Phase 3 Study to Treat Patients With Soft Tissue Sarcomas
- Conditions
- Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma
- Interventions
- Drug: Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)
- Registration Number
- NCT02049905
- Lead Sponsor
- ImmunityBio, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 433
- Has provided written informed consent prior to any study related activities.
- Age ≥15 years (US only), and 18-80 (rest of world (ROW)), male or female.
- 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.
- 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.
- 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.
- 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.
- Capable of providing informed consent and complying with trial procedures.
- ECOG PS 0-2.
- Life expectancy >12 weeks.
- Measurable tumor lesions according to RECIST 1.1 criteria.[50]
- 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.)
- 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.
- Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
- Accessibility to the site that optimizes the subject's ability to keep all study-related appointments.
- Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin.
- Palliative surgery and/or radiation treatment within 30 days prior to date of randomization.
- Exposure to any investigational agent within 30 days of date of randomization.
- Exposure to any systemic chemotherapy within 30 days of date of randomization.
- An inadequate tumor specimen as defined by the central pathologist.
- 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.
- Evidence of central nervous system (CNS) metastasis who have not received prior definitive therapy for their lesions.
- 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.
- 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.
- Clinically evident congestive heart failure (CHF) > 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 within the last 6 months.
- Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) below the institution's lower limit of predicted normal.
- Known history of HIV infection.
- Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. The Medical Monitor should be contacted for any uncertainties.
- Major surgery within 30 days prior to date of randomization.
- 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.
- 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 Aldoxorubicin Aldoxorubicin Aldoxorubicin is administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously on Day 1 every 21-day cycles until tumor progression or unacceptable toxicity occurs. Investigator's Choice of Treatment Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide) These treatments include: 1. Dacarbazine administered at 1000 mg/m2 by intravenous infusion (IVI), over 90±15 minutes on Day 1 every 21 days until tumor progression or unacceptable toxicity occurs; 2. Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 3. Gemcitabine, 900 mg/m2 by IVI over 90 minutes on Days 1 and 8, plus docetaxel, 100 mg/m2 by IVI over 1 hour on Day 8 of a 28 day cycle until tumor progression or unacceptable toxicity occurs; 4. Doxorubicin, 75 mg/m2 by IVI over 5 to 30 minutes every 21 days for a maximum cumulative dose of 550 mg/m2 or unacceptable toxicity occurs; or 5. Ifosfamide 2.0 g/m2 administered over 2 to 4 hours on Days 1-4 of a 21 day cycle + mesna per standard site administration regimen until tumor progression or unacceptable toxicity occurs.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 24 months PFS is defined as the time from the date of randomization to first documentation of objective tumor progression, according to RECIST 1.1 Criteria, or to death due to any cause in the absence of previous documentation of objective tumor progression. For subjects without documentation of objective tumor progression, who started other anti-tumor treatment, or lost to follow up/withdrew consent prior to confirmed progression, PFS is censored at the date of the last tumor assessment.
PFS is defined as the interval from the date of randomization to the earliest date of documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first.
PD 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 PD.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (73)
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Navarra, Spain
The James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
U of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Leiden Universitair Medisch Centrum
🇳🇱Leiden, Zuid-Holland, Netherlands
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Oncology Associates, PC
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Center for Health and Healing
🇺🇸Portland, Oregon, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Samuel Oschin Cancer Center
🇺🇸Los Angeles, California, United States
Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
Kansas City Cancer Center
🇺🇸Overland Park, Kansas, United States
Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Oncology Specialists, SC
🇺🇸Niles, Illinois, United States
Institut Bergonie
🇫🇷Bordeaux Cedex, Aquitaine, France
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Centre Georges Francois Leclerc
🇫🇷Dijon, Bourgogne, France
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
City of Hope Medical Group
🇺🇸Duarte, California, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
City Oncology Hospital #2
🇷🇺Moscow, Russian Federation
IRCCS Instituto Ortopedico Rizzoli
🇮🇹Bologna, Italy
Sharet Institute of Oncology Hadassah Ein Karem Medical Center
🇮🇱Jerusalem, Israel
Herlev Hospital
🇩🇰Herlev, Denmark
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Edward Cancer Center
🇺🇸Naperville, Illinois, United States
Centre Hospitalier Regional et Universitaire - Hospital Bretonneau
🇫🇷Tours, Centre-Val-de-Loire, France
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Hospital Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hopital Rene Huguenin - Institut Curie
🇫🇷Saint-Cloud, Ile-de-France, France
Institut Gustave Roussy
🇫🇷Villejuif, Ile-de-France, France
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Washington University
🇺🇸Saint Louis, Missouri, United States
Royal North Shore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
U of CO Health Sciences Center
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Juravinski Cancer Center
🇨🇦Hamilton, Ontario, Canada
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Jefferson Medical College
🇺🇸Philadelphia, Pennsylvania, United States
The University of Arizona
🇺🇸Tucson, Arizona, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Centre Leon Berard
🇫🇷Lyon, Rhone-Alpes, France
McGill University
🇨🇦Montreal, Quebec, Canada
Fondazione del Piemonte per l'Oncologia
🇮🇹Candiolo, Torino, Italy
Azienda Ospedaliero-Universitaria di Bologna-Policlinico S Orsola-Malpighi
🇮🇹Bologna, Italy
Instytut im.Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Istituto Europeo di Oncologia Milano
🇮🇹Milano, Italy
Istituto Oncologico Veneto
🇮🇹Padova, Italy
State Institution "Blokhin Cancer Research Centre RAMS"
🇷🇺Moscow, Russian Federation
Hospital Universitario Son Espases
🇪🇸Palma de Mallorca, Baleares, Spain
Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan
🇷🇺Tatarstan, Russian Federation
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castellón de la Plana, Castellon, Spain
Inst Catala D'Oncologia
🇪🇸Barcelona, Spain
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro
🇪🇸Madrid, Spain
Hospital San Carlos Madrid
🇪🇸Madrid, Spain
Rambam Medical Center
🇮🇱Haifa, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Instituto Clinico Oncologica del Sur (ICOS)
🇨🇱Temuco, Araucanía, Chile
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Magyar Honvedseg Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary