GTX-RT in Borderline Resectable Pancreatic Cancer

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01754623
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 19.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if a program of intensive chemotherapy with gemcitabine, docetaxel and capecitabine followed by an advanced form of focused radiation aimed at participant's tumor followed by more chemotherapy can increase the chances that the participant's pancreatic tumor can be removed completely.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: Capecitabine; Drug: Gemcitabine; Drug: Docetaxel; Radiation: Stereotactic body radiation therapy (SBRT); Other: Restaging review after radiation; Procedure: Surgery; Drug: 5-Fluorouracil	Phase 2

Detailed Description

Investigators plan to conduct a prospective pilot phase II trial of GTX-SBRT as neoadjuvant treatment of borderline resectable pancreatic cancer. After informed consent, pretreatment pancreatic tumor tissues will be collected and immediately frozen at the time of staging endoscopic ultrasound (EUS). Ribonucleic acid (RNA) will be extracted from tumor specimens and run on microarray analysis to determine radiosensitivity index score. Borderline resectable (BR) patients will be treated with 3 cycles of GTX chemotherapy followed by SBRT. They will be restaged and evaluated for resectability 3 to 4 weeks later. Non-metastatic patients who are deemed resectable after neoadjuvant therapy will be taken to surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Validation of a Radiation Response Signature in Borderline Resectable Pancreatic Cancer Patients Treated With Induction Chemotherapy Followed by Stereotactic Body Radiation Therapy (SBRT)
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Chemotherapy Followed by Radiation Treatment Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.

Drug: Capecitabine; Treatment will begin with the first round of chemotherapy. Each round of chemotherapy will take 21 days. Each round or cycle will start with participants taking capecitabine pills. Participants will take tablets of capecitabine (Xeloda®) twice per day for 14 days followed by 7 days without capecitabine.; Other Names: Xeloda® ; Drug: Gemcitabine; On the fourth day of the cycle, participants will be treated with gemcitabine and docetaxel. First, this will consist of placing gemcitabine (Gemzar®) in a bag of fluid and giving it by vein over 30 minutes.; Other Names: Gemzar® ; Drug: Docetaxel; On the fourth day of the cycle, participants will be treated with gemcitabine and docetaxel. After the gemcitabine, participants will receive docetaxel (Taxotere®) in a bag of fluid over 1 hour.; Other Names: Taxotere® ; Radiation: Stereotactic body radiation therapy (SBRT); 30/40 Gy to pancreatic tumor/area of borderline resectability; Other Names: SBRT ; Other: Restaging review after radiation; After radiation, participants will be re-evaluated for surgery. Patients who have Complete Response (CR), Partial Response (PR) or stable disease (SD) will proceed with surgical exploration and resection provided they are suitable fit for surgery in the judgment of the surgical oncologist. Patients who have local progression on imaging scan will be offered conventional 5-Fluorouracil based intensity-modulated radiation therapy (IMRT). If no surgery: then chemotherapy. If surgery: chemotherapy will be given based on response.; Procedure: Surgery; Non-metastatic patients who are deemed resectable after neoadjuvant therapy will be taken to surgery. After surgery, chemotherapy will be given based on response.; Drug: 5-Fluorouracil; Patients who have local progression on imaging scan will be offered conventional 5-Fluorouracil based intensity-modulated radiation therapy (IMRT).

Outcome Measures

Primary Outcome Measures

1. Margin-negative (R0) Resection Rate [Up to 3 years]

   R0 rate for all participants with resection. Margin negative surgery (R0 resection) is an absolute part of the curative treatment of pancreatic cancer.The primary endpoint is correlation of a radio sensitivity index score derived from the microarray analysis and pathologic response on surgical specimens. Tumor regression Rating: R0 (Complete Response). R0 resections are scored as those resections in which the common bile duct margin, pancreatic resection margin, retroperitoneal margin are negative for tumor involvement.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) at Three Years [3 years]

   PFS is defined as the duration of time from enrollment to time of death or progression of disease, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the longest diameter (LD) of the target lesion or appearance of new lesions at metastatic sites.

2. Overall Survival (OS) Rate [12 months]

   OS at time of analysis, calculated from date of enrollment to date of death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that is borderline resectable disease. Borderline resectable lesions are defined as:

• circumferential tumor abutment with the superior mesenteric vein (SMV) or portal vein (PV) or SMV/PV confluence over </= 180°

• circumferential tumor abutment with the superior mesenteric artery (SMA) over </= 180°

• Short segment encasement (360°) of the PV or SMV that is amenable to partial vein resection and reconstruction

• encasement of the gastroduodenal artery up to the origin of the hepatic artery

• Patients must have measurable disease

• No previous chemotherapy or radiation to the pancreas

• Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%)

• Patients must have normal organ and marrow function as defined below:

• leukocytes >/= 3,000/μL

• absolute neutrophil count >/= 1,000/ μL

• platelets >/= 100,000/ μL

• creatinine within normal institutional limits (ULN)

• total bilirubin will allow for 2x the upper limit of the institution. Patients may have biliary stents or drains to lower total bilirubin to this range.

• Has a negative serum or urine pregnancy test within 7 days prior to initiation of therapy (female patients of childbearing potential). Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Patients will agree to continue contraception for 30 days from the date of the last study drug administration.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients with metastatic disease are ineligible.

• Patients who have had prior chemotherapy for pancreatic adenocarcinoma

• Patients who have received prior radiation to an abdominal site are not eligible.

• Patients with peripheral neuropathy >/= grade 2

• Patients with a history of severe hypersensitivity reaction to Taxotere (docetaxel), other drugs formulated with polysorbate 80, gemcitabine, or capecitabine

• Patients may not be receiving any other investigational agents.

• ECOG Performance Status 3-4

• Pregnant or breast-feeding women are excluded from this study because gemcitabine,capecitabine, and docetaxel are Class D agents with the potential for teratogenic or abortifacient effects.

• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients must not have any comorbid inflammatory conditions of the bowel such as Crohn's Disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Ravi Shridhar, M.D., Ph.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01754623
• Other Study ID Numbers: MCC-16932
• First Posted: Dec 21, 2012
• Last Update Posted: Aug 13, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: Pancreas; Pancreatic; Neoplasms; Stereotactic; Radiosurgery; Borderline; Resectable; Gastrointestinal; Gemcitabine; Capecitabine; Fluorouracil; Docetaxel; SBRT; GTX Chemotherapy
• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Fluorouracil; Capecitabine; Docetaxel

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at Moffitt Cancer Center from March 2013 through December 2013.

Arm/Group Title	Chemotherapy Followed by Radiation Treatment
Arm/Group Description	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chemotherapy Followed by Radiation Treatment
Arm/Group Description	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 22.2%
>=65 years	7 77.8%
Sex: Female, Male (Count of Participants)
Female	5 55.6%
Male	4 44.4%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Margin-negative (R0) Resection Rate
Description	R0 rate for all participants with resection. Margin negative surgery (R0 resection) is an absolute part of the curative treatment of pancreatic cancer.The primary endpoint is correlation of a radio sensitivity index score derived from the microarray analysis and pathologic response on surgical specimens. Tumor regression Rating: R0 (Complete Response). R0 resections are scored as those resections in which the common bile duct margin, pancreatic resection margin, retroperitoneal margin are negative for tumor involvement.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All participants with resection

Arm/Group Title	Chemotherapy Followed by Radiation Treatment
Arm/Group Description	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.
Measure Participants	3
Number [percentage of participants]	67 744.4%

2. Secondary Outcome

Title	Progression-Free Survival (PFS) at Three Years
Description	PFS is defined as the duration of time from enrollment to time of death or progression of disease, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the longest diameter (LD) of the target lesion or appearance of new lesions at metastatic sites.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Evaluable participants at 3 years.

Arm/Group Title	Chemotherapy Followed by Radiation Treatment
Arm/Group Description	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival (OS) Rate
Description	OS at time of analysis, calculated from date of enrollment to date of death from any cause.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All participants per group

Arm/Group Title	All Participants -Chemotherapy Followed by Radiation Treatment	Resection Group -Chemotherapy Followed by Radiation Treatment
Arm/Group Description	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.
Measure Participants	9	3
Number [percentage of participants]	33 366.7%	100 NaN

Adverse Events

Time Frame	1 year, 5 months
Arm/Group Title	Chemotherapy Followed by Radiation Treatment
Arm/Group Description	Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.
All Cause Mortality
	Chemotherapy Followed by Radiation Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Chemotherapy Followed by Radiation Treatment
	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)
Gastrointestinal disorders
Abdominal pain	1/9 (11.1%)	1
Diarrhea	2/9 (22.2%)	2
Mucositis oral	1/9 (11.1%)	1
Hepatobiliary disorders
Bile duct stenosis	1/9 (11.1%)	1
Hepatobiliary disorders - Other, Liver abscess	1/9 (11.1%)	1
Infections and infestations
Biliary tract infection	1/9 (11.1%)	1
Urinary tract infection	1/9 (11.1%)	1
Investigations
Alanine aminotransferase increased	1/9 (11.1%)	1
Aspartate aminotransferase increased	1/9 (11.1%)	1
Blood bilirubin increased	1/9 (11.1%)	1
Neutrophil count decreased	1/9 (11.1%)	1
Metabolism and nutrition disorders
Dehydration	2/9 (22.2%)	2
Hyponatremia	1/9 (11.1%)	1
Renal and urinary disorders
Acute kidney injury	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/9 (11.1%)	1
Vascular disorders
Hypotension	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Chemotherapy Followed by Radiation Treatment
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Anemia	6/9 (66.7%)	14
Gastrointestinal disorders
Diarhea	6/9 (66.7%)	9
Constipation	5/9 (55.6%)	6
Abdmonimal pain	2/9 (22.2%)	4
Mucositis oral	2/9 (22.2%)	3
Vomiting	2/9 (22.2%)	2
Abdominal distension	1/9 (11.1%)	1
Bloating	1/9 (11.1%)	1
Dyspepsia	1/9 (11.1%)	1
Nausea	1/9 (11.1%)	2
General disorders
Fatigue	9/9 (100%)	13
Fever	2/9 (22.2%)	2
Flu like symptoms	2/9 (22.2%)	2
Chills	1/9 (11.1%)	1
Edema limbs	1/9 (11.1%)	2
Irritability	1/9 (11.1%)	1
Infections and infestations
Lip infection	1/9 (11.1%)	1
Lung infection	1/9 (11.1%)	1
Sepsis	1/9 (11.1%)	1
Urinary tract infection	1/9 (11.1%)	1
Investigations
Neutrophil count decreased	3/9 (33.3%)	5
Platelet count decreased	3/9 (33.3%)	8
Aspartate aminotransferase increased	1/9 (11.1%)	2
Weight loss	2/9 (22.2%)	2
White blood cell decreased	2/9 (22.2%)	5
Blood bilirubin increased	1/9 (11.1%)	2
CD4 lymphocytes decreased	1/9 (11.1%)	4
Lipase increased	1/9 (11.1%)	1
Lymphocyte count decreased	1/9 (11.1%)	1
Pancreatic enzymes	1/9 (11.1%)	1
Metabolism and nutrition disorders
Anorexia	4/9 (44.4%)	5
Dehydration	3/9 (33.3%)	4
Hyperglycemia	4/9 (44.4%)	7
Hypoalbuminemia	3/9 (33.3%)	8
Hypokalemia	3/9 (33.3%)	3
Hyponatremia	2/9 (22.2%)	4
Hypocalcemia	1/9 (11.1%)	2
Hypomagnesemia	1/9 (11.1%)	1
Hypophosphatemia	1/9 (11.1%)	2
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/9 (11.1%)	1
Nervous system disorders
Dizziness	2/9 (22.2%)	2
Dysgeusia	1/9 (11.1%)	1
Headache	1/9 (11.1%)	1
Psychiatric disorders
Confusion	2/9 (22.2%)	2
Depressioin	2/9 (22.2%)	2
Insomnia	2/9 (22.2%)	2
Hallucinations	1/9 (11.1%)	1
Restlessness	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/9 (11.1%)	1
Epistaxis	1/9 (11.1%)	1
Hiccups	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	3/9 (33.3%)	6
Alopecia	2/9 (22.2%)	3
Palmar-plantar erthrodysesthesia syndrome	2/9 (22.2%)	3
Pruritus	2/9 (22.2%)	2
Rash acneiform	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders - Other, Tegaderm skin reaction from IV	1/9 (11.1%)	1
Vascular disorders
Superficial thrombophlebitis	3/9 (33.3%)	4
Hypertension	2/9 (22.2%)	2
Hypotension	2/9 (22.2%)	2
Hematoma	1/9 (11.1%)	1

Limitations/Caveats

The study only accrued 9 (of planned 35) participants. It was not possible to collect adequate pre-treatment tissue for radiosensitivity index (RSI) analysis, pre-treatment. The study was terminated before planned completion.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.