Randomized phase II 8-arm factorial study of adjuvant dose-dense (dd) temozolomide (TMZ) with permutations of thalidomide (Thal), isotretinoin (CRA), and/or celecoxib (Cel) for newly diagnosed glioblastoma (GBM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2003-2003
Author(s):  
Mark R. Gilbert ◽  
Kenneth R. Hess ◽  
Lore Lagrone ◽  
Morris D. Groves ◽  
Victor A. Levin ◽  
...  
Keyword(s):  
Factorial Design ◽  
Phase Ii ◽  
Standard Of Care ◽  
Hepatic Function ◽  
Newly Diagnosed ◽  
Cytostatic Agents ◽  
Current Standard ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
The Impact

2003 Background: Concurrent radiation and TMZ followed by 6-12 months of adjuvant TMZ (d 1-5 of a 28d cycle) is the current standard of care for patients with newly diagnosed GBM. The addition of cytostatic or signal transduction agents may enhance efficacy without a significant increase in toxicity. A phase I trial (Neuro-oncology 2009) established the safety of ddTMZ with 2 or 3 of the cytostatic agents. Methods: This randomized phase II study was conducted by the Brain Tumor Trials Collaborative (BTTC) and the MDACC CCOP. The primary objectives: determine if specific cytostatic agents added to ddTMZ alters outcomes (PFS, OS) and compare triplet with doublet therapy. Eligibility criteria: centrally confirmed newly diagnosed GBM, age ≥18, KPS≥60, stable or improved after chemoradiation (pseudoprogression allowed), adequate hematologic, renal and hepatic function. Pts were randomly assigned to 12 treatment cycles (28 d/cycle) in 8 arms: ddTMZ alone (150 mg/m2/day, 7-d on, 7-d off) or TMZ-containing doublet, triplet and quadruplet combinations with Thal, CRA, or Cel. Results: The study enrolled 155 eligible patients from 11/2005 to 9/2010 to the 8 arms of the factorial design. Median age was 53 (18-84) and median KPS, 90 (60-100). Compared with TMZ alone, the TMZ+CRA doublet had worse PFS (10.5, 6.5 mo; p=0.043) and OS (21.2, 11.7 mo; p=0.037). Trends were also seen for worse outcome (PFS, OS) for CRA-containing regimens, improved OS for Cel containing arms and no impact of Thal. A strong trend for OS improvement was seen for triplet compared with doublet regimens (20.1, 17.0 mo; p=0.15), but no difference for PFS. Treatment was well tolerated with expected high rates of grade 3/4 lymphopenia, and overall a modest toxicity rate. Conclusions: The results indicate that the addition of CRA to ddTMZ may be detrimental in patients with newly diagnosed GBM. This study demonstrated the utility of the factorial design in efficiently testing drug combinations, the impact of individual agents in these combinations as well as doublet vs. triplet regimens and supports its utility in testing combinations of targeted agents.

Intermittent chemotherapy (ICh) for metastatic castration-resistant prostate cancer (mCRPC): Results of a prospective randomized phase II trial of the DoD Prostate Cancer Clinical Trials Consortium.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 133-133
Author(s):  
A. L. Harzstark ◽  
T. M. Beer ◽  
V. K. Weinberg ◽  
C. S. Higano ◽  
L. T. Nordquist ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Standard Of Care ◽  
Patient Choice ◽  
Castration Resistant Prostate Cancer ◽  
Gm Csf ◽  
Randomized Phase Ii ◽  
Intermittent Chemotherapy ◽  
The Impact

133 Background: Docetaxel remains the standard of care for patients (pts) with mCRPC. However, the optimal duration of chemotherapy (Ch) is not known. Providing Ch holidays is often undertaken, but is not well characterized. A randomized phase II trial was undertaken to test two ICh regimens. Methods: Pts with Ch naive mCRPC and KPS > 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m2 q3 weeks, and prednisone 5 mg po bid. After 6 cycles, responding pts (PSAWG1 criteria) stopped Ch and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m2 sq daily for 14 days out of every 28 day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progressive disease (PD) by PSAWG1 criteria, at which point they resumed treatment with Ch, again for 6 cycles, followed by the same “off Ch” regimen. The primary endpoint was the time to PD while on Ch (time to Ch resistance.) Results: Of 97enrolled pts to date, 94 are evaluable (3 are still undergoing induction). 69 pts completed induction (25 did not due to PD, adverse events (AE), or MD choice), of which 27 had PD after 6 cycles. Thus, 42/94 evaluable pts (45%) were eligible for randomization. Of these, 21 pts underwent Obs and 21 received GM-CSF. To date, 23/42 (55%) pts who underwent a Ch holiday restarted Ch, all for PSA PD. 8/23 (35%) had a response to Ch re-initiation. (15 pts did not re-start Ch because of AE, other therapy being started, or patient choice, and 4 pts are still undergoing either Obs or GM-CSF.) Obs pts were “off Ch” for a median of 2 months (range 2-4), compared with 3 months (range 2-8) for GM-CSF pts. Conclusions: While feasible, only 45% of pts met criteria for ICh. 35% of pts responded to Ch re-initiation. Insufficient data exist to assess the impact of GM-CSF on time off Ch or time to Ch resistance. No significant financial relationships to disclose.

VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantion (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 450-450 ◽  
Author(s):  
Jean Luc Harousseau ◽  
Claire Mathiot ◽  
Michel Attal ◽  
Gerald Marit ◽  
Denis Caillot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Standard Of Care ◽  
Response Assessment ◽  
Primary Objective ◽  
Induction Treatment ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Phase Ii Studies ◽  
The Impact

Abstract Introduction. ASCT is considered the standard of care for younger patients (pts) with MM. The benefit of ASCT is at least partly related to an increase in Complete Remission (CR) plus Very Good Partial Remission (VGPR) rate. One way to increase the CR rate is to improve the induction treatment prior to ASCT. Several phase II studies with Vel in combination as induction treatment yielded promising CR rates. We have previously tested the Vel/D combination with Vel 1.3mg/m2 d1,4,8,11 with 40mg/d d1–4, d 9–12 for 4 consecutive 21d cycles (D only on d1–4 during cycles 3–4) (Harousseau et al Haematologica 2006). Methods. In July 2005, the IFM initiated a randomized Phase II trial comparing Vel/D with VAD as induction treatment prior to ASCT in pts with newly diagnosed MM up to the age of 65.This IFM 2005/01 was closed for accrual in January 2007 after having recruited 482 patients. The primary objective was the CR (negative immunofixation) plus n-CR (negative electrophoresis) after 4 cycles. The second question was to evaluate the impact of a consolidation with 2 cycles of DCEP (D, Cyclophosphamide, Etoposide, Platinum). At diagnosis pts were randomized between 4 arms (A1:4 cycles of VAD, A2: 4 cycles of VAD + 2 cycles of DCEP, A3:4 cycles of Vel/D, A4:4 cycles of Vel/D + 2 cycles of DCEP). Randomization was stratified according to β2-microglobulin and del 13 by FISH analysis. Stem cell collection was performed between cycle 3 and 4 after G-CSF priming (10μg/kg x 6d). ASCT was prepared by melphalan 200mg/m2. Results. As of Aug 2007, data from the first consecutively enrolled 222 pts have been analyzed (A1:54,A2:56,B1:55,B2:57). In the VAD arms (A1+A2),88% of pts received the planned 4 courses versus 94% in the Vel/D arms (B1+B2). In arm A2,87.5% of pts received the 2 cycles of DCEP versus 82% in arm B2. ASCT was performed in 94% of evaluable pts in arms A1+A2 and in 92% in arms B1+B2. The number of SAE was the same in the VAD and the Vel/D arms. The incidence of grade 3–4 averse events was also comparable. However the proportion of pts with neurological symptoms (all grades) during induction treatment was higher with Vel/D (36% versus 11%). Response assessment is available for 208 pts (100 VAD, 108 Vel/D). The results are shown in the table (intent-to-treat analysis). Consolidation with DCEP did not increase the CR rate (16% pre-ASCT both in arms A1+B1 and in arms A2+B2). Conclusion. This analysis not only confirms that the post-induction CR rate is increased by Vel/D compared to VAD (Harousseau ASH 2006) but also shows that this benefit translates in higher CR+VGPR rates after ASCT. Longer follow-up is needed to demonstrate that this better tumor reduction induces longer PFS and OS. Currently 1-year PFS and OS rates are respectively 90% and 95% with VAD, 93% and 97% with Vel/D. Updated results will be presented at the meeting.

scholarly journals SYST-08. A phase II trial of concurrent Sunitinib, Temozolomide and Radiation Therapy followed by adjuvant Temozolomide for newly diagnosed Glioblastoma patients with an unmethylated MGMT gene promoter (A01-M121-11A, McG1132)

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv10-iv10
Author(s):  
Mame Daro Faye ◽  
Siham Sabri ◽  
Paula De Robles ◽  
Raman Agnihotram ◽  
Alexander Torres-Vasquez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Standard Of Care ◽  
Treatment Modalities ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Who Grade ◽  
Adjuvant Temozolomide ◽  
Mgmt Promoter ◽  
Grade 3

Abstract INTRODUCTION Despite advances in treatment modalities, the overall prognosis of GBM remains dismal, particularly for patients with unmethylated MGMT promoter. Thus, alternative treatment strategies are warranted. Our group has previously shown that addition of Sunitinib (SU11248) to standard therapy significantly improved the response of unmethylated MGMT cells through decreased angiogenicity and tumorigenicity. In this phase II trial, we tested for the first time the combination of Sunitinib with RT and Temozolomide in newly diagnosed MGMT unmethylated GBM patients. METHODS Patients with histologically confirmed WHO Grade IV GBM and MS-PCR confirmed unmethylated MGMT promoter, age 18-70, KPS ≥70, life expectancy ≥6 months were eligible. 41 patients treated between 2012 and 2017 were screened, 37 of which were eligible. Patients received 12.5 mg of daily Sunitinib for 7 days, followed by concurrent RT, Temozolomide and 12.5 mg Sunitinib for 6 weeks, then adjuvant Temozolomide x6 cycles. RT and Temozolomide doses were as per standard of care. Primary objective was PFS as assessed by RANO criteria, secondary objectives were OS and safety. RESULTS Median follow-up time was 15 months. Median PFS was 7 months (95%CI, 6.7-7.2) and 6-month PFS was 59.3%. Median OS was 13 months (95%CI, 12.62-13.37) and 2-year OS was 17.8%. Two patients had OS >50 months, with one surviving 71 months. Having received >3 cycles of adjuvant Temozolomide, surgery at progression or age ≤65 significantly predicted for better OS, with hazard ratios of 0.184 (p=0.001), 0.402 (p=0.026) and 10.017 (for age >65, p=0.002) respectively. Grade ≥3 thrombocytopenia occurred in 18.9% of patients, grade ≥3 neutropenia in 10.8% and grade ≥3 thromboembolic events in 13.5%. There were no grade 5 evens. CONCLUSION Addition of Sunitinib to RT and Temozolomide was well tolerated and survival outcomes compared favorably to the current standard of care for GBM patients with unmethylated MGMT promoter status.

Olanzapine (OLN) versus aprepitant (APR) in patients receiving high-emetogenic chemotherapy: Final results of randomized phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11504-11504
Author(s):  
Alexey Rumyantsev ◽  
Elena Glazkova ◽  
Rukhshona Nasyrova ◽  
Ekaterina Ignatova ◽  
Lia Chitia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Rescue Medication ◽  
Standard Of Care ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Current Standard ◽  
Randomized Phase Ii ◽  
Radio Therapy ◽  
Oncology Practice ◽  
Practice Methods

11504 Background: Management of chemotherapy-induced nausea and vomiting (CINV) remains challenging. OLN might provide several benefits over APR which is current standard of care – particularly in terms of nausea control and cost effectiveness. However, sedation associated with recommended doses of olanzapine precludes its wide use in oncology practice. Methods: This was randomized phase II single center study aimed to compare OLN and APR in CINV prophylaxis. Key inclusion criteria were: chemo- and radio-therapy naïve patients, planned administration of high-emetogenic chemotherapy (cisplatin, carboplatin AUC≥4, doxorubicin etc). Patients were randomized 1:1 ratio in the following arms: olanzapine 5 QD day 0-4 or aprepitant 125 mg day 1, 80 mg day 2,3. All patients received ondansetron 16 mg day 1 and dexamethasone 8 mg day 1-3. Primary endpoint was complete nausea control (no nausea and no rescue medication) 0-120 hours after chemotherapy. Complete response (no emesis and no rescue medication) was a key secondary end point. Nausea was assessed using MASCC Antiemesis Tool. Sample size: 94 patients to increase nausea control rate from 40 to 70% (α = 0.05; β = 0.80; 10% of estimated data loss). Results: We included in the analysis 93 patients who could be evaluated. The groups were well balanced, median age was 49 years, vast majority of patients (95.6%) were females. The proportion of patients with complete nausea control in OLN and APR groups was 44.2% and 24.0% respectively (RR 2.5; 95% CI 1.04-6.08; p = 0.039). Complete response was achieved in 74.4% and 54.0% patients respectively (RR 2.48; 95% CI 1.026-5.99; p = 0.041). No differences in rates of undesired sedations were detected. Conclusions: Our data suggests superiority of OLN regimen in terms of nausea control. This regimen deserves further investigation. Clinical trial information: NCT03478605.

scholarly journals The Impact of Parkinson’s Disease on Social Communication: An Exploratory Questionnaire Study

2021 ◽  
Author(s):  
Saryu Sharma ◽  
Kimberly Fleck ◽  
Sherri Winslow ◽  
Kathrin Rothermich
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Emotional Expression ◽  
Social Communication ◽  
Standard Of Care ◽  
Pragmatic Language ◽  
Current Standard ◽  
Comprehensive Management ◽  
Pragmatic Skills ◽  
The Impact

Individuals with Parkinson’s Disease (PD) often show breakdown in the interpretation of pragmatic language meaning. However, there is no current standard of care for evaluating social communication dysfunction in PD which affects the persons with PD and their caregivers. Thus, we developed a questionnaire for individuals with PD to evaluate social communication difficulties. Objective: The aim of this study was to develop a questionnaire to demonstrate a need for comprehensive management guidelines for individuals with PD regarding social communication skills. This questionnaire will highlight the areas of deficit for the individuals with PD. Methods: Fifty-one people with self-reported Parkinson’s Disease answered 28 survey questions. These questions pertained to emotional expression and perception, social communication, sarcasm/humor, and pragmatic skills. Exploratory factor analysis and reliability analysis were performed to identify which items loaded onto the desired factor and to check the internal consistency of the items. Results: Persons with PD reported changes in emotional expression and perception, social communication, sarcasm and humor, and pragmatic skills domains post PD diagnosis. No correlations were found between age/time since diagnosis and emotional expression, social communication, sarcasm, and humor.Conclusion: The current study provides evidence that persons with PD experience social communication challenges. Therefore, it is crucial to increase awareness of these deficits in PD to recognize the impact of the disease on social communication.

Randomized Phase II Trial of Docetaxel Plus Thalidomide in Androgen-Independent Prostate Cancer

2004 ◽  
Vol 22 (13) ◽  
pp. 2532-2539 ◽  
Author(s):  
William L. Dahut ◽  
James L. Gulley ◽  
Philip M. Arlen ◽  
Yinong Liu ◽  
Katherine M. Fedenko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Weight ◽  
Phase Ii ◽  
Low Molecular Weight Heparin ◽  
Phase Ii Trial ◽  
Low Molecular Weight ◽  
Randomized Phase Ii ◽  
The Impact ◽  
Docetaxel Group ◽  
Androgen Independent

Purpose Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. Methods Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m2 intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. Results After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P = .32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. Conclusion In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination.

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