Neoplasms

All Conditions

Symptoms and General Pathology

Adenocarcinoma

Disease Progression

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Hypoglycemic Agents

All Drugs and Chemicals

Metformin

All patients will receive metformin 500 mg per oral twice daily with food for at least 7 days, until 2 days prior to surgery. Metformin therapy should be discontinued 2 days before surgery to reduce the risk of lactic acidosis associated with fasting.

In the event of any grade 2 toxicities (with the exception of hyperglycemia), metformin will be withheld until improvement to ≤ grade 1, then restarted at a dose of 500 mg daily. In the event of grade ≥ 3 toxicities related to metformin, treatment will be discontinued. Metformin therapy will also be discontinued if serum lactate levels are above normal values.

Metformin Hydrochloride 500Mg Tablet

Daniel J Renouf, MD

Hui-li Wong, MD

This is a single arm, non-randomized phase II study of neoadjuvant metformin in resectable PDAC. Twenty patients will be enrolled and treated with metformin 500 mg BD for a minimum of 7 days, until 2 days prior to surgery. Patients will undergo laboratory investigations at baseline, prior to surgery and 4-10 weeks after surgery. Patients eligible for and consented to the optional MRI substudy will undergo diffusion-weighted MRI 1 to 14 days before surgery.

At surgery, resected tumour and normal tissue will be collected and banked. FFPE specimens will be used for sectioning, histological analysis and IHC for Ki67 (cell proliferation marker), pAMPK, ACC targets, p53 and mTOR targets, apoptotic markers (Bax, Bcl-2, caspases 3, 8 and 9). Fresh frozen tumour and matched normal tissue samples will be used for western blot analysis of insulin and IGF receptors, total and activated ERK and Akt, and RNAseq analysis. Pre-metformin biopsy samples will be retrieved for molecular analysis.

Fasting blood samples at baseline and before surgery will be analyzed for glucose and insulin levels. Plasma and whole blood will also be processed and banked for circulating tumour DNA analysis. Urine samples will be sent for metabolomic profiling.

The Effects of Neoadjuvant Metformin on Tumour Cell Proliferation and Tumour Progression in Pancreatic Ductal Adenocarcinoma

Assessment of Ki-67 fraction as assessed by IHC of pre- and post-metformin tumour samples.

Proportion of patients with R0 resections.

The marker of glucose and insulin metabolism will be reported with pre- and post-metformin values compared.

HOMA index is calculated from serum glucose and insulin. The marker of glucose and insulin metabolism will be reported with pre- and post-metformin values compared.

The clinical marker will be reported with pre- and post-metformin values compared.

Serum and urine metabolomic profile.

Comparison of metabolite levels in pre-and post-metformin samples.

To investigate the molecular signatures associated with metformin response

Comparison of gene expression in pre-metformin biopsy samples and post-metformin resected tumour samples. Expression of altered genes to be validated by IHC in tumour sections.

To assess the presence of ctDNA in resectable PDAC, and dynamic changes following treatment with metformin and surgical resection

Proportion of patients with detectable plasma ctDNA at baseline. Comparison of values pre- and post-metformin and 4-10 weeks after surgery.

To explore the correlation between apparent diffusion coefficient (ADC) on MRI and pathologic findings.

ADC values will be individually compared to tumour differentiation and Ki-67 fraction on pathologic examination.

Pancreatic Cancer Canada

BC Cancer Foundation

British Columbia Cancer Agency

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Pancreatic Cancer

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Gemcitabine

Paclitaxel

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Albumin-Bound Paclitaxel

Cisplatin

Oxaliplatin

Folic Acid

Folfirinox

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Patients receive mFOLFIRINOX for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.

Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months in the absence of disease progression or unacceptable toxicity.

Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors

Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors

Nab-paclitaxel

Radiation Therapy

Eugene J Koay

This is a phase II study using the Bayesian platform design. There are three clinical stage groups of localized pancreatic cancer: resectable, borderline resectable, and locally advanced disease. Each stage group will have a defined standard of care chemotherapy regimen for a control arm, serving as a basis of comparison. Each group may have one or more experimental arms. Experimental arms may be added to the platform over time, and the effects of the experimental treatments will be tested against the controls for each group.

PRIMARY OBJECTIVES:

I. To estimate major pathological response rate. (Resectable and borderline resectable groups \[treatment naive or previously treated\]) II. To estimate 6-month disease control rate. (Locally advanced groups \[treatment naive or previously treated\])

SECONDARY OBJECTIVES:

I. To measure progression free survival and overall survival. (Resectable and borderline resectable groups \[treatment naive or previously treated\]) II. To measure progression free survival and overall survival. (Locally advanced groups \[treatment naive or previously treated\])

EXPLORATORY OBJECTIVES:

I. To benchmark tissue acquisition protocols for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) analysis in pancreatic ductal adenocarcinoma (PDAC).

II. To demonstrate concordance of cell free DNA detected mutations to those detected in the tumor-derived DNA in PDAC.

III. To demonstrate response through exosome and circulating tumor DNA. IV. To demonstrate response through the quantification of the immune activation by analyzing T and B cells, peripheral blood mononuclear cells, and tissue biopsies.

V. To derive organoids from human PDAC and measure drug response in vitro. VI. To analyze the tumor microenvironment through immunohistochemistry (IHC) and hypoxia staining.

VII. To associate prognosis of patients with baseline and follow-up quantitative computed tomography (CT) image based analysis.

VIII. To associate clinical and pathological outcomes of patients with changes in radiomic measurements.

IX. To correlate quality of life for patients on standard and experimental therapies with laboratory, radiological, pathological, and clinical characteristics.

OUTLINE:Patients are assigned to different groups, and each group has a control arm. Within each group, the patient will be randomized to the appropriate control or an experimental arm. The control arms for the groups are:

Control arm for Group I (Treatment-naive resectable PDAC): Patients receive fluorouracil, irinotecan, leucovorin, and oxaliplatin (mFOLFIRINOX) for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.

Control arm for Group II (Previously-treated resectable PDAC): Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months in the absence of disease progression or unacceptable toxicity.

Control arm for Group III (Treatment-naive borderline resectable PDAC): Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Control arm for Group IV (Previously-treated borderline resectable PDAC): Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Control arm for Group V (Treatment-naive locally advanced PDAC): Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Control arm for Group VI (Previously-treated locally advanced PDAC): Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

After completion of study treatment, patients are followed up every 16 weeks.

New and Emerging Therapies for the Treatment of Resectable, Borderline Resectable, or Locally Advanced Pancreatic Cancer, PIONEER-Panc Study

PIONEER-Panc: Phase II Investigations of New and Emerging Therapies for Pancreatic Cancer

Major pathological response is any patient who has grade I or II treatment response. Grade I - 0% residual tumor cells in the specimen (pathologic complete response, grade II - 1 to \< 5% residual tumor cells in the specimen.

Measured as the proportion of patients without progression.

Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Gastrointestinal Agents

Pancrelipase

Pancreatin

Patients will be treated with NALIRINOX, a combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin. Treatment regimen will consist of 8 cycles of neoadjuvant NALIRINOX prior to surgery and trial duration is expected to be 24 months.

NALRINOX: combination of three chemotherapy agents: 5- FU/LV, nal-IRI, and oxaliplatin

NALRINOX combination

Antonio Cubillo, MD

Pancreatic cancer has an unfavorable prognosis with a reduced possibility of long-term survival. The only treatment with curative potential is surgery, but it is only possible in 15-20% of cases.

There are patients with clear criteria for surgical entry, others at the limit of the possibility of surgery, and patients with such advanced disease (either locally or with metastasis) that surgery is not indicated.

The objective of neoadjuvant chemotherapy treatment (received before surgery) is to reduce the tumor before surgery and reduce the risk of subsequent metastases and local recurrences, in borderline tumors or those resectable with high-risk criteria.

The FOLFIRINOX scheme, composed of 5-fluorouracil / folinic acid, oxaliplatin and irinotecan, is recommended as neoadjuvant treatment, but the response is still low. This study will use a modified FOLFIRINOX (NALIRINOX) regimen with a form of irinotecan attached to liposomes that allows greater action on tumor cells.

Mutations in the KRAS gene are associated with a greater growth capacity of tumor cells and are present in 90% of pancreatic cancers in advanced stages. They would be less frequent in earlier phases but little is known about the impact that chemotherapy treatment and subsequent surgery could have on the increase or decrease of these mutations, as well as their implication. The follow-up of these mutations with repeated pancreatic biopsies is not viable, but it can be monitored by simple blood samples in which the genetic material of the tumor can be analyzed.

This study is a multicenter, single-arm, interventional, open-label, non-randomized, phase II clinical trial, to evaluate the association of KRAS mutational load and histological tumour response after chemotherapy treatment in patients with PDAC. Due to its single-arm design patients will be assigned to a single group (non-randomized) and there will be no masking (open-label).

Nalirinox Neo-pancreas RAS Mut ctDNA Study

A Phase II Trial to Assess the Evolution of KRAS Mutation Load by Liquid Biopsy in Patients With Resectable Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant NALIRINOX

Syntax for Science, S.L

Fundación de investigación HM

FOLFIRINOX consists of the following combination of drugs:

1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle
2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle
3. Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle
4. 5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle.
5. 5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

FOLFIRINOX consists of the following combination of drugs:

1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle
2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle
3. Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 4.5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle.

5.5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

FOLFIRINOX

Michael House, M.D.

The primary objective of this study is to evaluate the rate of pathologic complete response to neoadjuvant FOLFIRINOX in patients with resectable pancreatic cancer using a tissue collection component.

A Phase II Study of Neoadjuvant FOLFIRINOX

A Phase II Study of Neoadjuvant FOLFIRINOX in Patients With Resectable Pancreatic Ductal Adenocarcinoma With Tissue Collection

Pathologic complete response was evaluated using MRI or CT and Evan's criteria for pathologic response following neoadjuvant therapy:

I: \<10% to no tumor cells destroyed IIa: 10-50% of tumor cells destroyed IIb: 50-90% of tumor cells destroyed III: \>90% of tumor cells destroyed IIIM: sizable pools of cellular mucin IV: No viable tumor cells (complete pathologic response) IVM: Acellular pools of mucin

Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event with grade 3 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

The percentage of patients who successfully underwent surgery after neoadjuvant FOLFIRINOX and its 95% confidence interval will be provided.

The percentage of patients with a final margin status of R0 after resection of their primary tumor and its 95% confidence interval will be provided. R0 resection indicates a microscopically margin-negative resection, in which no cancer cells seen microscopically at the primary tumor site.

Disease free survival is defined as the time from on study date to evidence of tumor recurrence or death from any cause. Patients who remained alive and disease free were censored at their date of last disease evaluation.

Overall survival was defined as the time from on study date to death due to any cause. Patients who remained alive were censored at their last known alive date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.

Measured by RECIST v1.1 Complete response: Disappearance of all target lesions Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter

The percentage of patients with objective response and its 95% confidence interval will be provided.

Measured by RECIST v1.1

Complete response: Disappearance of all target lesions Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Stable disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started

The percentage of patients with objective response and its 95% confidence interval will be provided.

Indiana University

Assistant Professor of Clinical Medicine

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Amikar Sehdev

All patients who received at least two doses of FOLFIRINOX (unless treatment-related toxicity precluded additional doses) and had at least one post-baseline assessment or died before any evaluation.

Percentage of Patients With Pathologic Complete Response

All patients who received at least one dose of FOLFIRINOX.

Number of Patients With Treatment-Related Adverse Events Grade 3 or Above

Percentage of Patients Who Successfully Underwent Surgery After Neoadjuvant FOLFIRINOX

Rate of R0 Resection

Disease Free Survival

Overall Survival

Patients who received four treatments of FOLFIRINOX and had at least one post-baseline assessment.

Objective Response Rate (Percentage of Patients With Complete Response or Partial Response)

Disease Control Rate (Percentage of Patients With Complete Response, Partial Response, or Stable Disease)

Overall Study

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Anti-Infective Agents

Pyrvinium

Anthelmintics

Antiparasitic Agents

Patients receive pyrvinium pamoate PO QD for 3 days in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

Pyrvinium Pamoate

Harish Lavu, MD

This phase I trial studies the side effects and best dose of pyrvinium pamoate for the treatment of pancreatic ductal adenocarcinoma that cannot be removed by surgery (resectable). Pyrvinium pamoate may slow down tumor growth and help patients live longer.

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of pyrvinium pamoate (PP), dosed orally, in patients with pancreatic ductal adenocarcinoma (PDAC) that are surgical candidates.

SECONDARY OBJECTIVE:

I. Assessment of PP's pharmacokinetic and pharmacodynamic (PK/PD) profile and bioavailability in humans.

OUTLINE: This is a dose-escalation study.

Patients receive pyrvinium pamoate orally (PO) once daily (QD) for 3 days in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

After completion of study treatment, patients are followed up for 30 days and then every week for up to 4 weeks.

A Study to Determine if the Drug, Pyrvinium Pamoate, is Safe and Tolerable in Patients With Pancreatic Cancer

A Phase I Dose Escalation Study Using Pyrvinium Pamoate Targeting HuR in Pancreatic Ductal Adenocarcinoma

Considered any grade 3 or higher adverse event due to the drug itself or delay of surgery. Research coordinator will call patient every day to monitor for DLTs.

Will be assessed using liquid chromatography followed by mass spectrometry (LC/MS).

Thomas Jefferson University

Recurrence

Disease Attributes

Standardized surveillance strategy with routine imaging and serum tumor marker testing.

Non-standardized surveillance strategy according to current clinical practice.

Standardized 3-monthly surveillance with routine imaging and serum tumor marker testing.

Standardized surveillance

I. Q. Molenaar, MD, PhD

H. C. van Santvoort, MD, PhD

M. G.H. Besselink, MD, PhD

L. A. Daamen, MD, PhD

A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'trials within cohorts' (TwiCs) design in which the effect of a standardized surveillance, with serial tumor marker testing and routine imaging, compared to current non-standardized practice, on overall survival and quality of life in patients with primary resected PDAC is investigated. The most important secondary endpoint is quality of life. Other secondary endpoints are clinical and radiological patterns of PDAC recurrence, the compliance of patients to our standardized follow-up strategy, the impact of a standardized surveillance on (eligibility for) additional treatment, and the tolerance of additional treatment. The need for this clinical trial is emphasized by the the emergence of more potent local and more effective systemic treatments for PDAC recurrence, leading to a rising interest in early diagnosis by a standardized approach to follow-up with routine imaging and serial serum tumor marker testing.

Rationale: Radical resection combined with (neo)adjuvant chemotherapy offers the best chances for long-term survival for patients with resectable localized pancreatic ductal adenocarcinoma (PDAC). However, even after radical resection, almost all patients will experience local and/or distant disease recurrence after sufficient follow-up, mostly within 2 years. There is a lack of evidence based effective therapeutic options for the significant group of patients with local recurrence only, in terms of improved survival and/or quality of life. In the case of metastatic disease effective chemotherapy has shown to improve survival, but with a median gain survival of 3-4 months. Taken together, this had led to a hesitant attitude towards postoperative recurrence-focused follow-up. Therefore, in most European countries, including the Netherlands, a standardized approach to follow-up after surgery for PDAC is lacking. Furthermore, current PDAC guidelines regarding follow-up are based on expert opinion and other low-level evidence. However, the emergence of more potent local and more effective systemic treatments for PDAC has led to a rising interest in early diagnosis of PDAC recurrence. To detect PDAC recurrence at an early stage and identify patients with good performance status who are most likely to benefit from additional (experimental) treatment, a standardized approach to follow-up with routine imaging and serial serum tumor marker testing is needed. To determine whether early detection of recurrence can lead to improved survival and quality of life, further studies are warranted.

Objective: The main objective is to evaluate the impact of a standardized surveillance, with serial tumor marker testing and routine imaging, on overall survival and quality of life in patients with primary resected PDAC, compared to current non-standardized practice.

Study design: A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'trials within cohorts' (TwiCs) design.

Study population: PACAP-participants with histologically confirmed radical resection (R0-R1) of PDAC, who provided informed consent for being randomized in future studies.

Interventions: Standardized surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT-) imaging of chest and abdomen every 3 months during the first 2 years after surgery.

Comparison: Non-standardized clinical follow-up.

Endpoints: The main study endpoint is overall survival. The most important secondary endpoint is quality of life. Other secondary endpoints are clinical and radiological patterns of PDAC recurrence, the compliance of patients to our standardized follow-up strategy, the impact of a standardized surveillance on (eligibility for) additional treatment, and the tolerance of additional treatment.

Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy

Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy: a Nationwide Randomized Controlled Trial

De-identified data generated during the RADAR-PANC trial will be made available to other researcher upon request from I.Q. Molenaar.

The interval between the date of PDAC resection and either death from any cause or last follow-up.

Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.

The percentage of patients that either accepts or refuses participation in the intervention-arm, i.e. is willing to undergo a standardized follow-up regime.

The interval between the date of PDAC resection and the date of first radiological signs of recurrence, or last follow-up if recurrence is not observed.

e.g. poor condition, patients wish, deteriorated condition, progressive disease, advise treating clinician, death, wait-and-see, age.

Dutch Pancreatic Cancer Group (DPCG)

UMC Utrecht

Principal Investigator

Patients receive NBTXR3 IT on day 1. Patients then undergo 15 fractions of radiation therapy between days 15-43 in the absence of disease progression or unacceptable toxicity.

Hafnium Oxide-containing Nanoparticles NBTXR3

To find the recommended dose of NBTXR3 that can be given in combination with radiation therapy to patients with pancreatic cancer. To learn if the dose NBTXR3 found in Part 1 can help to control the disease.

PRIMARY OBJECTIVE:

• To determine the recommended phase II dose (RP2D) of NBTXR3 activated by radiotherapy in subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma.

SECONDARY OBJECTIVES:

* To evaluate the safety and feasibility of NBTXR3 intratumoral injection activated by radiotherapy in locally advanced or borderline-resectable pancreatic ductal adenocarcinoma
* To evaluate the anti-tumor response of NBTXR3 intratumoral injection activated by radiotherapy in subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma
* To evaluate time-to-event outcomes in subjects with locally advanced or borderline-resectable pancreatic ductal adenocarcinoma

EXPLORATORY OBJECTIVES:

* To evaluate the body kinetic profile of intratumorally injected NBTXR3.
* To evaluate time to event outcomes for subjects with clinical staging of locally advanced, unresectable disease.
* To evaluate resectability conversion rates.
* To evaluate surgical outcomes in subjects who undergo surgery after radiation therapy.
* To associate radiomic measurements with outcomes.
* To evaluate biomarkers of response in subjects treated with NBTXR3/RT.

OUTLINE: This is a dose-escalation study of NBTXR3.

Patients receive NBTXR3 intratumorally (IT) on day 1. Patients then undergo 15 fractions of intensity modulated radiation therapy (IMRT) between days 15-43 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.

NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer

Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma

Will evaluation of the time-course dependent presence of hafnium in blood and urine following NBTXR3 intratumoral injection.

Defined as the proportion of patients without progression 6 months post NBTXR3 injection.

Resection status as assessed macroscopically by surgeon R0- Macroscopically complete tumor removal with negative microscopic surgical margins, R1- Macroscopically complete tumor removal with positive microscopic margins (any or all), and R2- Macroscopically incomplete tumor removal with known or suspected residual gross disease.

Any grade \>= 3 adverse event related to NBTXR3 and/or radiation therapy. Any toxicity (grade \>= 3) that is at least possibly related to study drug (NBTXR3) is a DLT. Adverse events will be scored based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0).

MTD will be determined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate 30%.

Feasibility refers to the ability to do intratumoral injection of NBTXR3. The outcome for each patient would be "feasible" or "not feasible."

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Effects of Neoadjuvant Metformin on Tumour Cell Proliferation and Tumour Progression in Pancreatic Ductal Adenocarcinoma	NCT02978547	Resectable Panc...	Metformin Hydro...	18 Years -	British Columbia Cancer Agency
New and Emerging Therapies for the Treatment of Resectable, Borderline Resectable, or Locally Advanced Pancreatic Cancer, PIONEER-Panc Study	NCT04481204	Borderline Rese... Locally Advance... Resectable Panc...	Cisplatin Fluorouracil Gemcitabine Irinotecan Leucovorin Nab-paclitaxel Oxaliplatin Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Nalirinox Neo-pancreas RAS Mut ctDNA Study	NCT04010552	Resectable Panc...	NALRINOX combin...	18 Years -	Fundación de investigación HM
A Phase II Study of Neoadjuvant FOLFIRINOX	NCT02178709	Resectable Panc...	FOLFIRINOX	18 Years -	Indiana University
New and Emerging Therapies for the Treatment of Resectable, Borderline Resectable, or Locally Advanced Pancreatic Cancer, PIONEER-Panc Study	NCT04481204	Borderline Rese... Locally Advance... Resectable Panc...	Cisplatin Fluorouracil Gemcitabine Irinotecan Leucovorin Nab-paclitaxel Oxaliplatin Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
A Study to Determine if the Drug, Pyrvinium Pamoate, is Safe and Tolerable in Patients With Pancreatic Cancer	NCT05055323	Resectable Panc... Stage 0 Pancrea... Stage I Pancrea... Stage IA Pancre... Stage IB Pancre... Stage II Pancre... Stage IIA Pancr... Stage IIB Pancr...	Pyrvinium Pamoa...	18 Years -	Thomas Jefferson University
Recurrent Disease Detection After Resection of Pancreatic Adenocarcinoma Using a Standardized Surveillance Strategy	NCT04875325	Resectable Panc... Recurrent Pancr...	Standardized su...	18 Years -	UMC Utrecht
NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer	NCT04484909	Borderline Rese... Locally Advance... Resectable Panc... Stage III Pancr...	Hafnium Oxide-c... Radiation Thera...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for resectable pancreatic ductal adenocarcinoma