A Phase III Randomized Study of BBI608 and Best Supportive Care Versus Placebo and Best Supportive Care in Patients With Pretreated Advanced Colorectal Carcinoma
The purpose of this study is to find out whether it is better to receive a new drug, BBI608, or better to receive no further treatment for colon or rectal cancer. To do this, half of the patients in this study will get BBI608 and the other half will receive a placebo (a substance that is designed not to do anything).
Adjuvant Pegylated-Interferon-alpha2b (SylatronTM) for 2 Years Versus Observation in Patients With an Ulcerated Primary Cutaneous Melanoma With T(2-4)bN0M0: a Randomized Phase III Trial of the EORTC Melanoma Group.
Patients with an ulcerated melanoma with Breslow >1 mm, N0M0 have a significantly higher risk for relapse than patients with a non-ulcerated primary and about a 40-50% chance of developing stage IV disease to which they will almost invariably succumb. In stage I and II patients with an ulcerated primary who have been sentinel node (SN-staged) and found to be SN-negative there is still a 25-30% relapse risk. The purpose of this study is to evaluate the effectiveness and safety when treated with PEG IFN alfa-2b for 2 years as compared to observation (no treatment), administered after adequate surgery has been performed for ulcerated primary cutaneous melanomas.
Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29
1区 · 医学
作者: Laurie, S. A. ; Solomon, B. J. ; Seymour, L. ; Ellis, P. M. ; Goss, G. D. ; Shepherd, F. A. ; Boyer, M. J. ; Arnold, A. M. ; Clingan, P. ; Laberge, F. ; Fenton, D. ; Hirsh, V. ; Zukin, M. ; Stockler, M. R. ; Lee, C. W. ; Chen, E. X. ; Montenegro, A. ; Ding, K. ; Bradbury, P. A.
This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer.
Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70.
The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia.
The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.
2012-01-01·OncoTargets and Therapy4区 · 医学
Targeted agents for the treatment of metastatic melanoma
4区 · 医学
作者: Monzon, Jose G. ; Dancey, Janet
In the last year, the armamentarium of melanoma therapeutics has radically changed. Recent discoveries in melanoma biology and immunology have led to novel therapeutics targeting known oncogenes and immunotherapeutic antibodies. Phase III clinical trials of these agents have reported measurable and meaningful benefits to patients with metastatic disease. In this article, we review recent findings and discuss their significance in melanoma therapy. As our understanding of melanoma biology grows, this initial therapeutic success may be enhanced through the use of molecular markers to select patients, and new targeted immunotherapies in sequential or combination drug regimens.
2010-03-15·Clinical Cancer Research1区 · 医学
The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee
1区 · 医学
作者: Seymour, Lesley ; Ivy, S. Percy ; Sargent, Daniel ; Spriggs, David ; Baker, Laurence ; Rubinstein, Larry ; Ratain, Mark J. ; Le Blanc, Michael ; Stewart, David ; Crowley, John ; Groshen, Susan ; Humphrey, Jeffrey S. ; West, Pamela ; Berry, Donald
The optimal design of phase II studies continues to be the subject of vigorous debate, especially studies of newer molecularly targeted agents. The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials, further emphasize the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force (CTD-TF) of the National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate, such as endpoints (response versus progression-free survival), randomization (single-arm designs versus randomization), inclusion of biomarkers, biomarker-based patient enrichment strategies, and statistical design (e.g., two-stage designs versus multiple-group adaptive designs). Although these recommendations in general encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs, we acknowledge that objective response as an endpoint and single-arm designs remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation.
With Monkeypox, COVID-19, and subsequent Long COVID symptoms in addition to persistent diseases like cancer and Alzheimer's, the world is dealing with a lot right now. Luckily, the pharmaceutical world has clinical trials underway to address all of them.
SIGA Technologies' product TPOXX (tecovirimat), an antiviral approved in the U.S. for smallpox, is being used under certain conditions for monkeypox, but only under “compassionate use” in the U.S. The NIH is now involved in developing a U.S.-based randomized clinical trial to evaluate the drug for the treatment of monkeypox disease, which will be conducted by the AIDS Clinical Trials Group.
SyneuRx International announced results from its Phase II trial of SNB01 (pentarlandir), a novel COVID-19 oral antiviral candidate. The trial evaluated 89 patients who had breakthrough or unvaccinated cases of COVID-19 and were given high-dose, low-dose or placebo. Pantarlandir decreased the inflammation caused by the disease and improved overall health. Pantarlandir blocks coronavirus replication.
CymaBay Therapeutics completed enrollment for its Phase III RESPONSE study of seladelpar for Primary Biliary Cholangitis (PBC). The study is evaluating the safety and efficacy of the drug for patients with PBC who have been using ursodeoxycholic acid (UDCA or ursodial) but have not achieved the recommended treatment goal, or who can’t tolerate UDCA. Seladelpar is a first-in-class oral, selective PPAR delta agonist.
Eliem Therapeutics reported results from its Phase IIa trial of ETX-810 for lumbosacral radicular pain (LSRP). ETX-810 is a new entity prodrug of the bioactive lipid palmitoylethanolamide (PEA). It is also being evaluated in diabetic peripheral neuropathic pain (DPNP). The study did not achieve statistically signification separation from placebo on the study’s primary endpoint, which was changed from baseline to week 4 in the weekly average of the daily pain score measured with the Pain Intensity Numerical Rating Scale (PI-NRS). This was consistent with the Phase IIa study of the drug in DPNP. As a result, they are discontinuing the development of the drug.
Immutep presented new data from its Phase II TACTI-002 trial of eftilagimod alpha for first-line treatment of non-small cell lung cancer (NSCLC). The study hit the primary objective, with an overall response rate (ORR) of 38.6% to the combination of the drug with Merck’s Keytruda (pembrolizumab) and favorable anti-tumor activity. There were also improved secondary endpoints, including Disease Control Rate (DCR) and interim median Progression Free Survival (PFS), across all PD-L1 expression levels. The drug is a soluble LAG-3 fusion protein.
Orca Bio announced its Phase III Precision-T trial is open, enrolling and treating patients. It expects to enroll about 174 patients at more than 20 transplant centers across the U.S. It is studying the safety and efficacy of Orca-T compared to standard-of-care allogeneic hematopoietic stem cell transplant. Orca-T is an investigational high-precision cell therapy made up of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors.
Halozyme Therapeutics announced Roche’s Phase III IMscin001 trial of a subcutaneous formulation of Tecentriq (atezolizumab) with Halozyme’s ENHANZE technology met its co-primary endpoints. The study demonstrated non-inferior levels of Tecentriq in the blood when injected SC compared with IV infusion in cancer immunotherapy-naïve patients with locally advanced or metastatic NSCLC where previous platinum therapy failed.
Landos Biopharma announced positive topline data from its Phase Ib trial of NX-13 for ulcerative colitis. The drug is a novel, oral, NLRX1 agonist, dosed once a day for four weeks. The drug was well tolerated. The company plans to initiate a Phase II trial to evaluate the safety, efficacy, and optimal dosing.
Athira Pharma presented the first results from its Phase II proof-of-concept trial of fosgonimeton in mild-to-moderate Alzheimer’s. The drug is a small-molecule positive modulator of the HGF/MET neurotrophic factor system. The primary outcome analysis (mITT, MMRM) did not meet statistical significance. However, the company indicates the data gave meaningful insights into the drug’s potential effects, including showing its potential activity, which included a decrease in plasma levels of the fluid biomarker, NfL.
Novavax initiated a Phase IIb/III Hummingbird trial to evaluate two doses of its COVID-19 vaccine in younger children ages 6 months through 11 years, followed by a booster at 6 months after the primary vaccination series. The study is expected to enroll 3,600 children in the U.S., Mexico, Colombia, Argentina, Spain, UK, South Africa, the Philippines and Brazil.