scholarly journals Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial

2021 ◽  
pp. 1-13
Author(s):  
Roland Devlieger ◽  
Horst Buxmann ◽  
Giovanni Nigro ◽  
Martin Enders ◽  
Julia Jückstock ◽  
...  
Keyword(s):  
Transmission Rate ◽  
Time Frame ◽  
Potential Effect ◽  
Phase Iii ◽  
Preventive Strategy ◽  
Ethical Challenges ◽  
Open Label ◽  
Cmv Disease ◽  
Congenital Cmv

<b><i>Introduction:</i></b> Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We pre­sent a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. <b><i>Methods:</i></b> CMV-seronegative pregnant women (gestational age [GA] &#x3c;14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered Cytotect®. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. <b><i>Results:</i></b> The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11–35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label Cytotect®. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (<i>p</i> = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. <b><i>Conclusions:</i></b> Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.

Impact of PSMA PET/CT on SRT planning: Preliminary results from the randomized phase III trial NCT03582774.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 30-30
Author(s):  
Jeremie Calais ◽  
Wesley R Armstrong ◽  
Amar Upadhyaya Kishan ◽  
Kiara M Booker ◽  
David Elashoff ◽  
...  
Keyword(s):  
Success Rate ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Preliminary Results ◽  
Volume Delineation ◽  
Psma Pet ◽  
Pet Ct ◽  
The Impact

30 Background: The purpose of this trial is to evaluate the success rate of salvage radiation therapy (SRT) for recurrence of prostate cancer (PCa) after radical prostatectomy with and without planning based on prostate specific membrane antigen (PSMA) positron emission tomography (PET). Methods: This is a multicenter, prospective, randomized, controlled, open-label, Phase 3 clinical imaging trial powered for clinical outcome at 5 years. UCLA is the leading central site in which PSMA PET, clinical follow-up and data management are being done. UCSF was a participating site in which PSMA PET imaging can be done. SRT can be performed anywhere, patients are followed remotely by the UCLA investigators. Patients scheduled for SRT for recurrence after primary prostatectomy and with PSA ≥ 0.1ng/ml at time of enrollment were eligible. Patients were randomized to proceed with standard SRT allowing for any conventional imaging aside from PSMA PET/CT (control arm) or undergo a 68Ga-PSMA-11 PET/CT scan prior to SRT planning (investigational arm). The primary endpoint is the success rate of SRT at 5 years in patients who undergo SRT. We report here the preliminary results of a secondary endpoint: the impact of PSMA PET on SRT planning by comparing the pre-randomization RT plans prospectively obtained on surveys before randomization to the actually delivered RT plans obtained after follow-up. Results: Enrollment of the trial was complete. 193 patients were enrolled from 09.06.2018 to 08.17.2020. 7/90 patients (9%) in the control arm dropped-out the study because they underwent a PSMA PET at another institution, while 1/103 (1%) patients of the intervention arm dropped-out due to COVID-19 related complications. After a median follow-up of 13.3 months (last follow-up date 09/01/2020), delivered RT plans were obtained in 60/83 (72%) and 70/102 (69%) of patients of the control and the PSMA arms, respectively. Median PSA at enrollment was 0.32 ng/ml (IQR 0.17-1.35) and 0.22 ng/ml (IQR 0.14-0.50) in the control and PSMA arms, respectively. There was a change between the intended pre-randomization RT plan and the actually delivered RT plan in 17/60 (28%) and 40/70 (57%) of the patients in the control and PSMA arms, respectively (p = 0.002). SRT was aborted in favor of systemic therapy and/or metastasis directed RT for extra-pelvic M1 disease in 2/60 (3%) and 12/70 (17%) of the control and PSMA arms, respectively (p = 0.17). Dose prescription and/or target volume delineation was changed in 2/60 (3%) and 1/70 (26%) in the control and PSMA arms, respectively (p = 0.001). Conclusions: In this prospective randomized phase 3 study, PSMA PET had an impact on the SRT plan in more than half of the patients. Long-term follow-up will show if the impact of PSMA PET on SRT planning translates into improved outcome or not. Clinical trial information: NCT03582774.

scholarly journals Central radiology assessment of the randomized phase III open-label OVHIPEC-1 trial in ovarian cancer

2020 ◽  
Vol 30 (12) ◽  
pp. 1928-1934
Author(s):  
Simone N Koole ◽  
Leigh Bruijs ◽  
Cristina Fabris ◽  
Karolina Sikorska ◽  
Maurits Engbersen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cancer Index ◽  
Disease Recurrence ◽  
Phase Iii ◽  
Ct Scans ◽  
Recurrence Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Peritoneal Cancer

IntroductionHyperthermic intraperitoneal chemotherapy (HIPEC) improved investigator-assessed recurrence-free survival and overall survival in patients with stage III ovarian cancer in the phase III OVHIPEC-1 trial. We analyzed whether an open-label design affected the results of the trial by central blinded assessment of recurrence-free survival, and tested whether HIPEC specifically targets the peritoneal surface by analyzing the site of disease recurrence.MethodsOVHIPEC-1 was an open-label, multicenter, phase III trial that randomized 245 patients after three cycles of neoadjuvant chemotherapy to interval cytoreduction with or without HIPEC using cisplatin (100 mg/m2). Patients received three additional cycles of chemotherapy after surgery. Computed tomography (CT) scans and serum cancer antigen 125 (CA125) measurements were performed during chemotherapy, and during follow-up. Two expert radiologists reviewed all available CT scans. They were blinded for treatment allocation and clinical outcome. Central revision included Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurements and peritoneal cancer index scorings at baseline, during treatment, and during follow-up. Time to centrally-revised recurrence was compared between study arms using Cox proportional hazard models. Subdistribution models compared time to peritoneal recurrence between arms, accounting for competing risks.ResultsCT scans for central revision were available for 231 patients (94%) during neoadjuvant treatment and 212 patients (87%) during follow-up. Centrally-assessed median recurrence-free survival was 9.9 months in the surgery group and 13.2 months in the surgery+HIPEC group (HR for disease recurrence or death 0.72, 95% CI 0.55 to 0.94; p=0.015). The improved recurrence-free survival and overall survival associated with HIPEC were irrespective of response to neoadjuvant chemotherapy and baseline peritoneal cancer index. Cumulative incidence of peritoneal recurrence was lower after surgery+HIPEC, but there was no difference in extraperitoneal recurrences.ConclusionCentrally-assessed recurrence-free survival analysis confirms the benefit of adding HIPEC to interval cytoreductive surgery in patients with stage III ovarian cancer, with fewer peritoneal recurrences. These results rule out radiological bias caused by the open-label nature of the study.

scholarly journals Oral levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

2019 ◽  
Vol 90 (10) ◽  
pp. 1165-1170 ◽  
Author(s):  
Ammar Al-Chalabi ◽  
Pamela Shaw ◽  
P Nigel Leigh ◽  
Leonard van den Berg ◽  
Orla Hardiman ◽  
...  
Keyword(s):  
Heart Rate ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Lateral Sclerosis

ObjectiveTo evaluate the efficacy and safety of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS). This phase II, randomised, double-blind, placebo-controlled, crossover, three-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60%–90 % of predicted from 11 sites in four countries.MethodsPatients received levosimendan 1 mg daily, 1 mg two times a day or placebo during three 14-day crossover periods and levosimendan 1–2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale-Revised (ALSFRS-R), tolerability and safety.ResultsOf 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being −3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg two times a day (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg two times a day (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events.ConclusionsLevosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. A phase III study to evaluate the longer term effects of oral levosimendan in ALS is ongoing.

Rituximab Therapy after Response to R-CHOP Induction Therapy for Patients with Previously Untreated Indolent Non-Hodgkin’s Lymphoma (NHL): Clinical Outcomes and Pharmacokinetics (PK)

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1295-1295
Author(s):  
Louis Fehrenbacher ◽  
Jonathan A. Polikoff ◽  
Robert Hermann ◽  
Haresh Jhangiani ◽  
Jean Bjerke ◽  
...  
Keyword(s):  
Phase Iii ◽  
Open Label ◽  
Community Based ◽  
Serious Adverse Events ◽  
Residual Concentration ◽  
Ann Arbor ◽  
Grade 3 ◽  
To Receive ◽  
Ongoing Phase

Abstract The addition of rituximab (R) therapy significantly improves PFS in patients with relapsedl/refractory disease responding after CHOP as well as responders after R-CHOP induction (van Oers, 2005). The aim of this study was to assess, in patients with previously untreated indolent NHL, the safety, efficacy and PK of additional R therapy in responders to R-CHOP induction. Between 10/01 and 08/06, 102 patients aged 28–84 (mean 57 yr) yrs with Ann Arbor Stage III (28.4%) or IV (71.6%) indolent NHL were treated on this Phase II single-arm, open-label, multi-center, community-based trial. Baseline LDH and β2 microglobulin were above normal in 20.6% and 66.3% of patients, respectively. Treatment consisted of 6 cycles of R-CHOP (cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, and doxorubicin 50 mg/m2 all IV on Day 1 of each 21-day cycle; prednisone 100 mg/d po Days 1–5; and R 375 mg/m2 IV 2–3 days prior to first dose of CHOP and thereafter on Day 1 of each cycle). Patients with ongoing response (CR/CRu or PR) received R 375 mg/m2 weekly x 4, repeated every 6 months x 2 yrs, for a total of up to 16 R doses, within 28 days after completion of R-CHOP. Median follow-up was 39 mos. ORR after R-CHOP was 86.3% (95% CI: 78.3, 92.1), with CR/CRu 48% (95% CI: 38.0, 58.2). As measured from initiation of R-CHOP, PFS at 2 and 3 yrs was 75.2% (95% CI: 64.0, 83.3) and 67.3% (95% CI: 54.6, 77.2), respectively. OS at 2 and 3 yrs was 92.9% (95% CI: 85.7, 96.6) and 89.4% (95% CI: 81.2, 94.2), respectively. Infusion-related toxicity with R given after R-CHOP was less frequent than seen with R-CHOP in this study. The overall incidence of serious adverse events during R therapy given after R-CHOP was 8.5%, including 3 NCI-CTC grade 3/4 events: viral encephalitis (n=1), patellar fracture (n=1) & development of colon cancer (n=1). Serum R concentrations were collected over serial timepoints from 12 patients. Both pre- and end of infusion serum R concentrations were similar across cycles 2–4 of R therapy given after R-CHOP. R concentration was higher just prior to infusion of the first R dose given after R-CHOP due to residual concentration from the R-CHOP treatment. Concentrations were very low (< 10 ug/mL) just prior to initiation of the subsequent R cycles. During R therapy given after R-CHOP, serum R concentrations were similar to those previously reported during R monotherapy treatment (Berinstein, 1998). In summary, this study demonstrated that R therapy given after R-CHOP to be generally well-tolerated, and associated with 75.2% PFS and 92.9% OS at 2 yrs, and 67.3% PFS and 89.4% OS at 3 yrs. Moreover, the current study demonstrates that PK data from R induction can be extrapolated to R given after R-CHOP. The benefit of adding additional R therapy to responders to R-chemotherapy will be addressed in the analysis of the ongoing Phase III PRIMA study, wherein patients with advanced follicular lymphoma who respond to R-chemotherapy induction are randomized to receive further R therapy vs. observation.

A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Lynn Mara Schuchter ◽  
Lawrence E. Flaherty ◽  
Omid Hamid ◽  
Gerald P. Linette ◽  
Sigrun Hallmeyer ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Response Rate ◽  
Phase Iii ◽  
Open Label ◽  
Expanded Access ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Prior Systemic Therapy ◽  
Ecog Ps

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

scholarly journals P231 B-cell depletion therapy with rituximab in RA: UCLH/UCL 20 years of experience

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Caitlin M Norris-Grey ◽  
Samantha Moore ◽  
Geraldine Cambridge ◽  
Venkat Reedy ◽  
Maria Leandro
Keyword(s):  
B Cell ◽  
Service Evaluation ◽  
Cell Depletion ◽  
Phase Iii ◽  
Tender Joint Count ◽  
B Cell Depletion ◽  
Concomitant Therapy ◽  
Open Label ◽  
Tender Joint

Abstract Background B-cell depletion therapy based on rituximab in patients with seropositive rheumatoid arthritis (RA) was pioneered at UCLH/UCL in 1998. The positive results of the initial open-label UCLH/UCL trials led to the Phase IIa proof of concept trial confirming efficacy and safety for rituximab in the treatment of patients with RA. A Phase III trial followed and licensing in 2006. We report a service evaluation of the UCLH/UCL cohort of RA patients treated with rituximab over the last 20 years. Methods A retrospective review of electronic records from all patients with RA treated with rituximab followed up in a dedicated clinic at UCLH/UCL (1998-2019) were included. Data on gender, age at first treatment, previous DMARDs, concomitant therapy at the time of the first rituximab cycle, total number of rituximab cycles and length of follow-up while on rituximab were collected. For patients currently on rituximab, further information was collected at last follow-up, including concomitant therapy, swollen and tender joint count, global VAS, CRP and ESR. DAS28ESR was calculated. Results 296 patients had received rituximab therapy since November 1998, with 105 remaining on rituximab at final data collection (14/10/2019). Median follow-up was 77.5 months. Clinical data is shown in Table 1. Information for previous DMARDs was only available for 196 patients in the whole cohort, and for 70 patients currently on rituximab. The most common concomitant DMARD at first cycle was methotrexate with a similar percentage receiving methotrexate at last follow-up. The median number of previous DMARDs were 4 and 3 respectively. Within both cohorts approximately 31% of patients received rituximab as their first biologic. Conclusion This retrospective service evaluation of 296 patients with RA who had undergone rituximab therapy since 1998 showed that more than one third remained on rituximab at last follow-up. Of these, 70.2% of patients were in clinical remission or with low disease activity. Most patients (94%) remaining on rituximab were receiving only 1 or no concomitant therapies. Multiple cycles of treatment with rituximab have thus proved to be an effective therapeutic strategy for patients with RA resulting in long-term and highly favourable control of their disease. Disclosures C.M. Norris-Grey None. S. Moore None. G. Cambridge None. V. Reedy None. M. Leandro Consultancies; Genentech: consultancy fees for attending meeting on obinutuzumab trial in lupus nephritis.

Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAFV600E-mutated melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8502-8502 ◽  
Author(s):  
Paul B. Chapman ◽  
Axel Hauschild ◽  
Caroline Robert ◽  
James M. G. Larkin ◽  
John B. A. G. Haanen ◽  
...  
Keyword(s):  
Braf Inhibitor ◽  
Final Analysis ◽  
Multicenter Trial ◽  
Data Safety Monitoring Board ◽  
Phase Iii ◽  
Open Label ◽  
Response Data ◽  
Primary Endpoints ◽  
Unresectable Stage

8502^ Background: We previously reported results of the planned OS interim analysis for BRIM-3 (50% of the planned 196 deaths required for final analysis) at which time the independent Data Safety Monitoring Board recommended release of results due to compelling efficacy (hazard ratio [HR] for death, 0.37 [95% CI 0.26–0.55]); p<0.0001 and PFS HR 0.26 [95% CI 0.20–0.33]; p<0.0001) and that DTIC-treated patients be permitted to cross over to receive vem. Median follow-up for vem patients was 3.75 months, and longer follow-up would estimate median OS more reliably. Updated OS with median 6.2 months follow-up and 199 total deaths showed HR for death 0.44 (95% CI 0.33–0.59) favoring vem and median OS for vem not reached. We report here the results of an updated OS analysis performed in Nov 2011 with ~10 months median follow-up on vem. Methods: 675 patients with previously untreated, unresectable Stage IIIC or IV melanoma that tested positive for BRAFV600E mutation by the cobas 4800 BRAF V600 Mutation Test were randomized (1:1) from Jan to Dec 2010 to vem (960 mg po bid) or DTIC (1000 mg/m2 IV q3w). Co-primary endpoints were OS and PFS. OS data for DTIC patients who crossed over to vem were censored at the time of crossover. Results: Median lengths of follow-up on vem and DTIC were 10.5 months (range 0.4–18.1) and 8.4 months (range <0.1–18.3), respectively. There were 334 deaths. Median OS rates with vem and DTIC were 13.2 months (95% CI 12.0–15.0) and 9.6 months (95% CI 7.9–11.8), respectively. 12-month OS rates were 55% for vem and 43% for DTIC. HR for death was 0.62 (95% CI 0.49–0.77) in favor of vem. 81 DTIC patients crossed over to vem. 44 (13%) vem and 65 (19%) DTIC patients received ipilimumab post-progression. Conclusions: With longer follow-up, vem treatment continues to be associated with improved OS in the BRIM-3 study. An updated analysis, with estimated median follow-up of ~13 months and including response data, will be conducted in Apr 2012 and presented at the meeting.

DeCIDE: A phase III randomized trial of docetaxel (D), cisplatin (P), 5-fluorouracil (F) (TPF) induction chemotherapy (IC) in patients with N2/N3 locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Ezra E. W. Cohen ◽  
Theodore Karrison ◽  
Masha Kocherginsky ◽  
Chao H Huang ◽  
Mark Agulnik ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Survival Rates ◽  
Phase Iii ◽  
High Survival ◽  
Open Label ◽  
Free Survival ◽  
Prior Therapy ◽  
Distant Failure ◽  
Grade 3

5500 Background: IC is associated with lower distant failure (DF) rates in SCCHN but an improvement in overall survival (OS) has not been validated. The goal of this trial was to determine whether IC prior to chemoradiotherapy (CRT) improves survival compared to CRT alone. Methods: In this phase 3, open-label trial, subjects with pathologically confirmed SCCHN; N2/N3 disease without metastases; no prior therapy; KPS ³ 70%; and intact organ function were randomized to CRT alone (CRT arm) [5 days of D (25 mg/m2), F (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9 day break] or to 2 cycles of IC [D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)] followed by the same CRT (IC arm). Primary endpoint was OS. Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival (RFS). 280 subjects provided 80% power to detect a hazard ratio HR=0.5 for OS (a=0.05). Results: 280 subjects were accrued from 2004-09 with minimum follow-up 24 months. Of 142 patients randomized to IC, 91% received 2 cycles and 87% continued to CRT. Treatment adherence during CRT was high for docetaxel and hydroxyurea, but fewer than 75% of the patients received target dose of 5FU in both arms. RT was delivered without major deviations in 94% and 95% of patients on IC and CRT arms, respectively. The most common grade 3-4 toxicities during IC were febrile neutropenia (9%) and mucositis (8%), and during CRT (both arms combined) they were mucositis (45%), dermatitis (19%), and leukopenia (17%). Only grade 3-4 leukopenia and neutropenia rates were significantly higher in IC (p=0.002 and p=0.02, respectively). Table shows efficacy. Conclusions: High survival rates were observed in both arms. Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS. [Table: see text]

Australasian Gastrointestinal Trials Group (AGITG) CONTROL NET Study: Phase II study evaluating the activity of 177Lu-Octreotate peptide receptor radionuclide therapy (LuTate PRRT) and capecitabine, temozolomide CAPTEM)—First results for pancreas and updated midgut neuroendocrine tumors (pNETS, mNETS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4608-4608
Author(s):  
Nick Pavlakis ◽  
David Turner Ransom ◽  
David Wyld ◽  
Katrin Marie Sjoquist ◽  
Rebecca Asher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Tumour Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Relative Activity ◽  
Phase Iii ◽  
Study Phase ◽  
Open Label ◽  
Who Grade

4608 Background: CAPTEM is an accepted regimen for patients (pts) with advanced pNETs. Single agent 177Lu-Octreotate PRRT is now a standard of care for progressive WHO Grade (G) 1/2 mNETs. High activity was seen with LuTate/CAPTEM in a single arm Phase I/II trial. This study was undertaken to determine the relative activity of adding CAPTEM to LuTate PRRT in pts with mNETs and pNETs. Methods: Non-comparative randomised open label parallel group phase II trial with 2:1 randomisation to PRRT/CAPTEM (experimental arm) vs. PRRT (mNETs control) and CAPTEM (pNETS control). PRRT/CAPTEM: 7.8GBq LuTate day(D) 10, 8 weekly (wkly) x 4, with b.i.d. oral CAP 750mg/m2 D1-14 & TEM 75mg/m2D10-14, 8 wkly x 4; PRRT: 8 wkly x 4; CAPTEM 8 wkly x 4. Primary endpoint: Progression free survival (PFS). mNETS- at 15 months (mo) assuming 15mo PFS 66.4% in control arm, aiming for PFS ³ 80%; pNETS- at 12mo assuming 12mo PFS 60% in control arm, aiming for PFS ³ 75%. Secondary endpoints: Objective tumour response rate (complete or partial) (OTRR), clinical benefit rate (OTRR, stable disease) (CBR), toxicity, quality of life. Results: 75 pts enrolled (Dec 2015 – Nov 2018): mNETs 33 PRRT/CAPTEM and 14 PRRT; pNETS 19 PRRT/CAPTEM and 9 CAPTEM. mNETS: Median follow-up 35mo; 15mo PFS was 90% (95% CI: 73-97%) v 92% (95% CI: 57-99%); OTRR 31% vs 15%; and CBR 97% vs 92% for PRRT/CAPTEM v PRRT respectively. Treatment related adverse events (AEs): 24/32 PRRT/CAPTEM pts had at least one G3 event (75%) vs 5/13 (38%, PRRT); and 4/32 pts at least one G4 event (13%) v 1/13 (8%) respectively, mostly haematologic (haem). Only one patient failed to complete therapy (PRRT/CAPTEM). pNETS: Median follow-up 34mo; 12mo PFS was 76% (95% CI: 48-90%) v 67% (95% CI: 28-88%); OTRR 68% vs 33%; and CBR 100% vs 100% for PRRT/CAPTEM v CAPTEM respectively. Treatment related AEs: 5/18 PRRT/CAPTEM pts had at least one G3 event (28%) vs 3/9 (33%) CAPTEM; 3/18 pts at least one G4 event (17%) v 1/9 (11%) respectively. Conclusions: CAPTEM/PRRT is active, meeting its target landmark PFS for CAPTEM/PRRT (12mo pNETs; 15mo mNETs) with numerically greater OTRR in both pNETs and mNETs, but with more haem toxicity in mNETs. As activity was high in both control arms longer follow up is required to determine if the relative activity of PRRT/CAPTEM is sufficient to warrant Phase III evaluation. Clinical trial information: ACTRN12615000909527 .

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