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Paused due to COVID. A determination was made to stop the study because it would be impossible to reach the 65% resection rate as outlined in the protocol.
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Surgical resection is the only potentially curative treatment for patients with pancreatic cancer. Patients with BRPC have tumors in close contact with the vasculature but not to the extent that resection is prohibited. Nonetheless, retrospective studies have shown that immediate resection in these patients is associated with an increased risk of positive margins, and a margin positive resection does not improve survival over that of patients with unresectable disease. Moreover, even in those patients where a successful resection is achieved, there is a high rate of early metastatic progression suggesting that micrometastatic disease is often present at diagnosis. Therefore neoadjuvant therapy is likely to improve outcomes in patients with BRPC to increase the likelihood of achieving a margin negative resection, provide early control of occult micrometastatic disease, and select those patients without systemic progression who would benefit from surgical resection.
Given the superior outcomes with FOLFIRINOX and the potential for improved local response with SBRT, the investigators propose to evaluate the efficacy of pre-operative modified FOLFIRINOX followed by SBRT in patients with borderline resectable pancreatic adenocarcinoma. The investigators hypothesize that pre-operative modified FOLFIRINOX followed by SBRT will improve the rate of R0 resections compared to historical controls treated with standard gemcitabine-based chemotherapy and fractionated radiation prior to surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| patients with borderline resectable pancreatic adenocarcinoma | Experimental | Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| neoadjuvant mFOLFIRINOX | Drug | Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With and Without R0 Resection | The primary outcome of this study is the R0 resection count of patients with BRPC treated with neoadjuvant mFOLFIRINOX and SBRT. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. When the study results were entered, rate was replaced with count as the manner in which these data were summarized. | Up to 40 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Response to Neoadjuvant Therapy Using RECIST | Response to treatment will be assessed by the treating physicians and investigators according to RECIST version 1.1. Counts of participants' RECIST category at their final visit up to 40 weeks below are provided. Per Response Evaluation Criteria In Solid TumorsCriteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
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Inclusion Criteria:
Histologically confirmed pancreatic adenocarcinoma
Borderline resectable pancreatic adenocarcinoma, determined centrally by review of a diagnostic CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist, or as determined by EUS, and defined according to the NCCN consensus guidelines
ECOG Performance Status of 0-1
Age > 18
Laboratory parameters as follows:
Able to have fiducials placed in the pancreas
Patients who received chemotherapy >5 years ago for malignancies other than pancreatic cancer are eligible
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kimberly Johung, MD, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Smilow Cancer Hospital | New Haven | Connecticut | 06510 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Patients With Borderline Resectable Pancreatic Adenocarcinoma | Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist. neoadjuvant mFOLFIRINOX: Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes. Stereotactic body radiotherapy (SBRT): Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Of 11 patients, 9 were eligible to be enrolled.
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients With Borderline Resectable Pancreatic Adenocarcinoma | Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist. neoadjuvant mFOLFIRINOX: Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes. Stereotactic body radiotherapy (SBRT): Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With and Without R0 Resection | The primary outcome of this study is the R0 resection count of patients with BRPC treated with neoadjuvant mFOLFIRINOX and SBRT. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. When the study results were entered, rate was replaced with count as the manner in which these data were summarized. | Posted | Count of Participants | Participants | Up to 40 weeks |
|
Up to 40 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Patients With Borderline Resectable Pancreatic Adenocarcinoma | Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist. neoadjuvant mFOLFIRINOX: Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes. Stereotactic body radiotherapy (SBRT): Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kimberly L. Johung, MD, PhD Associate Professor of Therapeutic Radiology | Yale School of Medicine | (203) 200-2008 | kimberly.johung@yale.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 16, 2020 | Aug 11, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
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| ID | Term |
|---|---|
| D000077150 | Oxaliplatin |
| D000077146 | Irinotecan |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
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|
|
| Stereotactic body radiotherapy (SBRT) | Drug | Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy. |
|
| Up to 40 weeks |
| Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy | A pathologic complete response is defined as the absence of residual invasive disease at the completion of the neoadjuvant treatment. This was performed only in those that had R0 resection performed. | Up to 40 weeks |
| Number of Participants With and Without Recurrence | Number of participants with and without recurrence following surgery. This outcome was updated when the results were entered. | Up to 40 weeks |
| Number of Participants: Progression Free Survival | Presented are count of patients that had experienced either progression free survival or disease progression through the follow up period. | Up to 2 years |
| Number of Participants: Overall Survival | Presented are counts of patients that we either deceased or not deceased at the end of the follow up period. | Up to 2 years |
| Grade 3 or Greater Acute and Late Gastrointestinal Toxicity | To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation. This outcome was clarified when results were entered. The number of patients that experienced at least 1 grade 3 (or greater) event are presented. | Up to 40 weeks |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Number of Participants Response to Neoadjuvant Therapy Using RECIST | Response to treatment will be assessed by the treating physicians and investigators according to RECIST version 1.1. Counts of participants' RECIST category at their final visit up to 40 weeks below are provided. Per Response Evaluation Criteria In Solid TumorsCriteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Posted | Count of Participants | Participants | Up to 40 weeks |
|
|
|
| Secondary | Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy | A pathologic complete response is defined as the absence of residual invasive disease at the completion of the neoadjuvant treatment. This was performed only in those that had R0 resection performed. | Only patients with R0 resection had pathologic response assesssed. | Posted | Count of Participants | Participants | Up to 40 weeks |
|
|
|
| Secondary | Number of Participants With and Without Recurrence | Number of participants with and without recurrence following surgery. This outcome was updated when the results were entered. | This population includes the 8 of 9 patients that experienced disease progression. | Posted | Count of Participants | Participants | Up to 40 weeks |
|
|
|
| Secondary | Number of Participants: Progression Free Survival | Presented are count of patients that had experienced either progression free survival or disease progression through the follow up period. | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| Secondary | Number of Participants: Overall Survival | Presented are counts of patients that we either deceased or not deceased at the end of the follow up period. | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| Secondary | Grade 3 or Greater Acute and Late Gastrointestinal Toxicity | To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation. This outcome was clarified when results were entered. The number of patients that experienced at least 1 grade 3 (or greater) event are presented. | Posted | Count of Participants | Participants | Up to 40 weeks |
|
|
|
| 6 |
| 9 |
| 6 |
| 9 |
| 9 |
| 9 |
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | Systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Malaise | General disorders | Systematic Assessment |
|
| Hepatobility disorders - Other, specify | Hepatobiliary disorders | Systematic Assessment | Jaundice/ Elevated bilirubin |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | Systematic Assessment |
|
| Infections and infestations - Other, specify | Infections and infestations | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Injury, poisoning and procedural complications - Other, specify | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Investigations - Other, specify | Investigations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Weight gain | Investigations | Systematic Assessment |
|
| Weight loss | Investigations | Systematic Assessment |
|
| White blood cell decreased | Investigations | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Amnesia | Nervous system disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Nervous system disorders - Other, specify | Nervous system disorders | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
|
| Reversible posterior leukoencephalopathy syndrome | Nervous system disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | Systematic Assessment |
|
| Urine discoloration | Renal and urinary disorders | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Ear and labyrinth disorders - Other, specify | Ear and labyrinth disorders | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Rectal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Oral dysesthesia | Gastrointestinal disorders | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Gait disturbance | General disorders | Systematic Assessment |
|
| General disorders and administration site conditions - Other, specify | General disorders | Systematic Assessment |
|
| Irritability | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Edema limbs | General disorders | Systematic Assessment |
|
| Infusion related reaction | General disorders | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | Systematic Assessment |
|
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | Systematic Assessment |
|
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| D004066 |
| Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D006571 |
| Heterocyclic Compounds |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |