Melanoma tissue samples from a clinical trial: no treatment vs. post-temsirolimus alone vs. post-combination temsirolimus and bevacizumab
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Wagenseller Aubrey
PROVIDER: S-ECPF-GEOD-37131 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:To determine if treatment with a combined therapeutic regimen, which resulted in clinical benefit in a subset of patients in a clinical trial, alters miRNA expression in a way that may be used to guide treatment with these agents and to identify miRNAs that may be involved in the mechanism of action of this regimen
2013-03-08 | GSE37131 | GEO
Project description:To determine if treatment with a combined therapeutic regimen, which resulted in clinical benefit in a subset of patients in a clinical trial, alters miRNA expression in a way that may be used to guide treatment with these agents and to identify miRNAs that may be involved in the mechanism of action of this regimen Three-condition experiment, untreated tissue, post-temsirolimus alone treatment, post combination-treatment tissue. 33 total samples, including 5 samples resubmitted for quality control.
2013-03-08 | E-GEOD-37131 | biostudies-arrayexpress
Project description:Purpose:To evaluate the efficacy of three intravitreal bevacizumab (IVB) injections versus the same combined with 2% of topical dorzolamide in the treatment of diabetic macular edema (DME). Methods:In this randomized double-masked clinical trial, 32 eyes of 16 treatment-naive patients with bilateral DME were enrolled. The eyes were randomly assigned to receive three monthly injections of IVB (1.25?mg) plus topical dorzolamide 2% twice daily or IVB (1.25?mg) plus topical artificial tear twice daily. Best-corrected visual acuity (BCVA) was the primary outcome of the study followed by the central macular thickness (CMT) and central macular volume (CMV) as the secondary outcomes. Results:Mean BCVA changes were insignificant in both groups. It changed from 0.21?±?0.08 logMAR at baseline to 0.23?±?0.09 (P=0.24) in the combination group and from 0.18?±?0.09 logMAR to 0.21?±?0.09 (P=0.11) in the IVB alone group, at 3 months, respectively. Changes in mean CMT and CMV were significant in both groups. However, the difference between the groups was not significant at all the visits. In the study, no major ocular complication or systemic side effects were noted regarding IVB or topical dorzolamide. Conclusion:This randomized contralateral clinical trial demonstrated that adjuvant topical dorzolamide with IVB injection had no additional effects on IVB in the treatment of DME over a three-month course. This trial is registered with the Iranian Registry of Clinical Trials under the registration code IRCT20131229015975N5.
| S-EPMC6988687 | biostudies-literature
Project description:ImportanceCytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade with ipilimumab prolongs survival in patients with metastatic melanoma. CTLA-4 blockade and granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine combinations demonstrate therapeutic synergy in preclinical models. A key unanswered question is whether systemic GM-CSF (sargramostim) enhances CTLA-4 blockade.ObjectiveTo compare the effect of ipilimumab plus sargramostim vs ipilimumab alone on overall survival (OS) in patients with metastatic melanoma.Design, setting, and participantsThe Eastern Cooperative Oncology Group (ECOG) conducted a US-based phase 2 randomized clinical trial from December 28, 2010, until July 28, 2011, of patients (N = 245) with unresectable stage III or IV melanoma, at least 1 prior therapy, no central nervous system metastases, and ECOG performance status of 0 or 1.InterventionsPatients were randomized to receive ipilimumab, 10 mg/kg, intravenously on day 1 plus sargramostim, 250 μg subcutaneously, on days 1 to 14 of a 21-day cycle (n = 123) vs ipilimumab alone (n = 122). Ipilimumab treatment included induction for 4 cycles followed by maintenance every fourth cycle.Main outcomes and measuresPrimary end point: comparison of length of OS. Secondary end point: progression-free survival (PFS), response rate, safety, and tolerability.ResultsMedian follow-up was 13.3 months (range, 0.03-19.9). Median OS as of December 2012 for ipilimumab plus sargramostim was 17.5 months (95% CI, 14.9-not reached) vs 12.7 months (95% CI, 10.0-not reached) for ipilimumab. The 1-year survival rate for ipilimumab plus sargramostim was 68.9% (95% CI, 60.6%-85.5%) compared to 52.9% (95% CI, 43.6%-62.2%) for ipilimumab alone (stratified log-rank 1-sided P = .01; mortality hazard ratio 0.64 [1-sided 90% repeated CI, not applicable-0.90]). A planned interim analysis was conducted at 69.8% of expected events (104 observed with 149 expected deaths). Planned interim analysis using the O'Brien-Fleming boundary was crossed for improvement in OS. There was no difference in PFS. Median PFS for ipilimumab plus sargramostim was 3.1 months (95% CI, 2.9-4.6) vs 3.1 months (95% CI, 2.9-4.0) for ipilimumab alone. Grade 3 to 5 adverse events occurred in 44.9% (95% CI; 35.8%-54.4%) of patients in the ipilimumab plus sargramostim group vs 58.3% (95% CI, 49.0%-67.2%) of patients in the ipilimumab-alone group (2-sided P = .04).Conclusion and relevanceAmong patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone resulted in longer OS and lower toxicity, but no difference in PFS. These findings require confirmation in larger studies with longer follow-up.Trial registrationclinicaltrials.gov Identifier: NCT01134614.
| S-EPMC4336189 | biostudies-literature
Project description:BackgroundThis phase I/II trial in patients with recurrent glioblastoma (GBM) evaluates the safety and preliminary efficacy of marizomib, an irreversible pan-proteasome inhibitor that crosses the blood-brain barrier.MethodsPart A assessed the safety and efficacy of marizomib monotherapy. In Part B, escalating doses of marizomib (0.5-0.8 mg/m2) in combination with bevacizumab were evaluated. Part C explored intra-patient dose escalation of marizomib (0.8-1.0 mg/m2) for the combination.ResultsIn Part A, 30 patients received marizomib monotherapy. The most common AEs were fatigue (66.7%), headache (46.7%), hallucination (43.3%), and insomnia (43.3%). One patient (3.3%) achieved a partial response. In Part B, the recommended phase II dose of marizomib was 0.8 mg/m2 when combined with bevacizumab 10 mg/kg. In Part C, dose escalation to 1.0 mg/m2 was not tolerated. Pooled analysis of 67 patients treated with marizomib ≤0.8 mg/m2 and bevacizumab showed a nonoverlapping safety profile consistent with the known safety profile of each agent: the most common grade ≥3 AEs were hypertension (16.4%), confusion (13.4%), headache (10.4%), and fatigue (10.4%). The overall response rate was 34.3%, including 2 patients with complete response. Six-month progression-free survival was 29.8%; median overall survival was 9.1 months.ConclusionsThe safety profile of marizomib as monotherapy and in combination with bevacizumab was consistent with previous observations that marizomib crosses the blood-brain barrier. Preliminary efficacy did not demonstrate a meaningful benefit of the addition of marizomib to bevacizumab for the treatment of recurrent GBM.
| S-EPMC8557653 | biostudies-literature
Project description:ImportanceClinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children.ObjectiveTo determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema.Design, setting, and participantsThis multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017.InterventionsParticipants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation.Main outcomes and measuresThe primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost.ResultsOf the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths.Conclusions and relevanceThe addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema.Trial registrationClinicalTrials.gov identifier: NCT01717742.
| S-EPMC7042898 | biostudies-literature
Project description:PurposeA CTEP-sponsored phase II trial was conducted to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma.Experimental designPatients with unresectable stage III to IV melanoma were treated intravenously with temsirolimus 25 mg weekly and bevacizumab 10 mg every 2 weeks. Adverse events were recorded using CTCAE v3.0. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and overall survival was recorded. Correlative studies measured protein kinases and histology of tumor biopsies and immune function in peripheral blood.ResultsSeventeen patients were treated. Most patients tolerated treatment well, but 2 had grade 4 lymphopenia and 1 developed reversible grade 2 leukoencephalopathy. Best clinical response was partial response (PR) in 3 patients [17.7%, 90% confidence interval (CI) 5, 0-39.6], stable disease at 8 weeks (SD) in 9 patients, progressive disease (PD) in 4 patients, and not evaluable in 1 patient. Maximal response duration for PR was 35 months. Ten evaluable patients had BRAF(WT) tumors, among whom 3 had PRs, 5 had SD, and 2 had PD. Correlative studies of tumor biopsies revealed decreased phospho-S6K (d2 and d23 vs. d1, P < 0.001), and decreased mitotic rate (Ki67(+)) among melanoma cells by d23 (P = 0.007). Effects on immune functions were mixed, with decreased alloreactive T-cell responses and decreased circulating CD4(+)FoxP3(+) cells.ConclusionThese data provide preliminary evidence for clinical activity of combination therapy with temsirolimus and bevacizumab, which may be greater in patients with BRAF(wt) melanoma. Mixed effects on immunologic function also support combination with immune therapies.
| S-EPMC3700572 | biostudies-literature
Project description:To simulate clinical trials to assess overall survival (OS) benefit of bevacizumab in combination with chemotherapy in selected patients with gastric cancer (GC), a modeling framework linking OS with tumor growth inhibition (TGI) metrics and baseline patient characteristics was developed. Various TGI metrics were estimated using TGI models and data from two phase III studies comparing bevacizumab plus chemotherapy vs. chemotherapy as first-line therapy in 976 GC patients. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, Eastern Cooperative Oncology Group (ECOG) score, albumin level, and Asian ethnicity were significant covariates in the final OS model. The model correctly predicted a decreased hazard ratio favorable to bevacizumab in patients with high baseline plasma VEGF-A above the median of 113.4 ng/L. Based on trial simulations, in trials enrolling patients with elevated baseline plasma VEGF-A (500 patients per arm), the expected hazard ratio was 0.82 (95% prediction interval: 0.70-0.95), independent of ethnicity.
| S-EPMC4961078 | biostudies-literature
Project description:ImportanceSurgical interventions, notably noncultured epidermal suspension (NCES), are the next line of treatment in patients with vitiligo who fail to respond to medical therapy. Noncultured epidermal suspension is usually performed in patients with vitiligo with duration of clinical stability (DS) of 12 months or longer because DS is a vital parameter in determining outcome of NCES. In this pilot study, we planned to assess the efficacy of a novel combination of noncultured epidermal cell suspension and noncultured dermal cell suspension (NCES and NDCS) in patients with vitiligo with shorter DS (3-6 months).ObjectiveTo compare the efficacy of transplantation of NCES and NDCS vs NCES alone in patients with vitiligo with DS of 3 to 6 months.Design, setting, and participantsA single-center randomized clinical trial including 40 patients with focal, segmental, or generalized vitiligo with DS of 3 to 6 months or more than 12 months was carried out. Based on DS, 2 groups including 20 patients each were recruited (DS in group 1, 3 to 6 months; DS in group 2, more than 12 months). Each group was further randomized into 2 subgroups, A and B.InterventionPatients in subgroups 1A and 2A underwent NCES alone, whereas patients in subgroups 1B and 2B underwent NCES and NDCS.Main outcomes and measuresExtent of repigmentation, color match, and pattern of repigmentation at 24 weeks.ResultsOf the 40 study participants, mean (SD) age was 24.9 (4.0) years and 24 (60%) were women; in group 1 with DS for 3 to 6 months, more than 75% repigmentation at 24 weeks was observed in all 10 patients in subgroup 1B (NCES and NDCS) compared with 3 of 10 patients in subgroup 1A (NCES) (100% vs 30%, P = .003). In group 2 (DS > 12 months), the same was observed in 6 of 10 patients in subgroup 2A and 7 of 10 patients in subgroup 2B (NCES) (60% vs 70%, P > .99). The 2 groups and subgroups did not show any significant differences with respect to color matching and pattern of repigmentation.Conclusions and relevanceCombination of NCES and NDCS resulted in excellent response in patients with vitiligo with shorter duration of clinical stability compared with NCES alone. This combination may be used early in the course of stable vitiligo without waiting for a period of 12 months or more since last clinical activity.Trial registrationClinicalTrials.gov identifier: NCT03013049.
| S-EPMC6439545 | biostudies-literature
Project description:BackgroundAbout 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX.Methods/designThe Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life.ConclusionThe HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA.Trial registrationClinicalTrials.gov Identifier NCT00394992.
| S-EPMC2958953 | biostudies-literature