Clinical trial NCT02599662: Intraoperative Radiation Therapy for Resectable Pancreas Cancer
Official title: Phase I Study of Low Kilovoltage Intraoperative Radiation for Patients With Resectable Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Pancreas Cancer
Keywords: Cancer
Intraoperative Radiation Therapy - IORT
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2015-11-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Currently, for patients with pancreatic cancer the standard treatment is surgery followed by chemotherapy and/or radiation therapy. An investigational approach is to perform the surgery and treat the area of the tumor with intraoperative radiotherapy in one procedure. Intraoperative radiation delivers low energy x-rays to a targeted area during the time of tumor removal.

The purpose of this study is to learn about both the good and bad effects of adding intraoperative radiation therapy. Another goal is to determine and compare the quality of life before and after the procedure. We will also monitor the effect of the therapy on the cancer lesion and any complications that may result.

Detailed description: The purpose of this study is to determine safety of low kilovoltage radiotherapy delivery of a focused dose of radiation to the areas at high risk for locoregional recurrence following pancreaticoduodenectomy. This surgery is currently the only potentially curative approach for patients with pancreatic cancer. Unfortunately, following surgery alone \>50% of patients will have a local recurrence of disease \[5\]. Local control will become increasingly important as chemotherapy regimens continue to improve the distant metastases-free survival. Intraoperative radiation therapy allows direct access to the tumor bed and areas of concern while allowing displacement and shielding of normal tissue and organs at risk of radiation toxicity.

Study Objectives The primary objective is to determine the maximum tolerated dose (MTD) for low kilovoltage (kV) intraoperative radiotherapy (IORT)

The secondary objectives are:

To develop acute and chronic toxicity profiles for this treatment modality

To determine the feasibility of including low-kV IORT in the treatment of pancreatic cancer

To evaluate the following physics and delivery parameters: treatment prescription dose, depth of treatment, applicator type, and treatment time.

To measure patient's quality of life (QOL) before and after treatment, including change in pain level and fatigue level.

To describe the disease specific outcomes of local regional control, progression free-survival, distant metastasis free-survival, disease free-survival and overall survival associated with low-kV IORT following pancreaticoduodenectomy.

Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed pancreatic adenocarcinoma.
* Age ≥ 18 years.
* Performance status ECOG 0-1.
* Patient must have resectable disease. In order to be resectable the following criteria must be met:
* Absence of distant metastases.
* Clear fat planes around the celiac axis, hepatic artery, and superior mesenteric artery .
* Absence of direct involvement of inferior vena cava or aorta.
* Stage I and stage II disease per AJCC 7th edition.
* Complete history and physical examination including weight and ECOG performance status within 31 days of entry.
* Laboratory data obtained ≤ 14 days prior to registration on study, with adequate bone marrow and organ function defined as follows:

Laboratory Test Result Leukocytes ≥3000/mm3 Absolute Neutrophil Count (ANC) ≥1500/mm3 Platelets ≥100,000/mm3 Total Bilirubin ≤1.4 mg/dL AST(SGOT),ALT(SPGT) ≤2.5 x institutional upper limit of normal Serum creatinine ≤1.4 mg/dL INR ≤1.5 BUN \< 20 mg/dL Albumin ≥3.5 g/dL

* Negative serum pregnancy test for females of childbearing potential within 14 days of study registration. Should a female participant become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone tubal ligation, or remaining celibate by choice) who meets the following criteria:

  * Has not undergone a hysterectomy or bilateral oophorectomy; or
  * Has not been naturally postmenopausal for at least 12 consecutive months.
* Abdominal CT scan with contrast prior to performance of surgery. If patient is allergic to contrast an abdominal MRI may substitute. Other imaging may be added or substituted as deemed appropriate by the treatment team (surgeon, radiation oncologist, medical oncologist).
* Ability to understand and the willingness to sign a written informed consent.
* Signed study specific informed consent.
* Patients with prior history of malignancy are permitted to register in the study as long as they are not actively taking cytotoxic or biologic medication for treatment of the prior malignancy. Patient must be disease-free from any malignancy for at least the previous 6 months and must have no history of brain metastases.
* Consultation, agreement, and documentation by a radiation oncologist that the patient is suitable to receive radiotherapy per this protocol.
* Consultation, agreement, and documentation by surgeon that the patient is a suitable surgical candidate.
* Consultation, agreement, and documentation by an anesthesiologist that patient is suitable to receive general anesthesia.

Exclusion Criteria:

* Defined treatment area which cannot be adequately covered by the radiation field as defined by the radiation oncology treatment team.
* Patients who have received neoadjuvant chemotherapy are ineligible.
* Patients with Stage III-Stage IV disease.
* Patients who have been on an immunosuppressive agent (excluding corticosteroids) within 4 weeks of the proposed operation.
* Patients receiving any other investigational agents.
* Current pregnancy or currently nursing.
* History of brain metastases.
* Severe, active comorbidity defined as follows
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months. \[23\]
* Myocardial infarction within 3 months of study registration \[23\].
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
* Chronic Obstructive Pulmonary Disease or other respiratory illness hospitalization or precluding study therapy at time of registration \[23\].
* Uncontrolled diabetes which in the opinion of any of the patient's physicians requires an immediate change in management. A patient may be considered eligible if the patient's physician managing the diabetes deems the appropriate changes in management have resulted in adequate control. \[23\].
* BMI \>30.
* Patient with active diagnosis of a bleeding disorder. \[23\]
* Patients enrolled in another interventional clinical trial.

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 52 weeks
Secondary outcomes:
measure: QOL surveys
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
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