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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02049905




Registration number
NCT02049905
Ethics application status
Date submitted
28/01/2014
Date registered
30/01/2014
Date last updated
7/06/2017

Titles & IDs
Public title
Phase 3 Study to Treat Patients With Soft Tissue Sarcomas
Scientific 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
Secondary ID [1] 0 0
ALDOXORUBICIN-P3-STS-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic, Locally Advanced or Unresectable Soft Tissue Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aldoxorubicin
Treatment: Drugs - Investigator's Choice Treatment (Darcabazine, Pazopanib, Gemcitabine + Docetaxel, Doxorubicin, Ifosfamide)

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.

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.


Treatment: Drugs: Aldoxorubicin


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


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) - 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.
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Overall Survival (OS) - 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.
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Safety Measures - 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.
Timepoint [2] 0 0
24 months

Eligibility
Key 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.
Minimum age
15 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Saint Leonards
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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California
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United States of America
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Colorado
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Florida
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United States of America
State/province [6] 0 0
Georgia
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United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Tennessee
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Vermont
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United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Chile
State/province [25] 0 0
Temuco Cautin
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Denmark
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Herlev
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France
State/province [27] 0 0
Aquitaine
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France
State/province [28] 0 0
Bourgogne
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France
State/province [29] 0 0
Ile-de-France
Country [30] 0 0
France
State/province [30] 0 0
Rhone-Alpes
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France
State/province [31] 0 0
Centre
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Hungary
State/province [32] 0 0
Budapest
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Israel
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Jerusalem
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Israel
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Haifa
Country [35] 0 0
Israel
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Tel Aviv
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Israel
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Tel-Heshomer
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Italy
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Torino
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Italy
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Bologna
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Italy
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Milano
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Italy
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Padova
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Netherlands
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Zuid-Holland
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Poland
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Warszawa
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Russian Federation
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Moscow
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Russian Federation
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Tatarstan
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Spain
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Baleares
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Spain
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Madrid
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Spain
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Navarra
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Spain
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Barcelona
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Spain
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Castellon
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Spain
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Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
CytRx
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02049905
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications