Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma Clinical Trial
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
| Verified date | June 2017 |
| Source | ImmunityBio, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 433 |
| Est. completion date | May 2017 |
| Est. primary completion date | May 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 15 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Royal North Shore Hospital | Saint Leonards | New South Wales |
| Australia | Westmead Hospital | Westmead | New South Wales |
| Canada | Cross Cancer Institute | Edmonton | Alberta |
| Canada | Juravinski Cancer Center | Hamilton | Ontario |
| Canada | McGill University | Montreal | Quebec |
| Chile | Instituto Clinico Oncologica del Sur (ICOS) | Temuco | Araucanía |
| Denmark | Herlev Hospital | Herlev | |
| France | Institut Bergonie | Bordeaux Cedex | Aquitaine |
| France | Centre Georges Francois Leclerc | Dijon | Bourgogne |
| France | Centre Leon Berard | Lyon | Rhone-Alpes |
| France | Hopital Rene Huguenin - Institut Curie | Saint-Cloud | Ile-de-France |
| France | Centre Hospitalier Regional et Universitaire - Hospital Bretonneau | Tours | Centre-Val-de-Loire |
| France | Institut Gustave Roussy | Villejuif | Ile-de-France |
| Hungary | Magyar Honvedseg Egeszsegugyi Kozpont | Budapest | |
| Israel | 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 | |
| Italy | Azienda Ospedaliero-Universitaria di Bologna-Policlinico S Orsola-Malpighi | Bologna | |
| Italy | IRCCS Instituto Ortopedico Rizzoli | Bologna | |
| Italy | Fondazione del Piemonte per l'Oncologia | Candiolo | Torino |
| Italy | Istituto Europeo di Oncologia Milano | Milano | |
| Italy | Istituto Oncologico Veneto | Padova | |
| Netherlands | Leiden Universitair Medisch Centrum | Leiden | Zuid-Holland |
| Poland | Instytut im.Marii Sklodowskiej-Curie | Warszawa | |
| Russian Federation | City Oncology Hospital #2 | Moscow | |
| Russian Federation | State Institution "Blokhin Cancer Research Centre RAMS" | Moscow | |
| Russian Federation | Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan | Tatarstan | |
| Spain | Hospital Santa Creu i Sant Pau | Barcelona | |
| Spain | Inst Catala D'Oncologia | Barcelona | |
| Spain | Consorcio Hospitalario Provincial de Castellon | Castellón de la Plana | Castellon |
| Spain | Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro | Madrid | |
| Spain | Hospital San Carlos Madrid | Madrid | |
| Spain | Hospital Universitario La Paz | Madrid | |
| Spain | Hospital Puerta de Hierro Majadahonda | Majadahonda | Madrid |
| Spain | Hospital Universitario Son Espases | Palma de Mallorca | Baleares |
| Spain | Complejo Hospitalario de Navarra | Pamplona | Navarra |
| Spain | Hospital Universitario Miguel Servet | Zaragoza | |
| United States | University of Michigan | Ann Arbor | Michigan |
| United States | Georgia Cancer Specialists | Atlanta | Georgia |
| United States | U of CO Health Sciences Center | Aurora | Colorado |
| United States | University of Alabama at Birmingham | Birmingham | Alabama |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| United States | Fletcher Allen Health Care | Burlington | Vermont |
| United States | Levine Cancer Institute | Charlotte | North Carolina |
| United States | Northwestern Medical Faculty Foundation | Chicago | Illinois |
| United States | Cleveland Clinic | Cleveland | Ohio |
| United States | University Hospitals Case Medical Center | Cleveland | Ohio |
| United States | The James Cancer Hospital and Solove Research Institute | Columbus | Ohio |
| United States | Rocky Mountain Cancer Centers | Denver | Colorado |
| United States | City of Hope Medical Group | Duarte | California |
| United States | Mayo Clinic | Jacksonville | Florida |
| United States | Samuel Oschin Cancer Center | Los Angeles | California |
| United States | UCLA Medical Center | Los Angeles | California |
| United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
| United States | University of Minnesota | Minneapolis | Minnesota |
| United States | Edward Cancer Center | Naperville | Illinois |
| United States | Vanderbilt University | Nashville | Tennessee |
| United States | Oncology Specialists, SC | Niles | Illinois |
| United States | Nebraska Methodist Hospital | Omaha | Nebraska |
| United States | Kansas City Cancer Center | Overland Park | Kansas |
| United States | Jefferson Medical College | Philadelphia | Pennsylvania |
| United States | Arizona Oncology Associates, PC | Phoenix | Arizona |
| United States | U of Pittsburgh Cancer Institute | Pittsburgh | Pennsylvania |
| United States | Center for Health and Healing | Portland | Oregon |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | Washington University | Saint Louis | Missouri |
| United States | Sarcoma Oncology Center | Santa Monica | California |
| United States | Stanford University Medical Center | Stanford | California |
| United States | Moffitt Cancer Center | Tampa | Florida |
| United States | The University of Arizona | Tucson | Arizona |
| United States | Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| ImmunityBio, Inc. |
United States, Australia, Canada, Chile, Denmark, France, Hungary, Israel, Italy, Netherlands, Poland, Russian Federation, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. |
24 months |