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Soft Tissue SarcomaPhase 1/2NCT00742963

Dose-Escalation Study of TH-302 in Combination With Doxorubicin to Treat Patients With Advanced Soft Tissue Sarcoma

A Phase 1/2 study testing TH-302 in people with Soft Tissue Sarcoma, run by ImmunoGenesis at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether TH-302 in combination with Doxorubicin is safe and effective in the treatment of Advanced Soft Tissue Sarcoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
TH-302
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
107 participants
Where
9 sitesUnited States
Study dates
Aug 2008to Oct 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All Subjects:
  • At least 18 years of age
  • Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
  • Pathologically confirmed diagnosis of soft tissue sarcoma of the following subtypes:
  • Synovial sarcoma
  • High grade fibrosarcoma
Show all 30Show fewer
  • Unclassified, undifferentiated sarcoma
  • Liposarcoma
  • Leiomyosarcoma (excluding GIST)
  • Angiosarcoma (excluding Kaposi's sarcoma)
  • Pleomorphic sarcoma/malignant fibrous histiocytoma
  • Locally advanced unresectable or metastatic disease with no standard curative therapy available and for whom treatment with single agent doxorubicin is considered appropriate; subjects in the dose escalation cohorts must have progressed since their most recent systemic therapy
  • Recovered from reversible toxicities of prior therapy
  • Evaluable disease by RECIST criteria (at least one target or non-target lesion for dose escalation cohorts; at least 1 target lesion for dose expansion cohort)
  • ECOG performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Acceptable liver function:
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 times ULN
  • Acceptable renal function:
  • Serum creatinine within normal limits
  • Acceptable hematologic status (without hematologic support):
  • ANC ≥ 1500 cells/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 9.0 g/dL
  • Acceptable cardiac function:
  • Normal 12-lead ECG (clinically insignificant abnormalities permitted)
  • LVEF normal by MUGA or echocardiogram
  • Urinalysis: No clinically significant abnormalities
  • 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 or 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

Who cannot join

  • Prior therapy:
  • Dose escalation cohort: Prior treatment with more than 2 myelosuppressive cytotoxic chemotherapy regimens
  • Expanded cohort: Prior systemic therapy for advanced disease (neoadjuvant and adjuvant permitted)
  • Low grade tumors according to standard grading systems (eg AJCC Grade 1 and 2)
  • Prior therapy with ifosfamide or cyclophosphamide
  • Prior therapy with an anthracycline or anthracenedione
Show all 28Show fewer
  • Prior mediastinal/cardiac radiotherapy
  • Current use of drugs with known cardiotoxicity or known interactions with doxorubicin (see product label)
  • Anticancer treatment with radiation therapy, chemotherapy, targeted therapies (erlotinib, lapatinib, etc.), immunotherapy, hormones or other antitumor therapies within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
  • Significant cardiac dysfunction:
  • Any history of congestive heart failure
  • Any history of transmural myocardial infarction
  • 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 within the last 6 months
  • Seizure disorders requiring anticonvulsant therapy
  • Known brain metastases (unless previously treated and well controlled for a period of ≥ 3 months) Previously treated 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
  • 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 an hypoxic cytotoxin
  • Subjects who participated in an investigational drug or device study within 28 days prior to study entry
  • Known infection with HIV, hepatitis B, or hepatitis C
  • Subjects who have exhibited allergic reactions to a structural compound, biological agent, or formulation (containing solutol and/or propylene glycol) similar to TH-302
  • 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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Mary Crowley Cancer Research Centers

    Dallas, Texas, 75201

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46204

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

  • Washingon University Siteman Cancer Center

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Arizona Cancer Center

    Tucson, Arizona, 85719

Other trials in United States

About this study

Official title: A Phase 1/2, Multicenter, Dose-Escalation Study to Determine the Safety, Efficacy and Pharmacokinetics of TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma

The purpose of this study is to determine whether TH-302 in combination with Doxorubicin is safe and effective in the treatment of Advanced Soft Tissue Sarcoma.

Read the detailed description

A broad range of tumors have been shown to contain significant numbers of hypoxic cells and hypoxia has been shown to be associated with a poor prognosis and an increase in resistance to chemotherapy and radiotherapy (Brizel 1997, Vaupel 2007, Shannon 2003).

It is likely that an agent that could effectively target hypoxic regions in tumors would improve efficacy when combined with standard chemotherapy or radiotherapy. TH-302 is activated at lower oxygen concentrations than other bioreductive prodrugs (Duan 2008) and tirapazamine, a hypoxic cytotoxin that has been extensively studied in both preclinical and clinical studies. This should result in an improved therapeutic ratio (tumor vs normal tissue toxicity) as compared with other bioreductive agents. Because TH-302 is expected to be minimally toxic to aerobic cancer cells, optimal efficacy would be expected when TH-302 is combined with treatments that are most effective under aerobic conditions such as radiotherapy and cytotoxic chemotherapy. Preclinical data have shown at least additive efficacy when TH-302 is combined with chemotherapy. In order to minimize the risk of additive toxicity, TH-302 is not being evaluated in combination with alkylating agents. The study will enroll subjects with advanced soft tissue sarcoma. These tumors have evidence supporting the presence of hypoxia based on pO2 histography, F-MISO and gene expression profiling (Vaupel 2007, Francis 2007, Rajendran 2003).

Being tested
TH-302
Keywords
TH-302, Advanced Soft Tissue Sarcoma, Doxorubicin, Phase 1/2
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TH-302Drug

    TH-302 will be administered by IV infusion over 30-60 minutes on Days 1 and 8 of a 21-day cycle.

    Dose escalation dose levels:

    Dose level -1 (if needed): 180 mg/m2 Starting dose: 240 mg/m2

Study groups in NCT00742963
Study groupRoleWhat they receive
1Experimental75 mg/m2 of Doxorubicin administered by bolus injection starting on Day 1 of a 21-day cycle.
Receives: Drug: TH-302

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) Measured of TH-302 When Used in Combination With Doxorubicin and Prophylactic Growth Factor Support in Subjects With Advanced Soft Tissue Sarcoma

    Measured: Two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionJul 2013
  4. Study completionOct 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00742963
Sponsor's protocol ID
TH-CR-403
Status last verified
May 2025
First submitted
26 Aug 2008
Last updated
13 May 2025
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TH-302 in people with Soft Tissue Sarcoma, run by ImmunoGenesis at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) Measured of TH-302 When Used in Combination With Doxorubicin and Prophylactic Growth Factor Support in Subjects With Advanced Soft Tissue Sarcoma (time frame: Two years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00742963.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.

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