical College
state: Pennsylvania
city: Pittsburgh
country: United States
facility: U of Pittsburgh Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Temuco
country: Chile
facility: Instituto Clinico Oncologica del Sur (ICOS)
state: Araucanía
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Bordeaux Cedex
country: France
facility: Institut Bergonie
state: Aquitaine
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
state: Bourgogne
city: Tours
country: France
facility: Centre Hospitalier Regional et Universitaire - Hospital Bretonneau
state: Centre-Val-de-Loire
city: Saint-Cloud
country: France
facility: Hopital Rene Huguenin - Institut Curie
state: Ile-de-France
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Ile-de-France
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhone-Alpes
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Sharet Institute of Oncology Hadassah Ein Karem Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia
state: Torino
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna-Policlinico S Orsola-Malpighi
city: Bologna
country: Italy
facility: IRCCS Instituto Ortopedico Rizzoli
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia Milano
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
state: Zuid-Holland
city: Warszawa
country: Poland
facility: Instytut im.Marii Sklodowskiej-Curie
city: Moscow
country: Russian Federation
facility: State Institution "Blokhin Cancer Research Centre RAMS"
city: Moscow
country: Russian Federation
facility: City Oncology Hospital #2
city: Tatarstan
country: Russian Federation
facility: Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Baleares
city: Castellón de la Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
state: Castellon
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
state: Madrid
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Inst Catala D'Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro
city: Madrid
country: Spain
facility: Hospital San Carlos Madrid
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References: