Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Adenocarcinoma

Pain

Abdominal Pain

Celiac Disease

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Central Nervous System Depressants

All Drugs and Chemicals

Anti-Infective Agents

Bupivacaine

Ethanol

CPN will be undertaken at the celiac space which is located between the aorta and the celiac artery origin. A 22 or 19-gauge Fine Needle Aspiration (FNA) needle is used, and its tip is placed slightly anterior and cephalic to the origin of the celiac artery. Aspiration is first performed using a syringe to ensure that vascular puncture has not occurred. 10 mL Bupivacaine is injected first, followed by 20 mL of 98% alcohol.

Once the celiac ganglia are identified on EUS, a 19-gauge FNA needle is inserted into the center of the ganglion or area of celiac plexus under EUS guidance. The radiofrequency (RF) probe (EMcision, Montreal, Canada) is advanced through the FNA needle. Radiofrequency ablation is performed via the probe for 90 seconds, followed by a 90 second rest and repeated as required.

This intervention involves accessing the Celiac Plexus Nerve via endoscopic guided ultrasound and then injecting the nerve bundle with bupivacaine.

Celiac Plexus Neurolysis

Radiofrequency ablation is performed via the probe for 90 seconds, followed by a 90 second rest. This is repeated until the entire ganglion becomes hyperechoic on EUS.

Radiofrequency Ablation

Shyam S Varadarajulu, MD

Pancreatic cancer is the second most common gastrointestinal malignancy. Abdominal discomfort is a main symptom in patients with pancreatic cancer. Approximately 75% have pain at diagnosis and over 90% in advanced stages. Pain control is an important part of the plan of care for patients with pancreatic cancer.. The celiac plexus is a group of nerves that supply organs in the abdomen. EUS-guided celiac plexus neurolysis (EUS-CPN) has been widely used for pain management in patients with pancreatic cancer. Radiofrequency ablation of celiac ganglia or celiac plexus (EUS-RFA) is also being performed to alleviate abdominal pain in pancreatic cancer patients. However currently no comparative studies exist comparing EUS-CPN with EUS-RFA. The purpose of the study is to compare EUS-CPN with EUS-RFA for pain management in pancreatic patients, in order to determine which technique is better at improving pain in pancreatic cancer patients.

Pancreatic cancer is the second most common gastrointestinal malignancy and fourth leading cause of cancer mortality. The incidence in the US is estimated at 8.8 per 100,000 population with 30,000 new cases diagnosed annually. The prognosis of unresectable pancreatic cancer is poor; overall 1 and 5-year survivals do not exceed 20 and 4%, respectively. For the minority of patients (15%) who are resectable at diagnosis, the median survival is 10-20 months, with 5-year survival of 10-25%.

Abdominal discomfort is a predominant symptom in patients with pancreatic cancer. Approximately 75% have pain at diagnosis and over 90% in advanced stages. Therefore a major aspect of palliation is provision of adequate pain control. The standard approach to pain management is based on the World Health Organization (WHO) 3-step ladder, beginning with non-opioid analgesics (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen), followed by weak opioids and then finally strong opioids as necessary. Virtually all patients require escalating doses of opioids during their disease. Adjuvant therapies, including other medications (e.g. trazodone, tricyclic anti-depressants, and bisphosphonates), palliative radionucleotides, external beam radiation, or chemotherapy may also be useful for symptomatic control.

In the last 10 years, EUS-guided celiac plexus neurolysis (EUS-CPN) has been widely practiced for alleviation of pain in patients with pancreatic cancer and has been shown to be effective. At our institution, radiofrequency ablation (EUS-RFA), which involves ablation of celiac ganglia or celiac plexus using a radiofrequency catheter, is being performed to alleviate abdominal pain in pancreatic cancer patients. However currently no comparative studies exist comparing EUS-CPN with EUS-RFA for pain alleviation in pancreatic cancer patients.

In this randomized trial, the investigators will be comparing EUS-CPN with EUS-RFA for pain alleviation in pancreatic patients, in order to determine which technique is better at improving pain in pancreatic cancer patients.

Subjects will randomized to either a group that receives Celiac Plexus Neurolysis or Radiofrequency Ablation.

Trial Comparing EUS-guided Radiofrequency Ablation vs. EUS-guided Celiac Plexus Neurolysis

Randomized Trial Comparing Endoscopic Ultrasound-guided Radiofrequency Ablation vs.Endoscopic Ultrasound-guided Celiac Plexus Neurolysis in the Alleviation of Abdominal Pain in Patients With Pancreatic Cancer

There is no plan to share individual participant data (IPD).

Abdominal pain will be assessed with pain scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer module (QLQ-PAN26). The questionnaire has 26 questions with scoring ranging from a minimum of 26 to a maximum of 104. The higher the score, the worse the subject's quality of life rating.

Quality of life (QOL) as assessed by the quality of life instrument: the Functional Assessment of Cancer Therapy, Pancreatic Cancer (FACT-PA) (i.e. QLQ-30 and PAN-26)

Subjects will be asked about their medication usage to manage pain and the answers will be documented.

Cross-over to the alternate technique due to inadequate response to the original technique (defined as \< 50% decrease in VAS score post-original technique).

Information regarding complications if any, that the subject may have experienced, which can include hypotension, diarrhea, neuropathic pain, paraplegia and endoscopic adverse events

Information regarding if the subject is alive or deceased.

Abdominal pain will be assessed with a standardized 11-point continous visual analog pain scale (with "0" equaling no pain, "5" moderate pain and "10" worst pain ever.

AdventHealth

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Agents

Pancrelipase

Pancreatin

Participants with stage 4 Pancreatic Ductal Adenocarcinoma / PDAC will receive 384 units lipase/kg of body weight per meal or snack

Participants with stage 4 Pancreatic Ductal Adenocarcinoma / PDAC will receive 1350 units lipase/kg of body weight per meal or snack

Treatment with standard dose or higher dose Pancrelipase will continue for 20 weeks from enrollment. Participants will consume assigned blinded weight based Pancrelipase dose concurrent with first bite of every meal and snack for the duration of enrollment.

Pertzye

Eileen O'Reilly, MD

Mark Schattner, MD

The main purpose of this study is to see how pancrelipase affects the body mass index (BMI) in people with metastatic PDAC. BMI is a measure based on a person's height and weight. Other study goals are to explore two different dosing schedules of pancrelipase and to evaluate pancrelipase in people who do not have symptoms of EPI.

Pancrelipase in People With Pancreatic Ductal Adenocarcinoma (PDAC)

A Randomized Double Blind Study of Pancreatic Enzyme Replacement Therapy for Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary objective is a change in body mass index (BMI) 4 months from baseline while on pancreatic enzyme replacement therapy (PERT).

Memorial Sloan Kettering Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Antineoplastic Agents

Pharmaceutical Solutions

Gemcitabine

Maytansine

Antimetabolites

Tubulin Modulators

Antimitotic Agents

tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)

tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)

Pharmaceutical form:Concentrated solution for IV;

Route of administration: IV infusion

tusamitamab ravtansine

Pharmaceutical form: Lyophilized powder for reconstitution or as a solution for infusion;

Route of administration: IV infusion

Clinical Sciences & Operations

Primary Objective:

* For Cohort A, Cohort B, and Cohort C Part 2: To assess the antitumor activity of tusamitamab ravtansine in metastatic breast cancer (mBC) and tusamitamab ravtansine monotherapy and in combination with gemcitabine in metastatic pancreatic adenocarcinoma (mPAC)
* For Cohort C Part 1: Confirmation of the recommended tusamitamab ravtansine dose when administered in combination with gemcitabine

Secondary Objectives:

* To assess the safety and tolerability of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
* To assess other efficacy parameters of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
* To assess the immunogenicity of tusamitamab ravtansine
* To assess the pharmacokinetics (PK) of tusamitamab ravtansine and gemcitabine when given in combination

The expected duration of study intervention for participants may vary, based on progression date and the cohort; median expected duration of study per participant is estimated at 8 months for Cohort A/C and 6 months for Cohort B (up to 1 month for screening, a median of 4 or 2 months for treatment in Cohort A/C and Cohort B respectively, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).

Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

Open-label, Multi-cohort, Phase 2 Trial, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine (SAR408701) Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Objective Response Rate (ORR) of tusamitamab ravtansine in mBC and tusamitamab ravtansine monotherapy and in combination with gemcitabine in mPAC, defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.

Incidence of dose-limiting toxicites (DLTs) in the 28 Day DLT observation period (Cycle 1)

TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE v5.0.

PFS defined as the time from the date of first tusamitamab ravtansine administration to the date of the first documented disease progression or death due to any cause, whichever comes first.

DCR defined as the percentage of participants who have achieved CR, PR or stable disease as per RECIST v1.1.

DOR defined as the time from first documented evidence of CR or PR until progressive disease determined per RECIST v1.1 or death from any cause, whichever occurs first.

Incidence of participants with anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine.

Pharmacokinetic parameter of tusamitamab ravtansine.

Pharmacokinetic parameter of tusamitamab ravtansine. AUC0-14d calculated using the trapezoidal method.

Pharmacokinetic parameter of gemcitabine.

Pharmacokinetic parameter of gemcitabine metabolite.

Sanofi

Lenalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Phase I; Lenalidomide capsules will be taken orally each day on days 1-21 of each 28-day cycle. 3 subjects will be enrolled into each dose cohort for 15, 20 and 25 mg/day. Gemcitabine, 1000 mg/m2 in 0.9% sodium chloride will be administered iv over 30 minutes, at days 1, 8, 15 of each 28-day cycle. Phase II: Every other consecutive included subject in phase II part will be treated with either single lenalidomide (days 1-21 of 28) or single gemcitabine (days 1, 8, 15 of 28) during Cycle 1. The first included patient in phase II part will start with single lenalidomide. From treatment cycle number 2 and beyond, all subjects in the phase II part of the study will be treated with lenalidomide in combination with gemcitabine.

Gemcitabine, 1000 mg/m2 in 0.9% sodium chloride will be administered iv over 30 minutes, at days 1, 8, 15 of each 28-day cycle in both phase I and II. Phase I:Lenalidomide capsules will be taken orally each day on days 1-21 of each 28-day cycle. 3 subjects will be enrolled into each dose cohort for 15, 20 and 25 mg/day. Phase II: Every other consecutive included subject in phase II part will be treated with either single lenalidomide (days 1-21 of 28) or single gemcitabine (days 1, 8, 15 of 28) during Cycle 1. The first included patient in phase II part will start with single lenalidomide. From treatment cycle number 2 and beyond, all subjects in the phase II part of the study will be treated with lenalidomide in combination with gemcitabine.

Gemcitabine (Gemzar®), 1000 mg/m2 in 0.9% sodium chloride will be administered as intravenous infusion over 30 minutes, weekly for 3 weeks then rest for 1 week (days 1, 8, 15 of each 28-day cycle).

Gemzar

Lenalidomide capsules will be taken orally in the morning each day on days 1-21 of each 28-day cycle. Phase I; Three subjects will be enrolled into each dose cohort for 15, 20 and 25 mg/day, respectively. Phase II; Lenalidomide at dose determined in Phase I, will be administered orally once daily for 21 days followed by 7 days rest.

Revlimid

Håkan Mellstedt, Prof.

The purpose of this study is to ascertain whether treatment with lenalidomide or lenalidomide in combination with gemcitabine induces modulation of immune effector functions and to characterize the nature of immune functions.

Pancreatic cancer is characterised by aggressive growth, treatment resistance and an extremely poor prognosis. In subjects with locally advanced or metastatic disease, the median survival is approximately 6 - 11 months and 2 - 6 months, respectively. The currently accepted treatment for this disease in EU is gemcitabine which supplanted treatment with 5-FU after it was shown that median survival duration was marginally improved (4.41 and 5.65 months respectively, p = 0,022). The reported median survival time for subjects treated with single-agent gemcitabine in randomized phase III studies ranged form 4.9 to 7.2 months. Despite these improvements in the treatment of pancreatic cancer, the prognosis remains very poor. Lenalidomide (Revlimid®) belongs to a proprietary class of compounds called immunomodulatory drugs (IMiDs). IMiDshave both immunomodulatory and anti-angiogenic properties which could confer antitumour and antimetastatic effects. Lenalidomide has been demonstrated to possess anti-angiogenic activity through inhibition of bFGF, VEGF and TNF-alpha induced endothelial cell migration, due at least in part to inhibition of Akt phosphorylation response to bFGF.In addition, lenalidomide has a variety of immunomodulatory effects. Gemcitabine (Gemzar®) is a synthetic pyrimidine nucleoside analogue that is used as standard treatment of advanced pancreatic cancer. Beside the cytotoxic activity of gemcitabine, accumulating evidence has indicated that the product promote specific anticancer immune responses that contribute to the therapeutic effects of conventional therapy.Down-regulation in survival rate of pancreatic cell lines has more recently been observed, when treated with lenalidomide and gemcitabine in sub-optimal concentrations.Those data supports a hypothesis of a potential hyper-additive affect of the treatments given in combination. Therefore lenalidomide and gemcitabine should be of major interest to explore for combination therapy.

This is a phase I/II open-label, multi-center study. It will consist of a phase I dose-finding part and a phase II part during which subjects will be treated at the MTD established during phase I. Lenalidomide will be administered by a stepwise dose-escalation schedule in the phase I part. Thus, the primary endpoint in the phase I part is to determine the MTD and safety of the regimen lenalidomide and gemcitabine as first-line treatment in subjects with advanced pancreatic cancer.In the phase II part, primary endpoint is to evaluate the immunomodulatory effects of lenalidomide in combination with gemcitabine in the same patient population.

Lenalidomide and Gemcitabine as First-line Treatment in Patients With Pancreatic Cancer

Phase I/II Study of Lenalidomide and Gemcitabine as First-line Treatment in Patients With Locally Advanced or Metastatic Pancreatic Cancer

In the phase I part of the study, the primary outcome is to determine the MTD and safety of the regimen lenalidomide and gemcitabine in combination. Data from all subjects who receive any study drug will be included in the safety analyses, according to the NCI CTCAE v3.0.

In the phase II part, the primary endpoint is to evaluate assessment of immunological reaction.The changes in immune responses at the end of cycle 1 (single lenalidomide or single gemcitabine) and cycle 2 (lenalidomide combined with gemcitabine) will be described in relation to baseline within the individual patient.

Progression-free survival (PFS) will be presented as time from start of therapy until clinical and/or radiological signs of progression of the disease by treatment group together.

Survival rate at 12 months will be presented as rate of patients still alive at 12 months after start of therapy by treatment group together.

Overall survival (OS) will be presented as time from start of therapy until death by treatment group together.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial Comparing EUS-guided Radiofrequency Ablation vs. EUS-guided Celiac Plexus Neurolysis	NCT03152487	Pancreatic Carc... Pancreatic Aden... Pancreatic Neop... Pancreatic Canc... Pancreatic Canc...	Celiac Plexus N... Radiofrequency ...	19 Years -	AdventHealth
Pancrelipase in People With Pancreatic Ductal Adenocarcinoma (PDAC)	NCT05642962	Metastatic Panc... Metastatic Panc... Metastatic Panc... Metastatic Panc... Pancreatic Carc... Pancreatic Carc... Pancreatic Carc... Pancreatic Canc... Pancreatic Canc... Pancreatic Canc... Pancreatic Canc... PDAC PDAC - Pancreat...	Pertzye	18 Years -	Memorial Sloan Kettering Cancer Center
Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors	NCT04659603	Breast Cancer M... Pancreatic Carc...	tusamitamab rav... Gemcitabine	18 Years -	Sanofi
Lenalidomide and Gemcitabine as First-line Treatment in Patients With Pancreatic Cancer	NCT01547260	Pancreatic Carc... Pancreatic Duct...	Gemzar Revlimid	19 Years -	Karolinska University Hospital

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