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50mcg octreotide acetate by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge

Octreotide Acetate

Equivalent volume of 0.9% saline by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge

Saline Solution

Paracetamol 1g by mouth consumed with a 400kcal mixed meal challenge

Paracetamol

1g sulfasalazine by mouth consumed with a 400kcal mixed meal challenge

Biopsy from the second part of the duodenum taken at routine endoscopic surveillance, undertaken for another clinical indication.

Duodenal biopsy

John V Reynolds, MD FRCS

Carel W le Roux, FRCP FRCPath PhD

The incidence of oesophagogastric cancer has increased by 400% since the 1970s in Ireland and the United Kingdom. In addition, refinement of perioperative management and the now widespread use of multimodal protocols for patients with locally advanced disease have significantly improved outcomes for patients with oesophagogastric cancer treatable with curative intent. Despite significant advances in chemoradiotherapy, surgical resection remains the primary curative option.

Unintentional weight loss and nutritional complications represent serious concerns for patients after radical resection, even among those who remain free from recurrent disease in the long-term. A study from the Swedish Esophageal and Cardia Cancer Registry reported a mean three year weight loss of 10.8% among disease-free patients, with 33.8% of this cohort demonstrating malnutrition at three years post-oesophagectomy.

Mechanisms contributing to weight loss for disease-free patients after upper gastrointestinal surgery are poorly understood, however an association between increasing magnitude of weight loss and the presence of increased satiety is described. Our recent studies at SJH have demonstrated four fold elevated postprandial satiety gut hormone concentrations after oesophagectomy, compared with baseline preoperative values. Postprandial gut hormone levels correlate significantly with postprandial symptoms and altered appetite at 3 months postoperatively, and with body weight loss at 2 years postoperatively. However, the mechanism leading to exaggerated postprandial gut hormone production after upper gastrointestinal surgery is poorly understood, limiting targeted therapeutic options.

In this study, we aim to characterise the role of altered nutrient transit and enteroendocrine cell function in the pathophysiology of excessive post-prandial gut hormone responses after upper gastrointestinal surgery. To do this, we will measure the gut hormone response to a standardised 400 kcal meal, as per previous studies, while concurrently assessing gastrointestinal transit time, and enteroendocrine cell morphology and function. In this way, we will determine whether the magnitude of the postprandial gut hormone response correlates with the rate of nutrient transit into the enteroendocrine L-cell rich small intestine, and whether enteroendocrine cell adaptation occurs after oesophagectomy.

Furthermore, we have previously observed that gut hormone suppression using octreotide is associated with increased ad libitum among subjects after upper gastrointestinal cancer surgery (Elliott JA et al, Annals of Surgery, 2015). The mechanism of action of octreotide may relate to SSTR-5-mediated negative feedback to the enteroendocrine L-cell, but this medication may additionally reduce enteroendocrine L-cell responses through its inhibitory effect on gastrointestinal motility - reducing the rapidity with which nutrients are delivered to the small intestine - and small intestinal nutrient sensing via inhibition of the Na+-dependent glucose transporter SGLT-18-10. Through conduction of this double-blind, randomised, placebo-controlled crossover study, we aim to establish the mechanism of action of octreotide-mediated increased food intake in patients after gastrointestinal surgery. This may inform the design of future targeted interventions for this patient group.

Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery

St. James's Hospital, Ireland

Clinical Research Fellow

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Immune System Diseases

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Heart and Blood Diseases

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Diarrhea

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Purpura

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AL Amyloidosis

Gliclazide

Patients receive isatuximab IV on days 1, 8, 15, and 22 of course 1 and on days 1 and 15 of subsequent courses. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

Isatuximab

Laboratory Biomarker Analysis

Emma Scott

This phase II trial studies how well isatuximab works in treating patients with primary amyloidosis that has come back or does not respond to treatment. Monoclonal antibodies, such as isatuximab, may interfere with the ability of cancer cells to grow and spread.

PRIMARY OBJECTIVES:

I. To assess the efficacy as measured by the confirmed overall hematologic response rate (partial response or better) of isatuximab in relapsed/refractory systemic light chain (AL) amyloidosis.

SECONDARY OBJECTIVES:

I. To evaluate toxicities in the treatment of relapsed/refractory AL amyloidosis with isatuximab.

II. To evaluate time to hematologic response. III. To evaluate duration of response. IV. To evaluate progression-free survival (PFS). V. To evaluate overall survival (OS).

TERTIARY OBJECTIVES:

I. To evaluate efficacy of isatuximab in relapsed/refractory immunoglobulin amyloid light chain (AL) amyloidosis as measured by organ specific response rates (cardiac, renal, gastrointestinal \[GI\], liver, soft tissue, nerve), in the subset of patients that can be evaluated for organ response.

II. To evaluate time to organ response in the subset of patients that can be evaluated for organ response.

OUTLINE:

Patients receive isatuximab intravenously (IV) on days 1, 8, 15, and 22 of course 1 and on days 1 and 15 of subsequent courses. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days and then every at least every 6 months for up to 4 years.

S1702 Isatuximab in Treating Patients With Relapsed or Refractory Primary Amyloidosis

A Phase II Study of Isatuximab (SAR650984) (NSC-795145) for Patients With Previously Treated AL Amyloidosis

Will include partial response, very good partial response and complete response. Hematologic response will be reported with a binomial confidence interval.

Will be evaluated using the Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Organ response will be evaluated in the subset of patients with evaluable organ involvement using current criteria. The proportion of patients with organ response will be estimated as the number of patients with documented organ response out of the number of patients with documented evaluable organ involvement at baseline.

Will be estimated using the Kaplan-Meier method.

National Cancer Institute (NCI)

SWOG Cancer Research Network

Ear, Nose, and Throat Diseases

Weight Loss

Anorexia

Pain

Gastroesophageal Reflux

Body Weight

Vomiting

Deglutition Disorders

Mucositis

Exocrine Pancreatic Insufficiency

Malabsorption Syndromes

Flatulence

Steatorrhea

Bile Acids and Salts

The study will be limited to NHS patients to reduce complications associated with the need for additional funding authorisations from private health care providers for algorithm-instigated investigations. It is not envisaged that participation in other studies running within the GI unit at The Royal Marsden Hospital will preclude entry into this study except in the event of those rare studies where the study is specifically measuring toxicity of treatment as the primary end point.

Jervoise Andreyev, MBBS, Ph.D

Linda Wedlake, RD MSc BSc

The aim of the study is to identify how often gastrointestinal problems interfere with quality of life as a result of treatment for cancer with chemotherapy. We also want to identify the causes for these symptoms and see if simple treatments used for other gastrointestinal conditions could make chemotherapy an easier experience. Chemotherapy for cancer can be hard work for the patient. Often it makes them feel tired. Not infrequently, it can cause a whole range of physical side effects. Probably the most common side effects are those affecting the stomach and bowels. Vomiting used to be a major problem with chemotherapy but research discovered a whole series of new treatments so that severe vomiting from chemotherapy is rarely a problem today. However, patients can develop a whole series of other symptoms during chemotherapy, for example, bloating, wind, diarrhoea, needing to rush to the lavatory and opening the bowels very frequently. The causes for these symptoms have hardly been studied even though they sometimes affect people quite badly. In our specialist gastrointestinal clinic at the Royal Marsden Hospital, over the last 12 years, we have pioneered new methods for dealing with symptoms which affect the bowel after radiotherapy. We would like to extend these methods to people having chemotherapy. We have identified several easily treatable causes for these symptoms after radiotherapy, which previously were often ignored. We believe that some of these causes also occur in people having chemotherapy and if we knew how often they do occur we could focus on improving treatment for affected people. We plan to find out how often 40 stomach and bowel symptoms occur during chemotherapy. In people who are troubled by any or some of these symptoms we will arrange simple series tests which could sort out why these symptoms occur and we will record how they respond to treatment.

Chemotherapy (CT) remains an integral part of treatment for many types of cancer often in combination with surgery and/or radiotherapy. In the year March 2011 to April 2012, 1807 patients were referred to the Royal Marsden Hospital (RMH) Gastrointestinal Unit with a new gastro intestinal (GI) cancer of whom 709 were treated with chemotherapy alone or in combination with other long term outcome. GI symptoms are common in patients receiving chemotherapy. They may arise from the tumour, but may also result as a side effect of treatment. They include anorexia, borborygmi, bloating, constipation, diarrhoea, dysphagia, early satiety, frequency of defaecation, incontinence, mucus discharge, nausea, nocturnal defaecation, pain, reflux, regurgitation, steatorrhoea, tenesmus, urgency of defaecation, vomiting, weight loss and wind. Frequently, such symptoms have a significant impact on patients' quality of life. They may also interfere with the delivery of treatment prompting cessation of therapy or dose reduction resulting in sub optimal dosage with a potential impact on morbidity and mortality. Whilst clinicians have long focused on the management of vomiting and pain in cancer patients, less attention has been paid to the incidence, severity or optimal management of other GI symptoms. If the cause of these symptoms can be identified, then appropriate investigations and treatments can be prescribed. The GI Unit has successfully investigated and treated patients with symptoms emerging after radiotherapy. This experience has enabled the team to develop an algorithm for facilitating the investigation and treatment of cancer therapy induced symptoms. The algorithm has recently been shown to be effective in the management of patients with radiation induced bowel injury . In particular, it enables the rapid identification of required investigations and improves the management of symptoms that might otherwise be mislabeled as inevitable consequences of treatment. Five easily treatable causes for GI symptoms have so far been identified:

* Small bowel bacterial overgrowth
* Carbohydrate malabsorption
* Bile acid malabsorption
* Gastric bile reflux
* Pancreatic insufficiency

It is likely that additional causes such as viral infections (eg cytomegalovirus) are more frequent in patients undergoing chemotherapy than currently appreciated.

Blood and Stool Samples will be collected for translational analysis.

The FOCCUS Study: "Focusing on Cancers Chemotherapys' Untreated Symptoms"

The FOCCUS Study: "Focusing on Cancer Chemotherapys' Untreated Symptoms"

Royal Marsden NHS Foundation Trust

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery	NCT03734627	Esophageal Canc... Nutrition Disor... Appetite Disord... Dumping Syndrom... Delayed Gastric... Surgery	Octreotide Acet... Saline Solution Paracetamol Sulfasalazine Duodenal biopsy	18 Years -	St. James's Hospital, Ireland
S1702 Isatuximab in Treating Patients With Relapsed or Refractory Primary Amyloidosis	NCT03499808	Amorphous, Eosi... Constipation Diarrhea Early Satiety Gastrointestina... Hepatomegaly Lymphadenopathy Macroglossia Nausea Primary Systemi... Purpura Recurrent Prima... Refractory Prim...	Isatuximab Laboratory Biom...	18 Years -	SWOG Cancer Research Network
The FOCCUS Study: "Focusing on Cancers Chemotherapys' Untreated Symptoms"	NCT02121626	Cancer		18 Years - 90 Years	Royal Marsden NHS Foundation Trust

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