Promelaxin Microenemas Are Non-inferior to Oral Polyethylene Glycol for the Treatment of Functional Constipation in Young Children: A Randomized Clinical Trial

Background: Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC.Aim: To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC.Methods: This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6–48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with “response” defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints.Results: Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55–31.49%) and 11.03% (CI −5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; p = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm (p < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin (p = 0.036).Conclusions: Promelaxin microenemas are non-inferior to oral PEG in children with FC.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02751411.

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Dual immune checkpoint blockade in advanced well-differentiated neuroendocrine tumors, a phase II clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16201 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16201-e16201

Author(s):

Susan Combs Scott ◽

Ana De Jesus-Acosta ◽

Chen Hu ◽

Benjamin Philip Levy ◽

Valsamo Anagnostou ◽

...

Keyword(s):

Clinical Trial ◽

Neuroendocrine Tumors ◽

Phase Ii ◽

Median Duration ◽

Primary Endpoint ◽

Response Rate ◽

Objective Response ◽

Phase Ii Clinical Trial ◽

Open Label ◽

Well Differentiated

e16201 Background: Limited systemic treatment options are available for progressive well-differentiated neuroendocrine tumors (NET), also called carcinoid tumors. Given emerging evidence for immunotherapy response in high grade NET including small cell lung cancer, we sought to determine the efficacy of combination immunotherapy with ipilimumab and nivolumab in patients with advanced, progressive, well-differentiated NET in an open label phase II clinical trial. Methods: Eligible patients had well-differentiated, nonfunctional NET of lung, pancreas, or GI origin that had progressed within the past 12 months after at least one line of prior therapy. Patients received nivolumab 240 mg every 2 weeks and ipilimumab 1mg/kg every 6 weeks for up to 2 years. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Using a Simon’s 2-stage design, the study planned to accrue up to 56 patients. Based on published response rates to everolimus of 5%, we hypothesized that this regimen would be considered promising if the true ORR is > 15%. Results: Nine patients were enrolled prior to study closure due to funding, including 6 patients with NET of lung origin, 2 pancreatic, and 1 small bowel (Table). Median age was 71 years. All patients had distant metastatic disease at enrollment, with an average of 2 prior lines of therapy. Four of 9 patients achieved the primary endpoint of confirmed objective response, all of whom have ongoing response with a median duration of 15.4 months. Five of 9 patients, including all 4 responders, experienced immune-related toxicity requiring treatment modification or discontinuation. The trial did not accrue the target of 56 patients, however, objective response in 4 of 9 patients (ORR 44.4%, 90% CI: 16.9-74.9%) excluded the response rate target (15%). Conclusions: The impressive ORR of 44% with a median duration of response exceeding 15 months in this small clinical trial warrants further study of combination CTLA-4 and PD-1 inhibition in previously treated well-differentiated NET. Our ongoing immunologic and genomic correlative analysis in responders and non-responders will help inform future study of immunotherapy in this patient population in need of new systemic therapy approaches. Clinical trial information: NCT03420521. [Table: see text]

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Comparison of the effect of polyethylene glycol and simultaneous administration of polyethylene glycol with probiotics in the treatment of chronic functional constipation: a clinical trial

Journal of Shahrekord University of Medical Sciences ◽

10.34172/jsums.2020.21 ◽

2020 ◽

Vol 22 (3) ◽

pp. 135-140

Author(s):

Karamali Kasiri ◽

Morteza Sedehi ◽

Sheida Mortazavi

Keyword(s):

Clinical Trial ◽

Body Weight ◽

Polyethylene Glycol ◽

Lactobacillus Rhamnosus ◽

Functional Constipation ◽

Water Soluble ◽

Fecal Excretion ◽

Simultaneous Administration ◽

Double Blind ◽

Significant Difference

Background and aims: Constipation is one of the most common issues in pediatrics. The aim of this study was to compare the effect of polyethylene glycol and the simultaneous administration of polyethylene glycol along with probiotics in the treatment of chronic functional constipation. Materials and Methods: In this randomized double-blind clinical trial, 150 children with chronic functional constipation referred to Imam Ali Clinic affiliated with Shahrekord University of Medical Sciences from 2017 to 2018 were included. The first group (A) consumed 1 g/ kg of body weight per day of water-soluble polyethylene glycol powder and the second group (B) consumed a probiotic powder and 1 g/kg of body weight of the water-soluble polyethylene glycol powder daily. In weeks 0, 1, and 2, questionnaires were filled out by the parents of the children and the data were analyzed. Results: The results showed that there was no significant difference in any of the variables between groups A and B (P=0.07) including the frequency of fecal excretion in week 1 (77% and 71%) and week 2 (4% and 5.4%) and stool consistency in week 1 (4% and 6.7%) and week 2 (86.7% and 92%). Moreover, there was no significant difference between groups A and B in any of the variables frequency of painful excretion in week 1 (74% and 73%, respectively) and week 2 (5.3% and 4%, respectively), frequency of abdominal pain in week 1 (61.3% and 49.3%, respectively) and week 2 (4% and 5.3%, respectively), and the frequency of fecal incontinence in week 1 (22.77% and 18.7%, respectively) and week 2 (6.7% and 1.3%) (P>0.05, respectively). Conclusion: Our results indicated that the administration of probiotic supplement (Lactobacillus Rhamnosus, Lactobacillus acidophilus, Lactobacillous Bulgaricus) has no effect on the improvement of symptoms in children with chronic constipation.

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The randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3501 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3501-3501

Author(s):

Akihito Tsuji ◽

Hisatsugu Ohori ◽

Tatsuro Yamaguchi ◽

Masato Matsuura ◽

Atsujiro Nishioka ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Primary Endpoint ◽

Line Treatment ◽

Wild Type ◽

First Line ◽

Randomized Phase Ii ◽

Secondary Endpoints ◽

Clinical Trial Information ◽

First Line Treatment

3501 Background: Triplet regimens, FOLFOXIRI, combined with bevacizumab (bev) or panitumumab have been shown to be superior in terms of early tumor shrinkage (ETS) and depth of response (DpR) compared to doublet combinations in patients with RAS wild-type metastatic colorectal cancer (mCRC), in the TRIBE trial ( N Engl J Med 2014) or the VOLFI trial ( J Clin Oncol 2019), respectively. There have been few studies which directly compared cetuximab (cet) with bev when combined with triplet regimen. Therefore, we investigated the efficacy and safety of bev vs. cet in combination with FOLFOXIRI in previously untreated mCRC patients with RAS wild-type tumors. Methods: This trial was a randomized phase II trial to evaluate modified (m)-FOLFOXIRI (irinotecan 150mg/m2, oxaliplatin 85mg/m2, 5-FU 2400mg/m2) plus cet vs. bev as first-line treatment in terms of DpR during the entire course as the primary endpoint in 360 patients with RAS wild-type mCRC. The aim of the trial was to show that median DpR of cet arm was more than 12.5% higher than bev arm, with a power of 85% at a significance level of 0.05. Secondary endpoints included ETS rate at week 8, overall response rate (ORR), progression-free survival (PFS), overall survival (OS), secondary resection rate, and toxicity. Results: A total of 359 patients were enrolled between July 2015 and June 2019. For the full analysis set (median age 65y, 64% male, PS0/1: 91%/9%, left/right primary: 83%/17%), 173 and 175 patients were randomly assigned to the cet and bev arms, respectively. On the cutoff date of September 2020, the median number of cycles administered was 10 (range, 1-51) for the cet arm and 12 (range, 1-51) for the bev arm. Safety data was already reported at the ASCO GI symposium 2021 (J Clin Oncol 39, 2021 suppl 3; abstr 86). The primary endpoint was met (p =.001); 57.4%（-15.0̃100）for the cet arm versus 46.0% （-0.6̃100）for the bev arm. As for primary tumor sidedness, median DpR were 60.3% versus 46.1% (p =.0007) in the left-side and 50.0% versus 41.2% (p =.46) in the right-side. The ETS rate and ORR as the secondary endpoints were 77.8% and 69.1% in the cet arm versus 74.6% and 71.7% in the bev arm, respectively, with no statistical significance. Although the survival data were immature, PFS and OS of both arms were 12.7 months (95%CI 11.5-14.0) and 37.6 months (95%CI 30.8 to 43.0), respectively. Conclusion: The mFOLFOXIRI plus cet has been shown to be significantly superior to the mFOLFOXIRI plus bev in terms of DpR as the primary endpoint in first-line treatment for RAS wild-type mCRC. Clinical trial information: NCT02515734. Clinical trial information: UMIN000018217.

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Single Dose or Divided Dose of Polyethylene Glycol in Treatment of Pediatric Functional Constipation: A Randomized Clinical Trial

10.21203/rs.3.rs-977795/v1 ◽

2021 ◽

Author(s):

Heidar Safarpour ◽

Mohammad Hadi Imanieh ◽

naser honar ◽

sajad hekmati ◽

Naeimehossadat Asmarian

Keyword(s):

Clinical Trial ◽

Single Dose ◽

Polyethylene Glycol ◽

Randomized Clinical Trial ◽

Divided Dose ◽

Functional Constipation ◽

Significant Difference ◽

Group A ◽

The Mean ◽

Group B

Abstract BackgroundThis study aimed to compare different regimens of Polyethylene Glycol (PEG, single dose vs. divided dose) in the treatment of functional constipation among children aged 4-15 years.Materials and MethodsThis double-blind randomized clinical trial was conducted on the children (4-15 years old) with functional constipation who were visited in an outpatient pediatric clinic affiliated to Shiraz University of Medical Sciences between February and July 2021. Among the120 eligible patients, 80 ones who met the inclusion criteria were recruited. The patients were divided into two parallel groups; the children who received single-dose PEG (group A) and those who received PEG in divided doses (group B). The study was performed during 12 weeks and follow-up visits were scheduled at 1, 3, 6, and 12 weeks after enrollment. The outcomes were measured using the Bristol Stool Form Scale (BSFS).ResultsThe study was performed on 78 cases including 45 boys (57.7%) and 33 girls (42.3%) with the mean age of 5.52±1.79 years. After 12 weeks, a significant difference was observed between groups A and B regarding the mean of BSFS (4.94±0.52 vs. 4.50±0.88, p=0.008). However, no significant difference was observed between the two groups regarding the number of defecation times during the study. The detected complications included mild abdominal pain in eight children in group A (5.3%), fecal incontinency in six children in group B (3.8%), and painful defecation in six children in group B (3.8%).ConclusionThis study confirmed that the administration of the single dose (0.4 g/kg) of PEG early in the morning was more effective, well tolerated, and accompanied by fewer complications compared to the divided dose.

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First-in-human phase I/II trial of PRGN-2009 vaccine as monotherapy or with bintrafusp alfa in patients with recurrent/metastatic (R/M) human papillomavirus (HPV)-associated cancers (HPVC) and as neoadjuvant/induction therapy in locoregionally advanced (LA) HPV oropharyngeal (OP) and sinonasal (SN) squamous cell cancer (SCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps6092 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS6092-TPS6092

Author(s):

Charalampos S. Floudas ◽

Julius Strauss ◽

Clint Allen ◽

Nyall R London ◽

Renee Nicole Donahue ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Phase Ii ◽

Induction Therapy ◽

Primary Endpoint ◽

Post Treatment ◽

Stage Ii ◽

Newly Diagnosed ◽

Secondary Endpoints ◽

Previously Treated

TPS6092 Background: R/M HPVC (cervical, anal, oropharyngeal, etc.) are incurable by current therapies. For newly diagnosed LA HPV-OPSCC standard-of-care (SOC) is radiotherapy ± chemotherapy (C/RT) or surgery ± adjuvant C/RT, with considerable risk of relapse. Newly diagnosed LA SNSCC treatment follows the OPSCC paradigm, and detection of HPV appears to confer improved prognosis. Neoadjuvant PD-1 immune checkpoint blockade (ICB) before surgery may improve RFS and is being evaluated in a multicenter phase III clinical trial (Keynote-689). PRGN-2009 (P) is a novel gorilla adenovirus vaccine containing 35 non-HLA-restricted epitopes of HPV 16 and 18 shown to induce HPV specific responses (preclinical models). Bintrafusp alfa (BA) is a bifunctional fusion protein targeting TGF-β and PD-L1 with promising activity in HPVC. This trial will evaluate the safety and activity of P/ P + BA in patients with previously treated R/M HPVC and as neoadjuvant/induction therapy before SOC surgery or C/RT in newly diagnosed LA HPV-OPSCC and HPV-SNSCC. Methods: This is a first-in-human, investigator-initiated, single-center phase I/II trial. Pts with previously treated (incl. ICB) R/M HPVC are eligible for Phase I: P dose escalation arm (3+3 design, 6-12 patients) testing 2 dose levels (1x1011, 5x1011 viral particle units, SC Q2W three times, then Q4W), and combination arm (10 patients) testing P (recommended phase 2 dose (RP2D), same schedule) + BA (1200 mg IV Q2W). Treatment (both arms) will continue until disease progression, unacceptable toxicity, decision to withdraw. Primary endpoint is safety. Secondary endpoints include ORR (RECIST 1.1), PFS, and OS. For Phase II, patients with newly diagnosed stage II/III (AJCC Cancer Staging Manual, 8th ed.) HPV-OPSCC and stage II/III/IVA/IVB HPV-SNSCC planned for SOC C/RT or surgery will be eligible for two treatment arms of 20+2 patients each (sequential): P arm and P + BA, to evaluate the treatment activity. All patients will have pre-treatment biopsy, receive two cycles of the study treatment at the NCI Clinical Center two weeks apart, followed by post-treatment biopsy and SOC treatment (at the referring institution) 4 weeks after the first study treatment. Primary endpoint is post-treatment ≥2-fold increase in tumor-infiltrating CD3+ cells. Secondary endpoints include RFS, OS. Exploratory endpoints for both arms include analyses of immune subsets, soluble factors, and HPV-specific immune responses in peripheral blood and tissue where available, and in Phase II sequencing (exome, scRNA), immune spatial profiling with multiplex immunofluorescence, and salivary HPV DNA. Clinical trial registry: NCT04432597. Clinical trial information: NCT04432597.

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Functional constipation in young children: causes, diagnostic criteria and therapeutic strategies

Medical Council ◽

10.21518/2079-701x-2018-17-150-155 ◽

2018 ◽

pp. 150-155

Author(s):

N. M. Bogdanova

Keyword(s):

Polyethylene Glycol ◽

Young Children ◽

Diagnostic Criteria ◽

Mechanism Of Action ◽

Functional Constipation ◽

Therapeutic Strategies ◽

Main Mechanism ◽

Definition Of ◽

Qualitative Characteristics

The article gives a modern definition of constipation and working classification used in Pediatrics; frequency of defecation and qualitative characteristics of stool depending on age and type of feeding are presented. Particular attention is paid to the reasons for the development of functional constipation in young children, diagnostic criteria in accordance with the Rome consensus IV revision (2016) and tactics of management of children with constipation. Part of the information is devoted to the use of osmotic laxatives. The main mechanism of action of polyethylene glycol and its advantages in stopping constipation in infants older than 6 months are shown. age’s.

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Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.10004 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 10004-10004 ◽

Cited By ~ 4

Author(s):

Daniel Olson ◽

Jason J. Luke ◽

Andrew Stewart Poklepovic ◽

Madhuri Bajaj ◽

Emily Higgs ◽

...

Keyword(s):

Clinical Trial ◽

Antitumor Activity ◽

Primary Endpoint ◽

Response Rate ◽

Progression Free Survival ◽

Open Label ◽

Free Survival ◽

Prior Therapy ◽

Length Of Treatment ◽

Grade 3

10004 Background: Combination PD1 + CTLA4 antibodies (Abs) shows greater response rate (RR) versus PD1 Ab alone in MEL, but RR after initial PD1 Ab progression awaits robust investigation. CTLA4 Ab alone after PD1 Ab progression has a historical RR of 13%. We report final results of the first prospective clinical trial evaluating IPI 1mg/kg + PEMBRO immediately following progression on PD1 Ab (NCT02743819). Methods: Patients (pts) with advanced MEL, no prior CTLA4 Ab for metastatic disease, and who had progressed on PD1 Ab as immediately prior therapy (or non-CTLA4 Ab combination) were eligible. Pts received PEMBRO 200 mg + IPI 1 mg/kg Q3W for 4 doses, then PEMBRO alone for up to two years. The primary endpoint was RR by irRECIST. After 35 pts, the study met its primary endpoint with 10/22 evaluable pts achieving a response. The trial was expanded to enroll a total of 70 pts in open-label accrual to further describe the RR for this regimen in an exploratory fashion. The data analysis cutoff was January 30, 2020. Results: 67/70 accrued patients were evaluable for treatment response. Prior treatments included 60 on PD1 Ab alone and 10 on PD1 Ab-based combinations. Of these, 10 pts had progressed in the adjuvant setting. Median length of treatment on prior PD1 Ab was 4.8 months. Response assessments included 4 CR, 17 PR and 16 SD for a RR of 31% (21/67) in evaluable pts, and 30% (21/70) in all enrolled pts. 4 pts with a PR and 6 with SD had unconfirmed responses making the irRECIST response rate 25% (17/67) and 24% (17/70) among evaluable and enrolled pts, respectively. Median progression free survival (PFS) was 4.7 mo (95% CI: 2.8-8.3) and PFS at six months was 45% (95% CI: 33%-57%). 15/70 (21%) pts experienced ≥ grade 3-4 drug-related AEs, the most common being diarrhea, rash and transaminase elevation. PD-L1 positive vs negative status from historical tumor specimens did not associate with RR. Conclusions: This is the largest prospective study of IPI 1mg/kg + PEMBRO, demonstrating significant antitumor activity and tolerability in MEL post-PD1 Ab. Clinical trial information: NCT02743819.

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Impact of renal impairment on clinical outcomes in patients (pts) with locally advanced or metastatic (LA/M) urinary tract carcinoma (UTC) treated with atezolizumab (atezo): Analysis of the international SAUL study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5036 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5036-5036

Author(s):

Margitta Retz ◽

Florian Seseke ◽

Giuseppe Luigi Banna ◽

Ugo De Giorgi ◽

Thomas Powles ◽

...

Keyword(s):

Clinical Trial ◽

Renal Impairment ◽

Overall Response Rate ◽

Response Rate ◽

Locally Advanced ◽

Exclusion Criteria ◽

Secondary Endpoints ◽

Post Hoc ◽

Unacceptable Toxicity ◽

Clinical Trial Information

5036 Background: Atezo, which targets PD-L1, is an approved therapy for LA/M urothelial carcinoma based on the IMvigor210 and IMvigor211 trials. The single-arm SAUL study (NCT02928406) showed consistent activity and safety in a broader population, including understudied scenarios, eg pts with renal impairment or other IMvigor211 exclusion criteria. Methods: Pts with LA/M UTC received atezo 1200 mg q3w until disease progression or unacceptable toxicity. The primary endpoint was safety; secondary endpoints included overall response rate (ORR) and overall survival (OS). Post hoc analyses explored outcomes in pts classified as: chemotherapy (CT) ineligible (calculated creatine clearance [CrCl] 15– < 30 mL/min); cisplatin ineligible and carboplatin eligible (CrCl 30– < 60 mL/min); or cisplatin eligible (CrCl ≥60 mL/min). Results: Of 1004 enrolled pts, 46 (5%) were classified as CT ineligible and 420 (42%) as cisplatin ineligible. Results are summarized below. Conclusions: These post hoc analyses suggest pts typically considered cisplatin or CT ineligible are candidates for atezo. Pts with renal impairment achieved similar ORR and DCR to pts with CrCl ≥60 mL/min, without increased toxicity. Imbalances in pt characteristics may explain numerical differences in OS. Clinical trial information: NCT02928406 . [Table: see text]

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