Metastatic Melanoma Clinical Trial
Official title:
A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
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.
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. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT02224781 -
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT05470283 -
Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma
|
Phase 1 | |
Recruiting |
NCT05388877 -
E6201 and Dabrafenib for the Treatment of Central Nervous System Metastases From BRAF V600 Mutated Metastatic Melanoma
|
Phase 1 | |
Active, not recruiting |
NCT05103891 -
Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations
|
Phase 1 | |
Completed |
NCT00414765 -
Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
|
Phase 4 | |
Completed |
NCT02857270 -
A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
|
Phase 1 | |
Completed |
NCT01621490 -
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
|
Phase 1 | |
Recruiting |
NCT05779423 -
Cryoablation+Ipilimumab+Nivolumab in Melanoma
|
Phase 2 | |
Active, not recruiting |
NCT04940299 -
Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
|
Phase 2 | |
Active, not recruiting |
NCT02278887 -
Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma
|
Phase 3 | |
Active, not recruiting |
NCT02360579 -
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT02521870 -
A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
|
Phase 1/Phase 2 | |
Completed |
NCT02177110 -
A Translational Systems Medicine Approach to Provide Predictive Capacity for Therapy Response in Advanced or Metastatic Malignant Melanoma
|
||
Withdrawn |
NCT01340729 -
Open-Label Study of TPI 287 for Patients With Metastatic Melanoma
|
Phase 1/Phase 2 | |
Withdrawn |
NCT01416844 -
Study of Immune Responses in Patients With Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT01468818 -
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00984464 -
Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
|
Phase 2 | |
Completed |
NCT00631618 -
Clinical Trial of Sutent to Treat Metastatic Melanoma
|
Phase 2 | |
Terminated |
NCT00571116 -
Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
|
Phase 1 | |
Recruiting |
NCT00226473 -
Standard Palliative Care Versus Standard Palliative Care Plus Polychemotherapy in Metastasized Malignant Melanoma
|
Phase 4 |