Neoplasms

All Conditions

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Diabetes Mellitus

Weight Loss

Pancreatic Neoplasms

Body Weight

Hyperglycemia

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Two interventions are performed:

1. Have Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score calculated, and if Score is \>0,
2. Have abdominal imaging performed.

Passive follow-up by electronic medical record for study endpoints of pancreatic cancer diagnosis.

ENDPAC is a model to risk-stratify patients with new onset diabetes and hyperglycemia for PDAC. Score is calculated using i) age, ii) change, over past year, in body weight and iii) change, over past year, in glucose/HbA1c values obtained from the electronic medical record.

Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score

Using computerized tomography (CT) scan or magnetic resonance imaging (MRI), if CT scan is contra-indicated, patients with a high ENDPAC score (\>0) are approached for informed consent to participate in the imaging intervention. Imaging (CT scan) is performed at up to two time points, study baseline and approximately 3-9 months following the first imaging study.

Abdominal imaging

Suresh Chari, MD

Anirban Maitra, MBBS

Bechien Wu, MD

Avinash Kambadakone-Ramesh, MD, FRCR

Ziding Feng, PhD

Jackie Dahlgren

The Early Detection Initiative for Pancreatic Cancer is a multi-center randomized controlled trial to determine if algorithm-based screening in patients with new onset hyperglycemia and diabetes can result in earlier detection of pancreatic ductal adenocarcinoma.

The Early Detection Initiative (EDI), is designed to evaluate if imaging at the time of new onset hyperglycemia and diabetes, especially at its earliest discovery through passive surveillance of the electronic medical record (EMR), results in earlier detection of pancreatic ductal adenocarcinoma (PDAC).

Eligible patients are identified and enrolled based on a first-time elevation in fasting blood glucose or glycated hemoglobin (HbA1c) to the level indicating diabetes as derived from records in their EMR. All enrolled patients are randomized to either the Observational Arm or Intervention Arm of the study. Patients randomized to the Intervention Arm have Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score calculated using age, body weight and glucose or glycated hemoglobin values in their EMR. Patients with high ENDPAC score (\>0) are approached for informed consent to participate in up to two imaging studies by computerized tomography (CT) scan or magnetic resonance imaging (MRI). In addition to imaging, participants will be asked to complete study questionnaires and participate in serial blood collection at up to five time points. Blood samples collected in the EDI study will contribute to the National Institutes of Health (NIH) National Cancer Institute (NCI) biorepository located at the Frederick National Laboratory for Cancer Research facility. Patients in both study arms are followed for development of PDAC.

This study is performed at locations with broad (institutional) consent for use of patient EMR information for research studies. Passive follow-up by EMR will occur for five years following enrollment. Any patient that has declined participation in EMR-based research at the institution is not included in the study.

Randomized controlled trial with post-randomization consent

Early Detection Initiative for Pancreatic Cancer

A Randomized Controlled Trial of Algorithm-based Screening in Patients With New Onset Hyperglycemia and Diabetes for Early Detection of Pancreatic Ductal Adenocarcinoma (Early Detection Initiative (EDI) for Pancreatic Cancer)

Determine if algorithm-based screening in new onset hyperglycemia and diabetes (NOD) results in earlier detection of pancreatic ductal adenocarcinoma (PDAC) as evidenced by a lower proportion of Stage III/IV disease at the time of PDAC diagnosis in intervention vs observation arm.

Determine if Intervention results in earlier detection of PDAC defined as a smaller proportion of unresectable disease.

Determine if Intervention results in earlier detection of PDAC defined as less Stage IV disease.

Determine if Intervention results in earlier detection of PDAC defined as a smaller proportion with advanced pancreatic cancer symptoms.

Estimate the risk of PDAC in NOD and Enriching New-onset Diabetes (or hyperglycemia) for Pancreatic Cancer (ENDPAC) subgroups.

Determine the magnitude of over diagnosis due to imaging intervention of NOD.

Determine, on imaging in NOD, the proportion with incidental findings that require clinical workup.

Contribute blood biospecimens to a previously established NOD cohort biobank for future biomarker validation studies.

Determine if symptoms of depression and anxiety are early indicators of PDAC.

Fred Hutchinson Cancer Center

National Institutes of Health (NIH)

Pancreatic Cancer Action Network

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Pancrelipase

Pancreatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Nab-paclitaxel and gemcitabine, for R-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Nab-paclitaxel and gemcitabine, for BR-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Nab-paclitaxel and gemcitabine, for R-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Nab paclitaxel

Nab-paclitaxel and gemcitabine, for BR-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Wells Messersmith, MD

The objective of this study is to estimate the R0 resection rate in patients with Resectable Pancreatic Ductal Adenocarcinoma (R-PDAC) as well as those with Resectable Pancreatic Ductal Adenocarcinoma (BR-PDAC) independently in response to neoadjuvant sequential therapy of combination nab-paclitaxel and gemcitabine followed by stereotactic body radiotherapy (SBRT).

Patients in both cohorts will receive a total of 3 cycles of neoadjuvant combination chemotherapy of nab-paclitaxel and gemcitabine, followed by re-staging CT scan, if re-staging CT does not show evidence of metastatic disease. Patients will receive SBRT and definitive surgical resection. Subsequently, patients will receive 3 cycles of adjuvant combination chemotherapy of nab-paclitaxel and gemcitabine. Each cycle of combination chemotherapy will be a total of 4 weeks. Patients will be evaluated for response at completion of the 3 cycles of neoadjuvant combination chemotherapy with CT scans of chest, abdomen and pelvis. Patients will undergo surveillance CT scan at 3-month intervals until evidence of disease progression.

Perioperative Therapy for Resectable and Borderline-Resectable Pancreatic Adenocarcinoma With Molecular Correlates

Perioperative Therapy for Resectable Pancreatic Adenocarcinoma and Borderline Resectable Pancreatic Adenocarcinoma With Molecular Correlates

R0 resection rates will be measured in patients with resectable PDAC and with patients with borderline-resectable PDAC, independently in response to neoadjuvant sequential therapy of combination of nab-paclitaxel and gemcitabine and SBRT, as perioperative therapy. R0 resection is determined by macroscopically complete tumor removal with negative microscopic surgical margins in the bile duct, pancreatic parenchyma, and superior mesenteric artery (SMA).

Overall survival will be assessed for all participants

Celgene Corporation

Criterium, Inc.

University of Colorado, Denver

Academic Thoracic Oncology Medical Investigators Consortium

Nab-paclitaxel and gemcitabine, for R-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Nab-paclitaxel and gemcitabine for R-PDAC Patients: Nab-paclitaxel and gemcitabine, for R-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Nab-paclitaxel/Gemcitabine for R-PDAC

Nab-paclitaxel and gemcitabine, for BR-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Nab-paclitaxel and gemcitabine for BR-PDAC Patients: Nab-paclitaxel and gemcitabine, for BR-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Nab-paclitaxel/Gemcitabine for BR-PDAC

Nab-paclitaxel and gemcitabine, for R-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Nab paclitaxel: Nab-paclitaxel and gemcitabine, for R-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Gemcitabine: Nab-paclitaxel and gemcitabine, for BR-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Nab-paclitaxel and Gemcitabine for R-PDAC

Nab-paclitaxel and gemcitabine, for BR-PDAC patients enrolled in this trial, will be given in combination as neoadjuvant combination chemotherapy, followed by SBRT. This is will be followed up by surgical resection and an additional combination chemotherapy of nab-paclitaxel and gemcitabine as adjuvant chemotherapy.

Nab paclitaxel: Nab-paclitaxel and gemcitabine, for R-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Gemcitabine: Nab-paclitaxel and gemcitabine, for BR-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.

Nab-paclitaxel and Gemcitabine for BR-PDAC

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

R0 Resection Rates in Each Cohort as Measured by Macroscopically Complete Tumor Removal With Negative Microscopic Surgical Margins

Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v.4.03

Median Overall Survival

Overall Study

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Capecitabine

Levoleucovorin

Cisplatin

Folic Acid

Folinic Acid

Folate

Vitamin B9

cisplatin 30 mg/m2 every 2 weeks, nab-paclitaxel 150 mg/m2 every 2 weeks, gemcitabine 800 mg/m2 every 2 weeks, capecitabine 1250 mg/m2/day (for 28 consecutive days) in 28-day cycles administered for 4 cycles (4 months).

irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, folinic acid at a fixed dose of 400 mg/m2, fluorouracil continuous IV infusion 2.4 g/m2 over 46 hours in 14-day cycles administered for 8 cycles (4 months).

Allocated by second randomization after 4 months of chemotherapy to receive immediate surgery followed by 2 further months of the same chemotherapy

Allocated by second randomization after 4 months of chemotherapy to receive 2 further months of the same chemotherapy followed by surgery

Nab-paclitaxel, cisplatin and gemcitabine drugs will be administered on day 1 and 15 every 28 days. Capecitabine tablets will be taken orally on days 1 to 28, every 28 days

PAXG

Oxaliplatin, folinic acid, irinotecan and 5-Fluoruracil will be administered on day 1 and 15 every 28 days

mFOLFIRINOX

other two months of chemotherapy after surgery

short-course chemotherapy

other two months of chemotherapy before surgery

long-course chemotherapy

Michele Reni, MD

Maria Maddalena Valente, PhD

Angela Buonadonna, MD

Claudio Bellulo, MD

Nicola Silvestris, MD

Michele Simone, MD

Oronzo Brunetti, MD

Antonella Argentiero, MD

Barbara Merelli, MD

Michele Colledan, MD

Mariacristina Di Marco, MD

Riccardo Casadei, MD

Alberto Zaniboni, MD

Moh'd Abu Hilal, MD

Elisa Giommoni, MD

Lorenzo Antonuzzo, MD

Coratti Andrea, MD

Luca Faloppi, MD

Walter Siquini, MD

Luca Frassineti, MD

Silvia Bozzarelli, MD

Alessandro Zerbi, MD

Katia Bencardino, MD

Giovanni Ferrari, MD

Mario Scartozzi, MD

Adolfo Pisanu, MD

Roberto Ottonello, MD

Roberto Bianco, MD

Roberto Ivan Troisi, MD

Roberto Montalti, MD

Sara Lonardi, MD

Francesca Bergamo, MD

Letizzia Procacci, MD

Livio Blasi, MD

Valentina Palmisano, MD

Enrico Vasile, MD

Ugo Boggi, MD

Giampaolo Tortora, MD

Sergio Alfieri, MD

Alessandro Ferrero, MD

Massimo Di Maio, MD

Elisa Sperti, MD

Donatella Marino, MD

Marco Massani, MD

Adolfo Favaretto, MD

Cristina Nistri, MD

Donatella Iacono, MD

Gianpiero Fasola, MD

Alessandro Uzzau, MD

Sergio Intini, MD

Claudio Bassi, MD

Michele Milella, MD

Giuseppe Aprile, MD

The main aim of this study is to compare the efficacy of short-course versus long-course pre-operative chemotherapy with PAXG or mFOLFIRINOX in patients who receive a diagnosis of pancreatic ductal adenocarcinoma (PDAC) resectable or borderline resectable.

Pancreatic cancer is the seventh cause of death in cancer patients and more than 94% of affected patients die of cancer disease. In the majority of cases, the diagnosis is done at an advanced stage and only 10-20% of patients can be treated with a surgical resection. For this neoplasia, a radical resection may be an effective treatment. Nevertheless, results obtained with surgery alone are rather inadequate, showing a median survival of 12-14 months and 2-year survival of almost 20%: it seems evident the necessity to use complementary treatments in order to improve survival rate in this group of patients.

Pancreatic cancer can relapse locally, at the level of tumoral bed, of the regional lymph nodes, on the immediately adjacent peritoneal surface or on contiguous organs. Also, distant metastases are quite frequent, mainly to the liver, at the entire peritoneal surface and, rarely, to the extra-abdominal organs. The rapid appearance of these metastases after surgical resection strongly suggests the presence of subclinical metastatic diffusion at an early phase of the disease.

Currently, combination chemotherapy based on the mFOLFIRINOX regimen is considered the therapeutic standard in the adjuvant setting, in young and fit patients. Unfortunately, mFOLFIRINOX is burdened with strong haematological and extra-haematologic toxicity and just 2/3 of patients are able to complete the treatment. Recently, PAXG regimen \[(Cisplatin (P), Abraxane (A), Capecitabine (X), Gemcitabine (G)\] when compared to AG in randomized studies, showed an improvement in terms of progression-free survival (PFS) and overall survival in borderline resectable, locally advanced and metastatic patients. To date, several ongoing randomized trials are investigating the efficacy of perioperative or neoadjuvant strategies in early stage PDAC. Only few studies are available regarding neoadjuvant treatment: some are outdated, numerically inconsistent, retrospective, or not randomized. In this scenario, it aims to better investigate pre-operative therapeutic strategy.

For this purpose, two randomizations are planned.

1. FIRST RANDOMIZATION. Eligible patients will be randomized (1:1), stratifying by basal CA19.9 level (\<5 ULN vs ≥ 5ULN) and centre to receive:

   PAXG or mFOLFIRINOX for 4 months
2. SECOND RANDOMIZATION. Patients without progression or limiting toxicity after 4 months of the assigned chemotherapy in the study, will be randomized (1:1), stratifying by treatment assigned by the first randomization, to receive 2 further months of the same chemotherapy either BEFORE or AFTER surgery.

Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG (CASSANDRA TRIAL)

A Randomized Phase II Trial of Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG Regimen for Stage I-III Pancreatic Ductal Adenocarcinoma (PDAC)

to compare in terms of event free survival (EFS) the efficacy of PAXG to that of mFOLFIRINOX. EFS is defined as the time from randomization to: RECIST 1.1 progression \[At least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20 percent, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression\]; CA19.9 failure (defined as 2 consecutive increases of serum level ≥20 percent, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be.

to compare in terms of event free survival (EFS) the efficacy of 4 months pre-operative and 2 months postoperative chemotherapy to that of 6 months of pre-operative chemotherapy . EFS is defined as the time from randomization to: RECIST 1.1 progression \[At least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20 percent, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression\]; CA19.9 failure (defined as 2 consecutive increases of serum level ≥20 percent, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be.

the time between the date of the patient's enrollment and the death of the patient for any cause or the last time the patient was seen alive

Radiological response evaluation during the treatment by using RECIST 1.1 criteria

Biochemical response evaluation during the treatment by using this specific marker

The evaluation of surgical mortality and morbidity rate.

The evaluation of intra- and post-operative metastasis rate.

The evaluation of N0 and R0 resections rate.

The evaluation of drugs safety and tolerability by SAE report

Impact of treatment on quality of life assessed by the latest version of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30)

Impact of treatment on quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life scale for pancreatic cancer (EORTC QLQ - PAN26)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Early Detection Initiative for Pancreatic Cancer	NCT04662879	Hyperglycemia Diabetes Mellit... Pancreas Ductal...	Enriching New-o... Abdominal imagi...	50 Years - 85 Years	Pancreatic Cancer Action Network
Perioperative Therapy for Resectable and Borderline-Resectable Pancreatic Adenocarcinoma With Molecular Correlates	NCT02723331	Pancreatic Canc... Pancreatic Aden... Pancreas Ductal...	Nab paclitaxel Gemcitabine	18 Years - 101 Years	University of Colorado, Denver
Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG (CASSANDRA TRIAL)	NCT04793932	Pancreas Ductal...	PAXG mFOLFIRINOX short-course ch... long-course che...	18 Years - 75 Years	Associazione Italiana per lo Studio del Pancreas

Spots Global Cancer Trial Database for pancreas ductal adenocarcinoma