Phase II Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer

Пили, Роберто; Häggman, Michael; Stadler, Walter M.; Gingrich, Jeffrey R.; Assikis, Vasileios; Björk, Anders; Nordle, Örjan; Forsberg, G.; Carducci, Michael A.; Armstrong, Andrew J.

doi:10.1200/jco.2011.35.6295

Cited by 193 publications

(154 citation statements)

References 24 publications

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“…These compounds have shown efficacy in several mouse models of inflammatory autoimmune disease [29][30][31][32][33] and they are currently in clinical development for multiple sclerosis [34][35][36][37], systemic sclerosis and prostate cancer [38,39]. Recently, the S100A9 protein was identified as one molecular target of the Q-compound paquinimod (ABR-215757) [40].…”

Section: Introductionmentioning

confidence: 99%

The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects

Deronic

Helmersson

Leanderson

et al. 2014

International Immunopharmacology

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Section: Introductionmentioning

confidence: 99%

The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects

Deronic

Helmersson

Leanderson

et al. 2014

International Immunopharmacology

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“…These patients could also be enrolled in clinical trials with drugs that target HIF1a function (e.g. tasquinimod and other agents that target HIF1a or its downstream products) [34][35][36][37]. Present findings should be further extended and replicated by future studies focusing on genetic polymorphisms as predictors of treatment response to allow tailored therapy in PCa patients.…”

Section: Discussionmentioning

confidence: 86%

The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration

Fraga

Ribeiro

Príncipe

et al. 2014

European Journal of Cancer

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KEYWORDS Androgen deprivation therapy Hypoxia inducible factor 1 alpha Metastasis Prostate cancer Single nucleotide polymorphismAbstract The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT.

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“…For these eight successful phase 3 trials, there were nine preceding phase 2 trials [44][45][46][47][48][49][50][51][52]. For the 23 failed phase 3 trials there were 20 preceding phase 2 trials [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] (Table 1b). Trials were published from January 1994 to April 2017.…”

Section: Trial Characteristicsmentioning

confidence: 99%

Can RECIST response predict success in phase 3 trials in men with metastatic castration-resistant prostate cancer?

Brown

Sonpavde

Armstrong

2018

Prostate Cancer Prostatic Dis

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Background Intermediate endpoints are needed in early phase studies of men with metastatic castration-resistant prostate cancer (mCRPC) that can reliably predict success in phase 3 trials. Among men with measurable disease, objective response may provide information as to whether a treatment is likely to be successful. Methods We conducted a systematic review of systemic agents that have proceeded to phase 3 trials in men with mCRPC and examined the relationship between improvements in measurable disease response in phase 2 trials and successful phase 3 trials leading to regulatory approval. Only trials that included men with radiographically measurable disease were included. Results We examined 31 eligible mCRPC phase 3 trials between 1992 and 2017 and 29 of the preceding phase 2 trials for RECIST responses. Measurable tumor responses in phase 2 trials were higher for successful therapies in phase 3 trials in chemotherapy-naive men with mCRPC, but were less correlated with success in trials investigating docetaxel combination regimens or the post chemotherapy mCRPC setting. Many failed agents did not produce higher than expected response rates over control arms; however, several agents such as anti-angiogenic therapies or orteronel produced higher than expected responses without survival benefit. Conclusions Objective responses in men with mCRPC may be associated with prolonged survival, but this association is mechanism dependent and inconsistent across trials or disease states. These data support considering RECIST response as a supportive but not sole endpoint in phase 2 trials to support launching phase 3 trials.

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Phase II Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer

Abstract: TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.

Cited by 193 publications

References 24 publications

The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects

The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects

The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration

Can RECIST response predict success in phase 3 trials in men with metastatic castration-resistant prostate cancer?

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