Pancreatic Cancer, Periampullary Adenocarcinoma
Conditions
Keywords
recurrent, unresectable, residual, stereotactic body radiation therapy (SBRT), palliative management
Brief summary
The investigators are looking to see if a certain dose of stereotactic body radiation therapy (SBRT) may be a viable treatment option for recurrent or residual pancreatic or periampullary adenocarcinoma.
Detailed description
No standard treatment option has yet been established for patients with recurrent or residual disease after definitive treatment of pancreatic or periampullary cancers (duodenal, ampullary, bile duct). Linac based stereotactic body radiation therapy (SBRT) administered in 1-3 fractions has been shown to be an effective treatment option for patients with unresectable, locally advanced pancreatic adenocarcinoma, achieving local control rates of 84-92% at one year. Associated late gastrointestinal toxicity rates have been reported to be 22-25% at 1 year. We hypothesize that similarly excellent local control rates (80-90% at one year) with a reasonable rate of toxicity (≤20%) can be achieved using Linac based SBRT delivered as 5 Gy x 5 for patients with local failure (remaining disease) after previous treatment with conventional chemoradiation therapy (CRT) with or without surgery and as 6.6 Gy x 5 for radiation-naïve patients with local failure (remaining disease) after previous treatment with surgery and/or chemotherapy. The toxicities of note for this trial are grade 2 and greater gastritis, fistula, enteritis, ulcer, or any other grade 3 or greater gastrointestinal toxicity.
Interventions
RADIATIONStereotactic Body Radiation Therapy (SBRT)
Stereotactic Body Radiation Therapy (SBRT) which included 5 consecutive fractions of 25 to 33 Gy, following 3 months of multiagent chemotherapy.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, non-randomized, controlled Phase 2 trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Karnofsky Performance Status greater than or equal to 70% * confirmed pancreatic or periampullary adenocarcinoma * pancreatic or periampullary tumor less than 8.0 cm in greatest axial dimension * Either: * standard of care treatment for pancreatic cancer that included radiation therapy \* patients may be receiving continued chemotherapy post initial CRT. or * standard of care treatment for pancreatic cancer that did not include radiation therapy \* patients must have attempted chemotherapy upon initial diagnosis * acceptable organ and marrow function as determined by blood tests * ability to understand and give consent * must be a patient to be treated with SBRT only at Johns Hopkins Hospital * life expectancy of greater than 3 months
Exclusion criteria
* extensive metastatic disease * performance status of less than 70 * children are excluded form the study * no uncontrolled intercurrent illness * no concurrent malignancy other than melanoma * pregnant or breast feeding women are excluded * women who are not post-menopausal and have a positive pregnancy test * life expectancy of less than 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Late Gastrointestinal Toxicities | 3 months post-treatment to date of first progression or date of death, whichever comes first assessed up to 36 months | Late (Up to 3 months post-treatment to date of first progression or date of death, (whichever comes first-up to 36 months) Grade 2 or greater gastritis, enteritis, fistula, or ulcer and any other grade 3 or greater gastrointestinal toxicity attributable to Stereotactic Body Radiation Therapy (SBRT). Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0) and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Progression Free Survival From SBRT | From date of randomization until the date of first documented progression or death from any cause (up to 36 months). | Local progression free survival defined as the length of time (months) during and after the treatment of a disease that a patient lives with cancer, but the disease does not worsen. |
| Local Progression Free Survival From Diagnosis | From date documented diagnosis to date of first documented local disease progression. | Local progression free survival defined as the length of time (months) during and after the treatment of a disease that a patient lives with cancer, but the disease does not worsen. |
| Toxicity for Patients With Chemotherapy and Radiation (no Resection) | Up to 36 months | Toxicity was assessed for grade ≥2 gastrointestinal toxic effects using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. |
| Change in Patient Reported Quality of Life (PR-QOL) Assessment at Baseline (Pre-treatment) and 3 Months (Post-Treatment) | Baseline (Pre-SBRT) and at 3 months (Post-SBRT) | To evaluate whether a change in patient reported quality of life (QoL) occurred between baseline (pre-SBRT) and at 3 months (post-SBRT) using the European Organization for Research and Treatment in Cancer quality of life core cancer questionnaire with the pancreatic cancer module (EORTC QLQ-C30/Pan26). This assessment is a multi-dimensional, 30-item questionnaire which assesses 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales ( fatigue, pain and nausea/vomiting), a global health/QoL scale as well as 6 single items. There are also 26 questions specific to patients with pancreatic cancer. Scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems. |
| Acute Gastrointestinal Toxicity | within 3 months of treatment | Any acute gastrointestinal (GI) toxicities grade 3 or greater. |
| Linac Based SBRT Standardization | 3, 6, and 12 months after treatment | To develop and standardize Linac based SBRT delivery and dosimetric parameters |
| FDG-PET Use for Planning and Estimation of Survival | 3, 6, and 12 months after treatment and then annually thereafter | To evaluate the utility of FDG-PET for treatment planning and estimation of progression-free survival. |
| Toxicity for Patients With Chemotherapy, Surgery (Resection) and Radiation for Tumor Assessments | Up to 36 months | Toxicity was assessed for grade ≥2 gastrointestinal toxic effects using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. |
| Linear Accelerator (Linac) Based SBRT Pain Control | 3, 6, and 12 months after treatment | To evaluate the ability of Linac based SBRT to provide pain control among symptomatic patients as measured by pain medication requirement at 3, 6 and 12 months after treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma Patients with pathologically confirmed, locally advanced pancreatic ductal adenocarcinoma (LAPC), unresectable at diagnosis, or local recurrence pancreatic ductal adenocarcinoma (PDAC) after prior surgical resection. | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 33 Participants | — |
| Age, Categorical Between 18 and 65 years | 15 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 31 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 45 / 48 |
| other Total, other adverse events | 3 / 48 |
| serious Total, serious adverse events | 10 / 48 |
Outcome results
Primary
Late Gastrointestinal Toxicities
Late (Up to 3 months post-treatment to date of first progression or date of death, (whichever comes first-up to 36 months) Grade 2 or greater gastritis, enteritis, fistula, or ulcer and any other grade 3 or greater gastrointestinal toxicity attributable to Stereotactic Body Radiation Therapy (SBRT). Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0) and the Radiation Therapy Oncology Group radiation morbidity scoring criteria.
Time frame: 3 months post-treatment to date of first progression or date of death, whichever comes first assessed up to 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Late Gastrointestinal Toxicities | 13 Participants |
Secondary
Acute Gastrointestinal Toxicity
Any acute gastrointestinal (GI) toxicities grade 3 or greater.
Time frame: within 3 months of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Acute Gastrointestinal Toxicity | 3 Participants |
Secondary
Change in Patient Reported Quality of Life (PR-QOL) Assessment at Baseline (Pre-treatment) and 3 Months (Post-Treatment)
To evaluate whether a change in patient reported quality of life (QoL) occurred between baseline (pre-SBRT) and at 3 months (post-SBRT) using the European Organization for Research and Treatment in Cancer quality of life core cancer questionnaire with the pancreatic cancer module (EORTC QLQ-C30/Pan26). This assessment is a multi-dimensional, 30-item questionnaire which assesses 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales ( fatigue, pain and nausea/vomiting), a global health/QoL scale as well as 6 single items. There are also 26 questions specific to patients with pancreatic cancer. Scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.
Time frame: Baseline (Pre-SBRT) and at 3 months (Post-SBRT)
Population: Not all patients completed the QOL assessments. In this case 43 of the 48 patients completed assessments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Change in Patient Reported Quality of Life (PR-QOL) Assessment at Baseline (Pre-treatment) and 3 Months (Post-Treatment) | 0 score on a scale |
Secondary
FDG-PET Use for Planning and Estimation of Survival
To evaluate the utility of FDG-PET for treatment planning and estimation of progression-free survival.
Time frame: 3, 6, and 12 months after treatment and then annually thereafter
Population: We prioritized collecting and analyzing data for the primary outcome of this study which is reported in ClinicalTrials.gov. Unfortunately, due to lack of funding, we were not able to collect and analyze all secondary outcome data as planned.
Secondary
Linac Based SBRT Standardization
To develop and standardize Linac based SBRT delivery and dosimetric parameters
Time frame: 3, 6, and 12 months after treatment
Population: We prioritized collecting and analyzing data for the primary outcome of this study which is reported in ClinicalTrials.gov. Unfortunately, due to lack of funding, we were not able to collect and analyze all secondary outcome data as planned. Therefore, dosimetric parameters were not developed
Secondary
Linear Accelerator (Linac) Based SBRT Pain Control
To evaluate the ability of Linac based SBRT to provide pain control among symptomatic patients as measured by pain medication requirement at 3, 6 and 12 months after treatment.
Time frame: 3, 6, and 12 months after treatment
Population: We prioritized collecting and analyzing data for the primary outcome of this study which is reported in ClinicalTrials.gov. Unfortunately, due to lack of funding, we were not able to collect and analyze all secondary outcome data as planned.
Secondary
Local Progression Free Survival From Diagnosis
Local progression free survival defined as the length of time (months) during and after the treatment of a disease that a patient lives with cancer, but the disease does not worsen.
Time frame: From date documented diagnosis to date of first documented local disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Local Progression Free Survival From Diagnosis | 21.6 Months until local progression |
Secondary
Local Progression Free Survival From SBRT
Local progression free survival defined as the length of time (months) during and after the treatment of a disease that a patient lives with cancer, but the disease does not worsen.
Time frame: From date of randomization until the date of first documented progression or death from any cause (up to 36 months).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Local Progression Free Survival From SBRT | 14.6 Months until local progression |
Secondary
Toxicity for Patients With Chemotherapy and Radiation (no Resection)
Toxicity was assessed for grade ≥2 gastrointestinal toxic effects using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and the Radiation Therapy Oncology Group radiation morbidity scoring criteria.
Time frame: Up to 36 months
Population: Participants who had chemotherapy and radiation (no resection)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Toxicity for Patients With Chemotherapy and Radiation (no Resection) | 7 Participants |
Secondary
Toxicity for Patients With Chemotherapy, Surgery (Resection) and Radiation for Tumor Assessments
Toxicity was assessed for grade ≥2 gastrointestinal toxic effects using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and the Radiation Therapy Oncology Group radiation morbidity scoring criteria.
Time frame: Up to 36 months
Population: Participants who had chemotherapy, surgery (resection) and radiation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Locally Advanced Pancreatic Cancer or Locally Recurrent Pancreatic Ductal Adenocarcinoma | Toxicity for Patients With Chemotherapy, Surgery (Resection) and Radiation for Tumor Assessments | 6 Participants |