Metastatic MelanomaPhase 2NCT01864538
A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
A Phase 2 study testing TH-302 in people with Metastatic Melanoma, run by ImmunoGenesis at 7 sites in 2 countries.
Trial summary
The primary objective of this study is to determine the response rate, duration of response,progression-free survival and overall survival of subjects with advanced melanoma treated with TH-302. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- 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
- 11 participants
- Where
- 7 sitesin 2 countries
- Study dates
- May 2013to Sep 2015
- Phase
- Phase 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
- 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 Regional Ethics Board/Independent Ethics Committee (REB/IEC)
- Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent or metastatic and is not curable by surgical or other means.
- Adequate tumour tissue (greater than 0.5cm3 preferred, 3 X core biopsy acceptable) available and agreement from subjects that this tissue from their primary and/or metastatic tumour be made available for assessment of potential biomarkers.
- Ability and availability to complete all prescribed biomarker studies (Screening and after Cycle 2).
- Recovered to Grade 1 from reversible toxicities of prior therapy
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- Presence of clinically and/or radiologically documented disease. At least one site of disease (which will not be removed during the course of the study) must be uni-dimensionally measurable as per RECIST 1.1 or clinically quantifiable (such as in the case of skin disease)
- ECOG performance status of 0 - 1.
- Prior treatment with any number of immunotherapies (e.g., IL2, ipilimumab), targeted therapies (e.g., vemurafenib) are permitted but no more than one 1 prior chemotherapy
- Acceptable liver function
- Acceptable renal function
- Acceptable hematologic status (without growth factor support for neutropenia or transfusion dependency):
- Normal 12-lead ECG (clinically insignificant abnormalities permitted)
- Female subjects of childbearing age must have a negative urine HCG test unless prior hysterectomy or menopause (defined as age above 55 and twelve months without menstrual activity). Female subjects should not become pregnant or breast-feed while on this study. Sexually active male and female subjects should use effective birth control.
Who cannot join
- Anticancer treatment with radiation therapy, targeted therapies, chemotherapy, immunotherapy, hormones or other antitumour therapies within 28 days prior to first dose of TH-302.
- Subjects who have received any other investigational drug or agent within 28 days of first dose of TH-302
- Current use of drugs with known cardiotoxicity
- Significant cardiac dysfunction:
- Seizure disorders requiring anticonvulsant therapy
- Progressing brain metastases (unless previously treated and stable disease for a period of greater than or equal to 3 months on repeat MRI following definitive treatment).
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- History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for greater than 2 years
- Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation less than 90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause hypoxia of normal tissue.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Prior therapy with an hypoxic cytotoxin
- Known infection with HIV or active infection with hepatitis B or hepatitis C
- History of allergic reaction to a structural compound or biological agent similar to TH-302
- Pregnancy 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
7 sites in 2 countries.
7 sites in 2 countries
Canada4 sites
Cross Cancer Institute
Edmonton, Alberta, T6G1Z2
Juravinski Cancer Centre
Hamilton, Ontario, L8V5C2
London Health Sciences Centre
London, Ontario, N6A4L6
Princess Margaret Hospital
Toronto, Ontario, M5G2M9
United States3 sites
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
UCLA
Los Angeles, California, 90404
Columbia University Medical Center
New York, New York, 10032
About this study
The primary objective of this study is to determine the response rate, duration of response,progression-free survival and overall survival of subjects with advanced melanoma treated with TH-302.
Read the detailed description
Hypoxia is an independent marker of a poor prognosis for subjects with metastatic melanoma (Simonetti 2012, Lartigau 1997). Hypoxic melanoma cells are more likely to exhibit a stem-cell like phenotype with an associated increased propensity for invasion, angiogenesis, and metastasis formation compared to normoxic cells. Moreover, this phenotype is also associated with treatment resistance. TH-302, a hypoxia activated prodrug (HAP), was designed to target the hypoxic nature of tumours while having a minimal effect on normoxic tissue. TH-302 belongs to a class of alkylating agents that have significant experimental and clinical activity (Brock 1989). Preclinical data support the hypothesis that TH-302 targets hypoxic regions of tumours and is also able to kill tumour cells in normoxic regions as a result of cytotoxin diffusion, leading to significant effects on tumour growth (Meng 2011). TH-302 has been investigated in over 700 subjects with solid tumours or hematologic malignancies, including subjects with metastatic melanoma. In this subset a disease control rate of 63% (3 subjects with partial responses and 9 subjects with stable disease out of a total of 19) was observed in an early phase clinical trial of TH-302 (Weber 2010). Predictive biomarkers for response and toxicity have yet to be identified for subjects with advanced melanoma treated with TH-302. Optimal patient selection may be critical to maximize the clinical benefit. A predictive biomarker approach will be investigated to try to identify subjects most likely to benefit from TH-302. Given the hypoxia-targeting mechanism of TH- 302, it is believed that hypoxia biomarkers will be the most informative for identifying subjects likely to benefit from TH- 302; however, additional biomarkers including DNA repair biomarkers will also be investigated. In addition, this approach will also have potential to synergise with future immunotherapeutic approaches as suppressive T regulatory cells are thought to reside within hypoxic niches within the tumour microenvironment that would be amenable to targeting by TH-302.
- Conditions
- Metastatic Melanoma
- Being tested
- TH-302
- Keywords
- TH-302, Advanced Melanoma, Metastatic, Biomarker, Mucosal Melanoma, Evofosfamide
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-302Drug
480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| TH-302 | Experimental | 480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle. Receives: Drug: TH-302 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startMay 2013
- Primary completionSep 2015
- Study completionSep 2015
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- ImmunoGenesis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tillman Pearce, MD, Study director, Threshold Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864538
- Sponsor's protocol ID
- TH-CR-413
- Status last verified
- May 2025
- First submitted
- 13 May 2013
- Last updated
- 11 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT01864538
- Acronym / sponsor ID
- TH-CR-413
- Conditions
- Metastatic Melanoma
- Keywords
- TH-302, Advanced Melanoma, Metastatic, Biomarker, Mucosal Melanoma, Evofosfamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 11 participants (actual)
- Lead sponsor
- ImmunoGenesisIndustry (pharma, biotech, devices)
- Study start
- May 2013 (actual)
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 29 May 2013 (estimated)
- Results
- Posted 16 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine the response rate, duration of response,progression-free survival and overall survival of subjects with advanced melanoma treated with TH-302.
Detailed description
Hypoxia is an independent marker of a poor prognosis for subjects with metastatic melanoma (Simonetti 2012, Lartigau 1997). Hypoxic melanoma cells are more likely to exhibit a stem-cell like phenotype with an associated increased propensity for invasion, angiogenesis, and metastasis formation compared to normoxic cells. Moreover, this phenotype is also associated with treatment resistance. TH-302, a hypoxia activated prodrug (HAP), was designed to target the hypoxic nature of tumours while having a minimal effect on normoxic tissue. TH-302 belongs to a class of alkylating agents that have significant experimental and clinical activity (Brock 1989). Preclinical data support the hypothesis that TH-302 targets hypoxic regions of tumours and is also able to kill tumour cells in normoxic regions as a result of cytotoxin diffusion, leading to significant effects on tumour growth (Meng 2011). TH-302 has been investigated in over 700 subjects with solid tumours or hematologic malignancies, including subjects with metastatic melanoma. In this subset a disease control rate of 63% (3 subjects with partial responses and 9 subjects with stable disease out of a total of 19) was observed in an early phase clinical trial of TH-302 (Weber 2010). Predictive biomarkers for response and toxicity have yet to be identified for subjects with advanced melanoma treated with TH-302. Optimal patient selection may be critical to maximize the clinical benefit. A predictive biomarker approach will be investigated to try to identify subjects most likely to benefit from TH-302. Given the hypoxia-targeting mechanism of TH- 302, it is believed that hypoxia biomarkers will be the most informative for identifying subjects likely to benefit from TH- 302; however, additional biomarkers including DNA repair biomarkers will also be investigated. In addition, this approach will also have potential to synergise with future immunotherapeutic approaches as suppressive T regulatory cells are thought to reside within hypoxic niches within the tumour microenvironment that would be amenable to targeting by TH-302.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TH-302 | Experimental | Drug: TH-302480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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 Regional Ethics Board/Independent Ethics Committee (REB/IEC)
- Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent or metastatic and is not curable by surgical or other means.
- Adequate tumour tissue (greater than 0.5cm3 preferred, 3 X core biopsy acceptable) available and agreement from subjects that this tissue from their primary and/or metastatic tumour be made available for assessment of potential biomarkers.
- Ability and availability to complete all prescribed biomarker studies (Screening and after Cycle 2).
Key exclusion criteria (16 listed)
- Anticancer treatment with radiation therapy, targeted therapies, chemotherapy, immunotherapy, hormones or other antitumour therapies within 28 days prior to first dose of TH-302.
- Subjects who have received any other investigational drug or agent within 28 days of first dose of TH-302
- Current use of drugs with known cardiotoxicity
- Significant cardiac dysfunction:
- Seizure disorders requiring anticonvulsant therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TH-302480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle. | Drug | TH-302 |
Primary outcome
Overall Survival
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tillman Pearce, MD study director
Threshold Pharmaceuticals
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TH-302 in people with Metastatic Melanoma, run by ImmunoGenesis at 7 sites in 2 countries.
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 14 inclusion and 16 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: stopped early, as of the sponsor's last update on 11 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 7 sites in Canada, 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 phase mean?
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 16 Aug 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?
Overall Survival (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 May 2025.