Phase I Study of Stereotactic Body Radiation Therapy and FOLFIRINOX in the Neoadjuvant Therapy of Pancreatic Cancer
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Purpose
The purpose of this study is to determine whether using FOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) prior to surgery in patients with pancreatic cancer is safe and well tolerated. This study will obtain preliminary data on the response of the cancer to this therapy by Magnetic Resonance Imaging (MRI) and by studying the cancer after it is resected surgically.
In addition, the investigators will perform biochemical studies on the tumor tissue obtained from your tissue biopsy as well as from the tumor removed by the surgeon in order to measure the effect of treatment with FOLFIRINOX and SBRT on several proteins that may be important in the behavior of pancreatic cancer cells.
The data obtained from this trial will be extremely valuable to help improve the approach to treating pancreatic cancer in the future. If you do not undergo surgery after completion of FOLFIRINOX + SBRT, the investigators will request a second biopsy of the tumor under computer tomography (CT) -guidance in order to measure the effect of treatment on your tumor.
| Condition | Intervention | Phase |
|---|---|---|
|
Cancer of Pancreas Cancer of the Pancreas Neoplasms, Pancreatic Pancreas Cancer Pancreas Neoplasms |
Drug: Modified FOLFIRINOX Radiation: Stereotactic Body Radiotherapy (SBRT) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study of Stereotactic Body Radiation Therapy and 5-Fluorouracil, Oxaliplatin and Irinotecan (FOLFIRINOX) in the Neoadjuvant Therapy of Pancreatic Cancer |
- Maximum tolerated total dose of stereotactic body radiation to patients with resectable or borderline resectable pancreas cancer following Folfirinox chemotherapy [ Time Frame: Four weeks ] [ Designated as safety issue: Yes ]
A standard 3 + 3 design will be used for evaluating the safety and tolerability of SBRT radiation doses. Any grade 3 liver, gastric, small bowel or spinal cord toxicity or any grade 4 toxicity (hematologic or other non-hematologic except for diarrhea) will be considered a dose limiting toxicity (DLT).
Each cohort will consist of 3 patients, unless 1 of the patients experiences a DLT in which case the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will be defined as the dose level below that which results in a DLT in 2 or more of the 6 patients in a cohort.
- Clinical and pathologic objective response rate as measured by MRI (clinical response) and histopathology and rate of complete resection (R0) (pathologic response) [ Time Frame: ten weeks ] [ Designated as safety issue: No ]
The overall pathologic (complete + partial) response rate and margin negative resection rate will be estimated two ways: using all registered, and resected patients (via the ITT principle, for effectiveness assessment).
The overall objective clinical response rate will involve MRI assessment of pancreas tumors of all registered patients with comparison of baseline MRI measurement to post-Folfirinox/post-SBRT measurement prior to surgical resection using RECIST criteria. Measurements will involve all registered patients.
| Estimated Enrollment: | 24 |
| Study Start Date: | November 2011 |
| Estimated Study Completion Date: | November 2014 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Oxaliplatin, Irinotecan and 5-Flurouracil infusion
Treatment cycles will be repeated every 15 days. The patients will receive up to 4 cycles of chemotherapy. The first cycle is given on week 1. The second cycle is given on week 3. The third cycle is given on week 5. The fourth cycle is given on week 7. Patients will be evaluated by history and physical, laboratory evaluation once weekly, including the week off of chemotherapy.
|
Drug: Modified FOLFIRINOX
Patients receive modified FOLFIRINOX Chemotherapy for 4 cycles (1 cycle = 15 days). Modified FOLFIRINOX: Oxaliplatin 85 mg/m2 intravenous infusion on day 1; Irinotecan 180 mg/m2 intravenous infusion on day 1; 5-Fluorouracil 2400 mg/m2 continuous intravenous infusion on days 1 to 3; pegylated filgrastim (neulasta) 6 mg subcutaneous injection on day 3.
Radiation: Stereotactic Body Radiotherapy (SBRT)
Stereotactic Body Radiotherapy: Begins 2 weeks after completion of final cycle of Folfirinox chemotherapy. Initial Dose Level 1 cohort: 10 Gy SBRT to primary tumor volume (PTV) and 2 Gy SBRT to retroperitoneal margin on days 1, 2, and 3. Total Gy to Gross tumor volume (GTV) is 36 Gy. Toxicity Assessment will occur weekly for 4 weeks.
Other Name: SBRT
|
Detailed Description:
The current standard of care for treating early stage pancreatic cancer involves surgery followed by chemotherapy and chemoradiotherapy using conventional fractionated external beam radiation therapy (EBRT). Despite the use of this standard treatment, the outcome for patients whose pancreatic cancers have been surgically removed remains poor. Patients with more advanced pancreatic cancers may experience even more inferior outcomes due to the difficulty to resect the cancer completely. In this particular group of patients, chemotherapy and radiation are offered to improve the resectability of the cancer.
Traditional chemotherapy used in the treatment of pancreatic cancer has included drugs such as gemcitabine. Recently, a chemotherapy regimen called Folfirinox has been used in the treatment of advanced pancreatic cancer. Fofirinox is also associated with improved outcomes when compared to gemcitabine in this particular group of patients.
Stereotactic body radiotherapy (SBRT) uses a higher dose of radiation to the cancer, but the treatment lasts for a significantly shorter period of time compared to conventional radiation. SBRT has advantages over conventional radiation that include: shorter duration of therapy (one to three days versus two to five weeks) and the ability to deliver full doses of chemotherapy. Studies evaluating SBRT for patients with pancreatic cancer have shown that SBRT is as effective as conventional radiation with less toxicity. SBRT combined with chemotherapy has been very well tolerated in patients with pancreatic cancer.
This study will ask whether giving chemotherapy with Folfirinox followed in short sequence by radiation therapy using a modified type of radiation, called Stereotactic Body Radiation Therapy (SBRT), is a feasible and safe approach. Also the investigators would like to see if this approach can improve the outcomes of patients who may undergo surgery for their pancreatic cancer.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must have histologic or cytologic diagnosis of pancreatic adenocarcinoma with radiological resectable or borderline resectable disease as determined by an experienced surgical oncologist at Emory.
- Patients must be 21 years or older.
- Patients must not have received prior chemotherapy or radiation for pancreatic cancer.
- Patients must have performance status of 0-1 on the ECOG (Eastern Oncology Group) scale (Appendix II).
- Patients must have adequate bone marrow function: absolute neutrophil count >1,500/cmm, platelet count >100,000/cmm.
- Patients must be informed of the investigational nature of this study and must give written informed consent prior to the receiving of treatment per this protocol.
Exclusion Criteria
- Patients with endocrine tumors or lymphoma of the pancreas.
- Patients whose tumor is less than 3 mm from the duodenum as measured by either CT or MRI
- History of central nervous system (CNS) metastases.
- Liver dysfunction, bilirubin > 1.5 mg/dL; aspartate transaminase (AST) and alanine amino transferase (ALT) > 5 times upper limit of institutional normal.
- Creatinine ≥ 1.5 mg/dL
- Albumin < 2.5 g/dL.
- INR ≥ 1.5 (in the absence of ongoing treatment with warfarin).
- Breast feeding.
- Serious active infection.
- Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).
- Active second primary malignancy (except in situ carcinoma of the cervix, or adequately treated basal cell carcinoma of the skin) within less than one year of enrollment into this study.
Contacts and Locations| Contact: Natalyn Hawk, MD | 1-888-946-7447 | nhawk@emory.edu |
| United States, Georgia | |
| Natalyn Hawk, MD | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Natalyn Hawk, MD | |
| Principal Investigator: | Natalyn Hawk, MD | Emory University Winship Cancer Institute |
More Information
No publications provided
| Responsible Party: | Natalyn N. Hawk, Principal Investigator, Emory University |
| ClinicalTrials.gov Identifier: | NCT01446458 History of Changes |
| Other Study ID Numbers: | WCI1998-11 |
| Study First Received: | September 26, 2011 |
| Last Updated: | June 17, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Emory University:
|
Cancer of Pancreas Cancer of the Pancreas Neoplasms, Pancreatic |
Pancreas Cancer Pancreas Neoplasms Entry Term Pancreatic Cancer |
Additional relevant MeSH terms:
|
Neoplasms Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Fluorouracil Oxaliplatin Irinotecan Antimetabolites Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Radiation-Sensitizing Agents Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013