Phase 3 Study to Treat Patients With Soft Tissue Sarcomas

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified May 2017 by ImmunityBio, Inc.
Sponsor
ImmunityBio, Inc.
Information Provided by (Responsible Party)
ImmunityBio, Inc.
Clinicaltrials.gov Identifier
NCT02049905
Other Study ID Numbers:
ALDOXORUBICIN-P3-STS-01
First Submitted
January 27, 2014
First Posted
January 29, 2014
Results First Posted
April 4, 2024
Last Update Posted
June 12, 2024
Last Verified
May 2017

ClinicalTrials.gov processed this data on June 2024. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma
Drug: AldoxorubicinDrug: Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)

Study Design

Study TypeInterventional
Actual Enrollment433 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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 Start DateDecember 31, 2013
Actual Primary Completion DateApril 30, 2017
Actual Study Completion DateApril 30, 2017

Groups and Cohorts

Group/CohortIntervention/Treatment
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.
Drug: Aldoxorubicin
Investigator's Choice of Treatment
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.
Drug: Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)

Outcome Measures

Primary Outcome Measures
  1. Progression-Free Survival (PFS)
    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.

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsImmunityBio, Inc.
Locations
University of Alabama at Birmingham | Birmingham Alabama, United States, 35243Arizona Oncology Associates, PC | Phoenix Arizona, United States, 85016The University of Arizona | Tucson Arizona, United States, 85719City of Hope Medical Group | Duarte California, United States, 91010Samuel Oschin Cancer Center | Los Angeles California, United States, 90048UCLA Medical Center | Los Angeles California, United States, 90095Sarcoma Oncology Center | Santa Monica California, United States, 940403Stanford University Medical Center | Stanford California, United States, 94305U of CO Health Sciences Center | Aurora Colorado, United States, 80045Rocky Mountain Cancer Centers | Denver Colorado, United States, 80218Mayo Clinic | Jacksonville Florida, United States, 32224Moffitt Cancer Center | Tampa Florida, United States, 33612Georgia Cancer Specialists | Atlanta Georgia, United States, 30341Northwestern Medical Faculty Foundation | Chicago Illinois, United States, 60611Edward Cancer Center | Naperville Illinois, United States, 60540Oncology Specialists, SC | Niles Illinois, United States, 60714Kansas City Cancer Center | Overland Park Kansas, United States, 66210Massachusetts General Hospital | Boston Massachusetts, United States, 02114Dana Farber Cancer Institute | Boston Massachusetts, United States, 02115University of Michigan | Ann Arbor Michigan, United States, 48109University of Minnesota | Minneapolis Minnesota, United States, 55455Mayo Clinic | Rochester Minnesota, United States, 55905Washington University | St Louis Missouri, United States, 63110Nebraska Methodist Hospital | Omaha Nebraska, United States, 68114Roswell Park Cancer Institute | Buffalo New York, United States, 14263Levine Cancer Institute | Charlotte North Carolina, United States, 28204Wake Forest University Baptist Medical Center | Winston-Salem North Carolina, United States, 27157University Hospitals Case Medical Center | Cleveland Ohio, United States, 44106Cleveland Clinic | Cleveland Ohio, United States, 44195The James Cancer Hospital and Solove Research Institute | Columbus Ohio, United States, 43202Center for Health and Healing | Portland Oregon, United States, 97239Jefferson Medical College | Philadelphia Pennsylvania, United States, 19107U of Pittsburgh Cancer Institute | Pittsburgh Pennsylvania, United States, 15232Vanderbilt University | Nashville Tennessee, United States, 37212Fletcher Allen Health Care | Burlington Vermont, United States, 05405Medical College of Wisconsin | Milwaukee Wisconsin, United States, 53226Royal North Shore Hospital | Saint Leonards New South Wales, Australia, Westmead Hospital | Westmead New South Wales, Australia, Cross Cancer Institute | Edmonton Alberta, Canada, Juravinski Cancer Center | Hamilton Ontario, Canada, LBV5C2McGill University | Montreal Quebec, Canada, H2W156Instituto Clinico Oncologica del Sur (ICOS) | Temuco Araucania, Chile, Herlev Hospital | Herlev , Denmark, 2730Institut Bergonie | Bordeaux Aquitaine, France, Centre Leon Berard | Lyon Auvergne-Rhône-Alpes, France, Centre Georges Francois Leclerc | Dijon Bourgogne-Franche-Comté, France, Centre Hospitalier Regional et Universitaire - Hospital Bretonneau | Tours Centre-Val de Loire, France, Hopital Rene Huguenin - Institut Curie | Saint-Cloud Île-de-France Region, France, Institut Gustave Roussy | Villejuif Île-de-France Region, France, 94800Magyar Honvedseg Egeszsegugyi Kozpont | Budapest , Hungary, Rambam Medical Center | Haifa , Israel, Sharet Institute of Oncology Hadassah Ein Karem Medical Center | Jerusalem , Israel, Chaim Sheba Medical Center | Ramat Gan , Israel, Tel Aviv Sourasky Medical Center | Tel Aviv , Israel, Fondazione del Piemonte per l'Oncologia | Candiolo Torino, Italy, Azienda Ospedaliero-Universitaria di Bologna-Policlinico S Orsola-Malpighi | Bologna , Italy, IRCCS Instituto Ortopedico Rizzoli | Bologna , Italy, Istituto Europeo di Oncologia Milano | Milan , Italy, 20141Istituto Oncologico Veneto | Padova , Italy, 35128Leiden Universitair Medisch Centrum | Leiden South Holland, Netherlands, 2333ZAInstytut im.Marii Sklodowskiej-Curie | Warsaw , Poland, State Institution "Blokhin Cancer Research Centre RAMS" | Moscow , Russia, 115478City Oncology Hospital #2 | Moscow , Russia, 143423Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan | Tatarstan , Russia, 420029Hospital Universitario Son Espases | Palma de Mallorca Balearic Islands, Spain, 08025Consorcio Hospitalario Provincial de Castellon | Castellon Castellon, Spain, Hospital Puerta de Hierro Majadahonda | Majadahonda Madrid, Spain, 28220Complejo Hospitalario de Navarra | Pamplona Navarre, Spain, 31008Hospital Santa Creu i Sant Pau | Barcelona , Spain, 08025Inst Catala D'Oncologia | Barcelona , Spain, Hospital Universitario La Paz | Madrid , Spain, 28046Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro | Madrid , Spain, Hospital San Carlos Madrid | Madrid , Spain, Hospital Universitario Miguel Servet | Zaragoza , Spain,
Study Documents (Full Text)
Documents provided by ImmunityBio, Inc.: Study Protocol and Statistical Analysis Plan  January 20, 2016