Phase 3 Study to Treat Patients With Soft Tissue Sarcomas

NCT02049905 | Completed Phase 3 Results DMC

• 1 other identifier: ALDOXORUBICIN-P3-STS-01
• Study Type: interventional
• Target: 433
• Locations: 13 countries
• Sites: 74

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

Keywords

soft tissue sarcoma; unresectable; metastatic; locally advanced; sarcoma

Outcome Measures

Primary Outcomes (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.

  24 months

Study Arms (2)

Aldoxorubicin

EXPERIMENTAL

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

ACTIVE COMPARATOR

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)

Interventions

Aldoxorubicin DRUG

Also known as: INNO-206

Aldoxorubicin

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

Also known as: Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide

Investigator's Choice of Treatment

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (74)

University of Alabama at Birmingham

Birmingham, Alabama, 35243, United States

Location

Arizona Oncology Associates, PC

Phoenix, Arizona, 85016, United States

Location

The University of Arizona

Tucson, Arizona, 85719, United States

Location

City of Hope Medical Group

Duarte, California, 91010, United States

Location

Samuel Oschin Cancer Center

Los Angeles, California, 90048, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 940403, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

U of CO Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Georgia Cancer Specialists

Atlanta, Georgia, 30341, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Edward Cancer Center

Naperville, Illinois, 60540, United States

Location

Oncology Specialists, SC

Niles, Illinois, 60714, United States

Location

Kansas City Cancer Center

Overland Park, Kansas, 66210, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43202, United States

Location

Center for Health and Healing

Portland, Oregon, 97239, United States

Location

Jefferson Medical College

Philadelphia, Pennsylvania, 19107, United States

Location

U of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Fletcher Allen Health Care

Burlington, Vermont, 05405, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Location

Westmead Hospital

Westmead, New South Wales, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

Juravinski Cancer Center

Hamilton, Ontario, LBV5C2, Canada

Location

McGill University

Montreal, Quebec, H2W156, Canada

Location

Instituto Clinico Oncologica del Sur (ICOS)

Temuco, Región de la Araucanía, Chile

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Institut Bergonie

Bordeaux, Aquitaine, France

Location

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Location

Centre Georges Francois Leclerc

Dijon, Bourgogne-Franche-Comté, France

Location

Centre Hospitalier Regional et Universitaire - Hospital Bretonneau

Tours, Centre-Val de Loire, France

Location

Hopital Rene Huguenin - Institut Curie

Saint-Cloud, Île-de-France Region, France

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94800, France

Location

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, Hungary

Location

Rambam Medical Center

Haifa, Israel

Location

Sharet Institute of Oncology Hadassah Ein Karem Medical Center

Jerusalem, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna-Policlinico S Orsola-Malpighi

Bologna, Italy

Location

IRCCS Instituto Ortopedico Rizzoli

Bologna, Italy

Location

Istituto Europeo di Oncologia Milano

Milan, 20141, Italy

Location

Istituto Oncologico Veneto

Padua, 35128, Italy

Location

Leiden Universitair Medisch Centrum

Leiden, South Holland, 2333ZA, Netherlands

Location

Instytut im.Marii Sklodowskiej-Curie

Warsaw, Poland

Location

State Institution "Blokhin Cancer Research Centre RAMS"

Moscow, 115478, Russia

Location

City Oncology Hospital #2

Moscow, 143423, Russia

Location

Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan

Tatarstan, 420029, Russia

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 08025, Spain

Location

Consorcio Hospitalario Provincial de Castellon

Castellon, Castellon, Spain

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28220, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Inst Catala D'Oncologia

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

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

Madrid, Spain

Location

Hospital San Carlos Madrid

Madrid, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

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MeSH Terms

Conditions

Neoplasm Metastasis; Sarcoma

Interventions

DOXO-EMCH; pazopanib; Gemcitabine; Docetaxel; Doxorubicin; Ifosfamide

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@Immunitybio.com

855-797-9277

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: January 30, 2014
• Study Start: January 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: June 13, 2024
• Results First Posted: June 13, 2024

Record last verified: 2017-06

Locations

CL (1); RU (3); DK (1); ES (10); HU (1); US (36); CA (3); NL (1); AU (2); FR (6); IT (5); IL (4); PL (1)