Pancreatic Adenocarcinoma Neoadjuvant Combination Chemotherapy and Stereotactic Body Radiation Therapy Before Surgery (PANCREAS)

• ClinicalTrials.gov Identifier: NCT04452461
• Recruitment Status: Not yet recruiting
• First Posted: June 30, 2020
• Last Update Posted: June 30, 2020
• Sponsor: Hamilton Health Sciences Corporation
• Information provided by (Responsible Party): Pablo Serrano, Hamilton Health Sciences Corporation

Tracking Information

• First Submitted Date: June 22, 2020
• First Posted Date: June 30, 2020
• Last Update Posted Date: June 30, 2020
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: May 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2020)

Proportion of patients eligible enrolled [ Time Frame: 18 months ]

Over an 18-month period The proportion of patients who complete the protocol (neoadjuvant therapy and pancreatectomy). As described, there are certain modifications of the neoadjuvant therapy protocol that are expected and allowed. The primary feasibility outcome will be one of the following:

• Stop, main study non-feasible: 1) estimated proportion of eligible patients enrolled <40% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) <40%.
• Continue with protocol modifications: 1) estimated proportion of eligible patients enrolled between 40-59% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) 40-59%.
• Continue without modification: 1) estimated proportion of eligible patients enrolled equal to or greater than 60% or estimated proportion of enrolled patients who complete the protocol (neoadjuv

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: June 29, 2020)

• Survival [ Time Frame: 24 months ]
  Defined as percentage of patients alive at two years from enrolment.
• Time to Progression [ Time Frame: 24 months from the initiation of chemotherapy (the length of the study) ]
  Defined as the duration of time from enrolment to time to radiological evidence of disease progression or recurrence or death, whichever comes first.
• Overall Complications from surgery [ Time Frame: From date of surgery (POD=0) up to 90 postoperative days (POD=90) ]
  Occurrence of any postoperative complication (major or minor) from surgery following each patient's hospital stay and up to 90 days from the initial operation.
• Pathological response to chemo-radiation treatment [ Time Frame: From the date of the first chemotherapy to the date of surgery (around 4 months) ]
  Pathological response to treatment will be classified as per protocol.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pancreatic Adenocarcinoma Neoadjuvant Combination Chemotherapy and Stereotactic Body Radiation Therapy Before Surgery
• Official Title: mFOLFIRINOX or Gemcitabine / Nab-paclitaxel and Stereotactic Body Radiation Therapy Followed by Pancreatectomy for Patients With Borderline Resectable Pancreatic Adenocarcinoma. A Pilot Feasibility Study.
• Brief Summary: This is a single-arm, single-center feasibility trial of patients with borderline resectable pancreatic adenocarcinoma receiving radiation therapy with Stereotactic body radiation therapy (SBRT) and chemotherapy with mFOLFIRINOX or gemcitabine / nab-paclitaxel followed by pancreatectomy.

Detailed Description

Borderline resectable pancreatic adenocarcinoma infiltrates into adjacent vascular structures to an extent such that complete macroscopic resection is technically feasible, but an R0 resection poses a challenge when surgery is the primary therapy. Therefore, a different management strategy may be beneficial.

The primary outcome of the PANCREAS trial is defined as the proportion of eligible patients enrolled in the study over an 18-month period and the proportion of patients who complete the protocol (neoadjuvant therapy and pancreatectomy). Certain modifications of the neoadjuvant therapy protocol are expected and allowed, and the primary feasibility outcome will be one of the following: stop, main study non-feasible; continue with protocol modifications; or continue without modification. A safety analysis will be performed after first 15 patients are enrolled and complete neoadjuvant therapy and surgery. Patients enrolled in this trial will undergo interventions in the following order: neoadjuvant chemotherapy, re-staging CT scan, SBRT, re-staging CT scan, pancreatectomy and adjuvant chemotherapy. Postoperative mortality will be recorded up to 90 days after surgery. Patients will be followed every four months with a CT scan of the chest/abdomen for two years after resection or until evidence of disease recurrence. Patients who do not undergo surgical resection will be followed for two years after accrual (duration of study period) or until evidence of disease progression or death.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Adenocarcinoma

Intervention

• Drug: mFOLFIRINOX
  mFOLFIRINOX, including: Oxaliplatin 85 mg/m2 IV over 2 hours, Leucovorin 400mg/m2 IV over 2 hours, Irinotecan at 150 mg/m2 IV over 90 min, 5-Fluoruracil continuous infusion of 2400 mg/m2 IV over 46h.
  Other Names:

  • 5-FU
  • leucovorin
  • oxaliplatin
• Drug: Gemcitabine / Nab-paclitaxel
  Both drugs are administered once weekly for three weeks (days 1, 8, 15) followed by a week of rest (28-day cycle) for 3 cycles prior to imaging. Gemcitabine: 1000 mg/m2 intravenous infusion over 30 to 40 minutes. Nab-paclitaxel: 125 mg/m2 intravenous infusion over 30 to 40 minutes.
  Other Name: gemcitabine / abraxane
• Radiation: Stereotactic body radiation therapy
  The radiation dose will be limited to 30 Gy maximum for the small bowel. For other organs, we will follow the "as low as reasonably achievable" principle. Radiation quality assurance will be performed for all treatment plans. Volumes of tumour obtained on CT images at 1.25 mm slice thickness will be reconstructed into a three-dimensional image set for SBRT planning. The SBRT will deliver a radiation dose of 36 Gy in three fractions with 12 Gy per fraction to the isodose line best encompassing the planning target volume, including a 2 mm expansion around the gross tumour.
  Other Name: SBRT

Study Arms

Single Arm Intervention

1. Chemotherapy: 6 cycles (three months) of IV combination chemotherapy with mFOLFIRINOX on day 1 followed by one week of rest (14-day cycle). Alternatively, patients will receive three months of gemcitabine / nab-paclitaxel.
2. Re-staging CT scan with Carbohydrate Antigen (CA) 19-9 serum test.
3. Radiation therapy with SBRT for 5 days.
4. Re-staging CT scan with CA 19-9 serum test one week following the last day of SBRT . Staging laparoscopy to rule out occult metastatic disease is optional based on surgeon's preference.
5. Pancreatectomy 4 weeks following the last day of SBRT as per standard of care.
6. Adjuvant chemotherapy: as per standard of care.
7. Clinical assessment and CT scan with CA 19-9 serum test at 4-month intervals until identification of cancer recurrence.
8. Follow up of patients after 2 years every six months for up to 5 years following the initiation of treatment will be performed off-protocol as per standard of care.

Interventions:

• Drug: mFOLFIRINOX
• Drug: Gemcitabine / Nab-paclitaxel
• Radiation: Stereotactic body radiation therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: June 29, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 1, 2026
• Estimated Primary Completion Date: May 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 1. Men and women 18 years of age or older who present with biopsy proven borderline resectable pancreatic adenocarcinoma who are medically fit for surgery as per assessment by treating surgeon.

  2. Age ≤ 79 years 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 4. Normal bone marrow and organ function

  1. Absolute neutrophil count (ANC) = or > 1500, platelets > 100K
  2. Total bilirubin <1.5x upper limit of normal (ULN)
  3. Alanine transaminase (ALT), Aspartate aminotransferase (AST) < 3 x ULN
  4. Creatinine <150umol/L
  5. Normal prothrombin time and international normalized ratio (INR) 5. Able to provide written informed consent

Exclusion Criteria:

1. Proven metastatic disease (e.g. on imaging modality such as CT scan of the chest, abdomen and pelvis or MRI)
2. Locally advanced pancreatic cancer (see definition section 3.3)
3. Prior treatment with radiation therapy to the pancreas or associated field.
4. Contraindications to receive chemotherapy
5. History of cardiac disease including congestive heart failure (New York Heart Association class 2), active coronary artery disease or uncontrolled hypertension
6. Concurrent ongoing systemic infections
7. Illegal substance abuse, or social conditions that may interfere with patient's participation in the trial
8. Pre-existing neuropathy
9. Pregnant patients

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pablo E Serrano, MD; 905-521-2100 ext 43872; serrano@mcmaster.ca

Contact: Leyo Ruo, MD; 905-521-2100; ruol@mcmaster.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT04452461
• Other Study ID Numbers: 5076
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Pablo Serrano, Hamilton Health Sciences Corporation
• Study Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pablo E Serrano, MD; McMaster University

• PRS Account: Hamilton Health Sciences Corporation
• Verification Date: June 2020