EUCTR2011-003145-17-DKActive, not recruitingPhase 1
A Randomized Phase 3, Multicenter, Open-Label Study Comparing TH-302 in Combination with Doxorubicin vs. Doxorubicin Alone in Subjects with Locally Advanced Unresectable or MetastaticSoft Tissue Sarcoma
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 620
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional clinical trial of medicinal product
Eligibility Criteria
- Sex
- All
Inclusion Criteria
- •1. Male or female = 15 years of age
- •2. Ability to understand the purposes and risks of the study and has signed or, if appropriate, the subject’s parent or legal guardian has signed a written informed consent form approved by the investigator’s IRB/Ethics Committee
- •3. Pathologically confirmed diagnosis of soft tissue sarcoma of the following histopathologic types:
- •? Other soft tissue sarcomas for which doxorubicin is appropriate first line therapy
- •? Synovial sarcoma
- •? High grade fibrosarcoma
- •? Undifferentiated sarcoma; sarcoma not otherwise specified (NOS)
- •? Liposarcoma
- •? Leiomyosarcoma (excluding GIST)
- •? Angiosarcoma (excluding Kaposi’s sarcoma)
- •? Malignant peripheral nerve sheath tumor
- •? Pleomorphic Rhabdomyosarcoma
- •? Myxofibrosarcoma
- •? Epithelioid sarcoma
- •? Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (MFH) (including pleomorphic, giant cell, myxoid and inflammatory forms)
- •4. Locally advanced unresectable or metastatic disease with no standard curative therapy available and for whom treatment with single agent doxorubicin is considered appropriate
- •5. Recovered from reversible toxicities of prior therapy
- •6. Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields or progressed within a previous radiation field)
- •7. ECOG performance status of 0 or 1
- •8. Life expectancy of at least 3 months
- •9. Acceptable liver function:
- •? Bilirubin = 1.5 x upper limit of normal (ULN); does not apply to subjects with Gilbert’s syndrome
- •? AST (SGOT) and ALT (SGPT) = 3.0 x ULN); if liver metastases are present, then = 5 x ULN is allowed
- •10. Acceptable renal function:
- •? Serum creatinine = 1.5 times ULN or calculated creatinine clearance = 60 mL/min (by the Cockcroft Gault formula)
- •11. Acceptable hematologic status (without growth factor
- •support or transfusion dependency):
- •? ANC = 1500 cells/µL
- •? Platelet count = 100,000/µL
- •? Hemoglobin = 9.0 g/dL
- •12. Acceptable cardiac function:
- •? Normal 12-lead ECG (clinically insignificant abnormalities permitted)
- •? LVEF normal by MUGA or echocardiogram (>50% per CTCAE v4.0)
- •13. All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into
- •the study through 6 months after the last dose. Post-menopausal women must meet the criteria of 12 months of natural(spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >35 mIU/ml (IU/L).
- •Are the trial subjects under 18? yes
- •Number of subjects for this age range: 10
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 410
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 200
Exclusion Criteria
- •1. Low grade tumors according to standard grading systems (eg AJCC Grade 1 and 2 or FNCLCC Grade 1)
- •2. Prior systemic therapy for advanced or metastatic soft tissue sarcoma (neoadjuvant therapy followed by surgical resection and adjuvant therapy permitted). Palliative radiotherapy to non-target lesions is allowed if completed at least two weeks prior to study entry.
- •3. Prior soft tissue sarcoma therapy with ifosfamide or cyclophosphamide or other nitrogen mustards
- •4. Prior systemic therapy with an anthracycline or anthracenedione
- •5. Prior mediastinal/cardiac radiotherapy
- •6. Current use of drugs with known cardiotoxicity or known interactions with doxorubicin
- •7. Anti-cancer treatment with radiation therapy, neoadjuvant or adjuvant chemotherapy, targeted therapies, immunotherapy, hormones or other antitumor therapies within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
- •8. Significant cardiac dysfunction precluding treatment with doxorubicin:
- •? History of congestive heart failure
- •? Myocardial infarction within the past 6 months or severe myocardial insufficiency
- •? Uncontrolled arrhythmias within the past 6 months
- •? Angina pectoris requiring antianginal medication within the past 6 months
- •? Clinically significant valvular heart disease
- •? Poorly controlled hypertension
- •9. Seizure disorders requiring anticonvulsant therapy unless seizure-free for the last year
- •10. Known brain metastases (unless previously treated and well controlled for a period of = 3 months)
- •11. Previously diagnosed malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
- •12. Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
- •13. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
- •14. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- •15. Prior therapy with a hypoxic cytotoxin
- •16. Subjects who participated in an investigational drug or device study within 28 days prior to study entry
- •17. Known infection with HIV, or active infection with hepatitis B, or hepatitis C
- •18. Subjects who have exhibited allergic reactions to a structural compoundsimilar to TH-302 or the drug product excipients
- •19. Females who are pregnant or breast-feeding
- •20. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
- •21. Unwillingness or inability to comply with the study protocol for any reason
Investigators
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