Phase 3 Study to Treat Patients With Soft Tissue Sarcomas

NCT ID: NCT02049905

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 433 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2017-05-31

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.

Conditions

Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Aldoxorubicin

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)

Intervention Type: DRUG

Interventions

Aldoxorubicin

Intervention Type: DRUG

Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)

Intervention Type: DRUG

Other Intervention Names

INNO-206; Darcabazine; Pazopanib; Gemcitabine + Docetaxel; Doxorubicin; Ifosfamide

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.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ImmunityBio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Arizona Oncology Associates, PC

Phoenix, Arizona, United States

The University of Arizona

Tucson, Arizona, United States

City of Hope Medical Group

Duarte, California, United States

Samuel Oschin Cancer Center

Los Angeles, California, United States

UCLA Medical Center

Los Angeles, California, United States

Sarcoma Oncology Center

Santa Monica, California, United States

Stanford University Medical Center

Stanford, California, United States

U of CO Health Sciences Center

Aurora, Colorado, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Mayo Clinic

Jacksonville, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Georgia Cancer Specialists

Atlanta, Georgia, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Edward Cancer Center

Naperville, Illinois, United States

Oncology Specialists, SC

Niles, Illinois, United States

Kansas City Cancer Center

Overland Park, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Center for Health and Healing

Portland, Oregon, United States

Jefferson Medical College

Philadelphia, Pennsylvania, United States

U of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

Fletcher Allen Health Care

Burlington, Vermont, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Royal 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

McGill University

Montreal, Quebec, Canada

Instituto Clinico Oncologica del Sur (ICOS)

Temuco, Región de la Araucanía, Chile

Herlev Hospital

Herlev, , Denmark

Institut 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

Magyar 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

Istituto Oncologico Veneto

Padua, , Italy

Leiden Universitair Medisch Centrum

Leiden, South Holland, Netherlands

Instytut im.Marii Sklodowskiej-Curie

Warsaw, , Poland

State Institution "Blokhin Cancer Research Centre RAMS"

Moscow, , Russia

City Oncology Hospital #2

Moscow, , Russia

Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan

Tatarstan, , Russia

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Consorcio Hospitalario Provincial de Castellon

Castellon, Castellon, Spain

Hospital Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Inst Catala D'Oncologia

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro

Madrid, , Spain

Hospital San Carlos Madrid

Madrid, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

United States; Australia; Canada; Chile; Denmark; France; Hungary; Israel; Italy; Netherlands; Poland; Russia; Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://doi.org/10.1093/annonc/mdu354.50

Related Info

https://pubmed.ncbi.nlm.nih.gov/30936721/

Related Info

https://pubmed.ncbi.nlm.nih.gov/30873850/

Related Info

https://pubmed.ncbi.nlm.nih.gov/29869517/

Related Info

https://pubmed.ncbi.nlm.nih.gov/28846045/

Related Info

https://pubmed.ncbi.nlm.nih.gov/?term=rubicin%3A+a+tumor-targeted+doxorubicin+conjugate+for+relapsed+or+refractory+soft+tissue+sarcomas

Related Info

Other Identifiers

ALDOXORUBICIN-P3-STS-01

Identifier Type: -

Identifier Source: org_study_id