MR Guided Dose Escalated RT + Concurrent Chemotherapy in Unresectable Pancreatic Cancer

• Sponsor: Medical College of Wisconsin
• Information provided by (Responsible Party): Beth Erickson, Medical College of Wisconsin

Study Description

Brief Summary:

This research study is for people who have pancreas cancer for which surgery is not recommended. Potential patients must have already received several months of chemotherapy before they are eligible for this study and there will not have been any detectable spread of their tumor on imaging studies following this chemotherapy course.

Condition or disease	Intervention/treatment	Phase
Unresectable Pancreatic Cancer	Radiation: Radiation Therapy; Drug: Concurrent chemotherapy (Gemcitabine, Capecitabine)	Phase 2

Detailed Description:

In this study the investigators want to find out more about the efficacy of giving higher doses of radiation with concurrent chemotherapy in controlling unresectable pancreas cancers than are used in either the pre-operative or post-operative setting. The investigators will assess acute and late side effects (problems and symptoms) of radiation therapy given at these higher doses of radiation (dose escalated) following full dose chemotherapy given before the radiation and with concurrent chemotherapy for pancreas cancer. Radiation therapy is given in higher doses that are limited by the proximity of normal organs to the radiation dose distribution to improve the likelihood of controlling the tumor in the pancreas while minimizing the risk of radiation injury to these organs. There are two chemotherapy drugs, Capecitabine is an oral drug taken twice per day on the same day that radiation therapy is given and Gemcitabine is an intravenous drug given once per week, during radiation therapy. Everyone in this study will have already received chemotherapy alone first. Everyone in this study will receive radiation therapy and concurrent chemotherapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 23 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MR Guided Phase II Radiotherapy Dose Escalation in Unresectable Non-metastatic Pancreatic Cancer
• Study Start Date: March 2016
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Radiation therapy plus chemotherapy; MR guided dose escalated radiation therapy plus concurrent chemotherapy in unresectable non-metastatic pancreas cancer. Radiation therapy dose escalation to an MR-defined GTV of up to 69.75 Gy at 2.25 Gy per fraction and concurrent Gemcitabine or Capecitabine.

Radiation: Radiation Therapy; Radiation therapy dose escalation to an MR-defined GTV of up to 69.75 Gy at 2.25 Gy per fraction.; Other Name: Dose escalation radiation therapy; Drug: Concurrent chemotherapy (Gemcitabine, Capecitabine); Gemcitabine 400mg 1m2 IV weekly x 6 doses. Capecitabine 825 mg/mm2 po bid Monday-Friday on days of radiation use 500mg tablets.; Other Names: Gemcitabine; Capecitabine

Outcome Measures

Primary Outcome Measures :

1. To evaluate the efficacy of dose escalation to an MR-defined GTV of up to 69.75 Gy at 2.25 Gy per fraction for unresectable pancreatic cancer. [ Time Frame: One year from the start of treatment ]
   To evaluate acute and late (> 3 months post treatment) radiation induced toxicities.

Secondary Outcome Measures :

1. To evaluate radiographic and biochemical response for patients treated with the proposed dose escalation. [ Time Frame: One year from the start of treatment ]
   To evaluate radiographic and biochemical response for patients treated with the proposed dose escalation using pre- and post- treatment MR and PET scanning in addition to routine surveillance CT scans and CEA/ CA 19-9 levels.
2. Radiation induced toxicities [ Time Frame: > 3 months post treatment ]
   To evaluate acute (> 3 months post treatment) and late radiation induced toxicities.
3. SMAD 4 expression [ Time Frame: 4 years ]
   SMAD 4 expression vs pattern of relapse
4. Survival rates [ Time Frame: 7 years ]
   1 & 2 year overall survival, median survival and progression survival rates.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

3.1 Conditions for Patient Eligibility

• Pathologically confirmed (histologic or cytologic), locally advanced, adenocarcinoma of the pancreas; patients must have unresectable disease based on institutional standardized criteria of unresectability or medical inoperability.
• Patients with and without regional adenopathy are eligible.
• No distant metastases, based upon the following minimum diagnostic workup:
• History/physical examination, including collection of weight and vital signs, within 28 days prior to study entry;
• Abdominal/pelvic CT scan with IV contrast within 21 days prior to study entry;
• Chest CT scan, or X-ray within 21 days prior to study entry. Abdominal/pelvic MR prior to radiation with perfusion and diffusion- weighted sequences and MR and CT sim for radiation planning Pet scan within 21 days prior to study entry, Functional renal study.
• Zubrod performance status 0-1 within 1 week of study entry.
• Age ≥ 18.
• Heme Onc and CA 19-9/CEA within 14 days prior to study entry, as follows.
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
• Platelets ≥ 100,000 cells/mm3;
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);
• Serum creatinine ≤ 1.5 mg/dl;
• ALT or AST < 3 x upper limit of normal;
• Total bilirubin < 3.0 mg/dL;
• Alkaline phosphatase < 3 x upper limit of normal;
• Fasting blood glucose < 160 mg/dl.
• Negative serum pregnancy test (if applicable) within 14 days prior to study entry.
• Ability to swallow oral medications.
• Patients must have had at least 4 months of prior systemic chemotherapy.
• Patient must provide study specific informed consent prior to study entry.
• Women of childbearing potential and male participants who are sexually active must practice adequate contraception.

Exclusion criteria:

Distant metastatic disease, second malignancy or peritoneal seeding;

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).

Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.

Any major surgery within 28 days prior to study entry

Severe, active co-morbidity, defined as follows:

Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;

Transmural myocardial infarction within 3 months prior to study entry;

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;

Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function;

Any unresolved bowel or bile duct obstruction;

Major resection of the stomach or small bowel that could affect the absorption of capecitabine

Acquired immune deficiency syndrome (AIDS) based upon current CDC definition;

Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during the course of the study and for women, for 3 months after the last study drug administration.

Women who are lactating at the time of registration and who plan to be lactating through 3 months after the last study drug administration.

Prior allergic reaction to capecitabine or gemcitabine

Inability to undergo an MR of the abdomen/pelvis

Participation in another clinical treatment trial while on study.

Contacts and Locations

Contacts

Contact: Cancer Center Clinical Trials Office; 1-800-680-0505 ext 8900; cccto@mcw.edu

Locations

United States, Wisconsin

Froedtert Hospital; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Beth Erickson, MD 414-805-4460 berickson@mcw.edu

Contact 1-866-680-0505 ext 8900 cccto@mcw.edu

Principal Investigator: Beth Erickson, MD

Sponsors and Collaborators

Medical College of Wisconsin

Investigators

• Principal Investigator: Beth Erickson, MD; Froedtert & The Medical College of Wisconsin

More Information

• Responsible Party: Beth Erickson, Professor, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT01972919 History of Changes
• Other Study ID Numbers: 17687
• First Posted: October 31, 2013
• Last Update Posted: November 12, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Capecitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs