Phase 3 Study to Treat Patients With Soft Tissue Sarcomas

Sponsor

ImmunityBio, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02049905

Collaborator

(none)

433

Enrollment

Locations

Arms

Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma	Drug: Aldoxorubicin Drug: Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

433 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2014

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 Other Names: INNO-206
Active Comparator: Investigator's Choice of Treatment These treatments include: 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; Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 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; 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 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) Other Names: Darcabazine Pazopanib Gemcitabine + Docetaxel Doxorubicin Ifosfamide

Arm

Intervention/Treatment

Experimental: 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

Other Names:

INNO-206

Active Comparator: Investigator's Choice of Treatment

These treatments include: 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; Pazopanib, 800 mg orally each day until tumor progression or unacceptable toxicity occurs; 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; 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 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)

Other Names:

Darcabazine

Pazopanib

Gemcitabine + Docetaxel

Doxorubicin

Ifosfamide

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) [24 months]
PFS is defined as the time from the date of randomization to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.

Secondary Outcome Measures

Overall Survival (OS) [36 months]
Overall survival is defined as the time from randomization to date of death. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.
Safety Measures [24 months]
The safety of aldoxorubicin compared to investigator's choice in this population assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiogram (ECHO) evaluations, electrocardiogram (ECG) results, and weight, as well as disease control rate and tumor response.

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35243
2	Arizona Oncology Associates, PC	Phoenix	Arizona	United States	85016
3	The University of Arizona	Tucson	Arizona	United States	85719
4	City of Hope Medical Group	Duarte	California	United States	91010
5	Samuel Oschin Cancer Center	Los Angeles	California	United States	90048
6	UCLA Medical Center	Los Angeles	California	United States	90095
7	Sarcoma Oncology Center	Santa Monica	California	United States	940403
8	Stanford University Medical Center	Stanford	California	United States	94305
9	U of CO Health Sciences Center	Aurora	Colorado	United States	80045
10	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
11	Mayo Clinic	Jacksonville	Florida	United States	32224
12	Moffitt Cancer Center	Tampa	Florida	United States	33612
13	Georgia Cancer Specialists	Atlanta	Georgia	United States	30341
14	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
15	Edward Cancer Center	Naperville	Illinois	United States	60540
16	Oncology Specialists, SC	Niles	Illinois	United States	60714
17	Kansas City Cancer Center	Overland Park	Kansas	United States	66210
18	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
19	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
20	University of Michigan	Ann Arbor	Michigan	United States	48109
21	University of Minnesota	Minneapolis	Minnesota	United States	55455
22	Mayo Clinic	Rochester	Minnesota	United States	55905
23	Washington University	Saint Louis	Missouri	United States	63110
24	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
25	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
26	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
27	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
28	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
29	Cleveland Clinic	Cleveland	Ohio	United States	44195
30	The James Cancer Hospital and Solove Research Institute	Columbus	Ohio	United States	43202
31	Center for Health and Healing	Portland	Oregon	United States	97239
32	Jefferson Medical College	Philadelphia	Pennsylvania	United States	19107
33	U of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
34	Vanderbilt University	Nashville	Tennessee	United States	37212
35	Fletcher Allen Health Care	Burlington	Vermont	United States	05405
36	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
37	Royal North Shore Hospital	Saint Leonards	New South Wales	Australia
38	Westmead Hospital	Westmead	New South Wales	Australia
39	Cross Cancer Institute	Edmonton	Alberta	Canada
40	Juravinski Cancer Center	Hamilton	Ontario	Canada	LBV5C2
41	McGill University	Montreal	Quebec	Canada	H2W156
42	Instituto Clinico Oncologica del Sur (ICOS)	Temuco	Araucanía	Chile
43	Herlev Hospital	Herlev		Denmark	2730
44	Institut Bergonie	Bordeaux Cedex	Aquitaine	France
45	Centre Georges Francois Leclerc	Dijon	Bourgogne	France
46	Centre Hospitalier Regional et Universitaire - Hospital Bretonneau	Tours	Centre-Val-de-Loire	France
47	Hopital Rene Huguenin - Institut Curie	Saint-Cloud	Ile-de-France	France
48	Institut Gustave Roussy	Villejuif	Ile-de-France	France	94800
49	Centre Leon Berard	Lyon	Rhone-Alpes	France
50	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest		Hungary
51	Rambam Medical Center	Haifa		Israel
52	Sharet Institute of Oncology Hadassah Ein Karem Medical Center	Jerusalem		Israel
53	Chaim Sheba Medical Center	Ramat Gan		Israel
54	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel
55	Fondazione del Piemonte per l'Oncologia	Candiolo	Torino	Italy
56	Azienda Ospedaliero-Universitaria di Bologna-Policlinico S Orsola-Malpighi	Bologna		Italy
57	IRCCS Instituto Ortopedico Rizzoli	Bologna		Italy
58	Istituto Europeo di Oncologia Milano	Milano		Italy	20141
59	Istituto Oncologico Veneto	Padova		Italy	35128
60	Leiden Universitair Medisch Centrum	Leiden	Zuid-Holland	Netherlands	2333ZA
61	Instytut im.Marii Sklodowskiej-Curie	Warszawa		Poland
62	State Institution "Blokhin Cancer Research Centre RAMS"	Moscow		Russian Federation	115478
63	City Oncology Hospital #2	Moscow		Russian Federation	143423
64	Republican Clinical Oncologic Dispensary of Ministry of Health Republic Tatarstan	Tatarstan		Russian Federation	420029
65	Hospital Universitario Son Espases	Palma de Mallorca	Baleares	Spain	08025
66	Consorcio Hospitalario Provincial de Castellon	Castellón de la Plana	Castellon	Spain
67	Hospital Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28220
68	Complejo Hospitalario de Navarra	Pamplona	Navarra	Spain	31008
69	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08025
70	Inst Catala D'Oncologia	Barcelona		Spain
71	Hospital Universitario La Paz	Madrid		Spain	28046
72	Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro	Madrid		Spain
73	Hospital San Carlos Madrid	Madrid		Spain
74	Hospital Universitario Miguel Servet	Zaragoza		Spain