Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer

NCT00889187 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 08-375
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to determine if it is possible to deliver high dose radiation in one week while also giving the drug capecitabine for the treatment of pancreatic cancer prior to surgery, to determine if this treatment can be given safely for the treatment of pancreatic cancer prior to surgery and, to determine if this treatment can improve the local control pancreatic cancer prior to surgery compared to historical controls of standard treatment.

Conditions

Pancreatic Cancer

Keywords

radiation therapy; capecitabine

Outcome Measures

Primary Outcomes (3)

• Neoadjuvant Short-Course Photon Radiation Therapy Maximum Tolerated Dose (MTD) [Phase I]

  Neoadjuvant short-course photon radiation therapy MTD in combination with capecitabine 825 mg/m2 orally BID for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If none of 3 initial patients or only 1 of 6 patients have a DLT on dose level 3 then 6 additional patients are treated at this dose. If during this expansion, the rate of DLT exceeds 30% then the next lower dose level is declared the MTD. If no DLTs are observed, the MTD is not reached.

  within 3 weeks of the start of chemoradiation therapy

• Dose Limiting Toxicity (DLT) [Phase I]

  DLT occurring within 3 weeks of the start of chemoradiation therapy was defined as: Grade 3 non-hematologic or hematologic toxicity requiring interruption of \>7 days (d) of chemo or \>3d chemoradiation; Grade 4 non-hematologic; Grade 4 neutropenia or thrombocytopenia; Treatment-related death; Delays in surgery \>3 weeks due to treatment-related toxicity. A 30% increase in any surgical complication rate beyond those previously established rates (readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%, major intra-abdominal bleeding requiring return to OR: 1.6%, delayed gastric emptying: 4.4%, and superficial wound infection rate: 8%) was also considered a DLT.

  within 3 weeks of the start of chemoradiation therapy

• Grade 3-5 Toxicity Rate [Phase II]

  All Grade 3-5 events based on CTCAEv3 related to the accelerated dose (attribution possible, probable, definite) as reported on case report forms.

  within 3 weeks of the start of chemoradiation therapy

Secondary Outcomes (5)

• Local Recurrence Rate [Phase II]

  Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.

• Pathologic Response Rate [Phase II]

  Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy

• Progression-Free Survival (PFS) [Phase II]

  Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.

• Surgical Morbidity Rate [Phase II]

  Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy

• Surgical Mortality Rate [Phase II]

  Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy

Study Arms (5)

Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine

EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation: At dose level 1, a total dose of 30 Gy in 10 fractions (3 Gy/day) was prescribed to the 95% isodose and administered 5 days per week over 12 days. Chemotherapy: Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy. Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Radiation: Neoadjuvant Short-Course Photon Radiation; Drug: Capecitabine

Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine

EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation: At dose level 2, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 11 days. Chemotherapy: Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy. Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Radiation: Neoadjuvant Short-Course Photon Radiation; Drug: Capecitabine

Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine

EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation: At dose level 3, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 5 days. Chemotherapy: Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy. Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Radiation: Neoadjuvant Short-Course Photon Radiation; Drug: Capecitabine

All Phase I: Photon Rad+Capecitabine

EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation: All Phase I participants received the radiation regimen according to the established dose escalation schedule. Chemotherapy: Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy. Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Radiation: Neoadjuvant Short-Course Photon Radiation; Drug: Capecitabine

Phase II: Photon Rad (MTD)+Capecitabine

EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation: Phase II participants received the radiation regimen established in the Phase I study (MTD). Chemotherapy: Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy. Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Radiation: Neoadjuvant Short-Course Photon Radiation; Drug: Capecitabine

Interventions

Neoadjuvant Short-Course Photon Radiation RADIATION

All Phase I: Photon Rad+Capecitabine; Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine; Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine; Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine; Phase II: Photon Rad (MTD)+Capecitabine

Capecitabine DRUG

Also known as: Xeloda

All Phase I: Photon Rad+Capecitabine; Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine; Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine; Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine; Phase II: Photon Rad (MTD)+Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to treatment.
• No evidence of metastatic disease as determined by chest CT scan, abdominal CT scan (or MRI with gadolinium and/or manganese), and all patients must be staged with a physical exam, chest CT, and abdominal CT with intravenous contrast.
• Only potentially resectable patients are eligible. Potentially resectable is defined as: a)no extrapancreatic disease, b)no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery, and c)no evidence (on CT or MRI) of occlusion of the superior mesenteric vein or superior mesenteric-portal venous confluence.
• years of age or older
• ECOG Performance status of 0 or 1
• Women of child bearing potential must practice adequate contraception and to refrain from breast feeding. Female patients must have a negative pregnancy test within 7 days of treatment
• Lab values as specified in the protocol

You may not qualify if:

• Patients cannot have hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation
• Serious concomitant systemic disorders incompatible with the study, such as significant cardiac or pulmonary morbidity, or ongoing infection as manifested by fever
• Pregnant or lactating women
• Life expectancy \< 3 months
• Serious, uncontrolled, concurrent infection(s)
• Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor
• Treatment for other cancers within the last five years, except cured non-melanoma skin cancer and treated in situ cervical cancer
• Clinically significant cardiac disease or myocardial infarction within the last 12 months
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• Known, existing uncontrolled coagulopathy
• Unwillingness to participate or inability to comply with the protocol for the duration of the study
• Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier)
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Related Publications (1)

• Wo JY, Mamon HJ, Ferrone CR, Ryan DP, Blaszkowsky LS, Kwak EL, Tseng YD, Napolitano BN, Ancukiewicz M, Swanson RS, Lillemoe KD, Fernandez-del Castillo C, Hong TS. Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer. Radiother Oncol. 2014 Jan;110(1):160-4. doi: 10.1016/j.radonc.2013.10.027. Epub 2013 Nov 11.

  PMID: 24231241 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study did not proceed to phase II due to unexpected intraoperative complications experienced by patients enrolled on phase I.

Results Point of Contact

• Title: Harvey Mamon, MD, PhD
• Organization: Brigham and Women's Hospital / Dana Farber Cancer Institute

HMAMON@LROC.HARVARD.EDU

617-732-8564

Study Officials

• Harvey Mamon, MD, PhD

  Dana-Farber/Brigham and Women's Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 27, 2009
• First Posted: April 28, 2009
• Study Start: December 1, 2009
• Primary Completion: December 30, 2011
• Study Completion: December 30, 2011
• Last Updated: May 11, 2018
• Results First Posted: July 14, 2017

Record last verified: 2018-04

Locations

US (3)