A Japanese Trial of TH-302 in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma
Condition: Soft Tissue Sarcoma
MeSH terms: Sarcoma
Intervention: TH-302; Doxorubicin
Intervention description: TH-302 will be administered at a dose of 300 milligram per square meter (mg/m^2) by intravenous infusion over 30 minutes on Days 1 and 8 of every 21-day cycle until the evidence of significant treatment-related toxicity or progressive disease.; Doxorubicin will be administered at a dose of 75 mg/m^2 by intravenous injection (over at least 5 minutes) or by intravenous infusion over 6-96 hours on Day 1 of every 21-day cycle starting 2 to 4 hours after completion of TH-302 administration until the evidence of significant treatment-related toxicity or progressive disease.
Intervention MeSH terms: Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma; TH-302; Doxorubicin; Evofosfamide

Summary:

      This is a Phase 2, single-arm, Japanese multicenter trial to evaluate the safety,
      tolerability, and efficacy of TH-302 in combination with doxorubicin in subjects with locally
      advanced unresectable or metastatic soft tissue sarcoma (STS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female Japanese subjects greater than or equal to (>=) 15 years of age

          -  Able to understand the purposes and risks of the trial and has signed or, if
             appropriate, the subject's parent or legal guardian has signed a written informed
             consent form approved by the Institutional Review Board (IRB) or Independent Ethics
             Committee (IEC)

          -  Pathologically confirmed diagnosis of STS of the histopathologic types as specified in
             the protocol

          -  Locally advanced unresectable or metastatic disease with no standard curative therapy
             available and for whom treatment with single agent doxorubicin is considered
             appropriate

          -  Recovered from reversible toxicities of prior therapy

          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) Version
             1.1 (at least one target lesion outside of previous radiation fields or progressed
             within a previous radiation field)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy of at least 3 months

          -  Acceptable liver function, renal function, hematologic status (without growth factor
             support for neutropenia or transfusion dependency), and cardiac function as specified
             in the protocol

          -  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 intrauterine device, intrauterine device [IUD]) with their
             partner from entry into the trial 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 follicle-stimulating
             hormone (FSH) levels greater than (>) 35 international units per liter (IU/L)

        Exclusion Criteria:

          -  Low grade tumors according to standard grading systems (for example, American Joint
             Committee on Cancer [AJCC] Grade 1 and 2 or Fédération Nationale des Centres de Lutte
             Contre le Cancer [FNCLCC] Grade 1)

          -  Prior systemic therapy for advanced or metastatic STS (neoadjuvant therapy followed by
             surgical resection and adjuvant therapy permitted)

          -  Prior STS therapy with ifosfamide or cyclophosphamide or other nitrogen mustards;
             prior systemic therapy with an anthracycline or anthracenedione; or prior
             mediastinal/cardiac radiotherapy

          -  Current use of drugs with known cardiotoxicity or known interactions with doxorubicin

          -  Anti-cancer treatment with radiation therapy, neoadjuvant or adjuvant chemotherapy,
             targeted therapies, immunotherapy, hormones or other antitumor therapies within 4
             weeks prior to trial entry (6 weeks for nitrosoureas or mitomycin C).

          -  Significant cardiac dysfunction precluding treatment with doxorubicin as specified in
             the protocol

          -  Seizure disorders requiring anticonvulsant therapy unless seizure-free for the last
             year

          -  Known brain metastases (unless previously treated and well controlled for a period of
             >=3 months before screening)

          -  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 before screening

          -  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

          -  Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without
             complete recovery

          -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

          -  Prior therapy with a hypoxic cytotoxin

          -  Subjects who participated in an investigational drug or device trial within 28 days
             prior to trial entry

          -  Known infection with human immunodeficiency virus (HIV) or active infection with
             hepatitis B or hepatitis C

          -  Subjects who have exhibited allergic reactions to a structural compound similar to
             TH-302 or the drug product excipients

          -  Subjects who are taking medications that prolong QT interval and have a risk of
             Torsades de Pointes

          -  Subjects with a corrected QT (QTc) interval calculated according to Bazett's formula
             of >450 milliseconds (msec) based on a screening electrocardiogram (ECG)

          -  Subjects with a history of long QT syndrome

          -  Subjects taking a medication that is a moderate or strong inhibitor or inducer of
             cytochrome P450 3A4 (CYP3A4)

          -  Females who are pregnant or breast-feeding

          -  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

          -  Unwillingness or inability to comply with the study protocol for any reason

          -  Legal incapacity or limited legal capacity