Phase II Trial of In Situ Tumor Vaccination Using Durvalumab and "Booster" Radiation Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas Who Have Progressed Through First-line Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Adenocarcinoma of the Pancreas
- Sponsor
- Baptist Health South Florida
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Progression Free Survival
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a single-institution, single-arm phase II trial of Durvalumab combined with Radiation Therapy (RT) for metastatic pancreatic cancer patients who have progressed through first-line chemotherapy.
Detailed Description
This is a single-institution phase II trial of Durvalumab combined with Radiation Therapy (RT) for metastatic pancreatic cancer patients who have progressed through first-line chemotherapy. Pancreatic cancer patients who have received second-line or greater chemotherapy in the metastatic setting are not eligible. Target accrual is 39 patients. Durvalumab 1500 mg (or 20 mg/m2 if \<30 kg) IV every 4 weeks will be started and continued during RT and afterwards until the patient experiences either unacceptable toxicity or disease progression, whichever comes first. Patients must have at least three radiographically measurable pancreatic cancer lesions in different organs that have not previously received RT, two of which will receive RT. Eligible lesions include either the primary pancreatic tumor in unresected patients or distant metastatic lesions. Three fractions of 8 Gy each will be prescribed to one lesion during Week 3. Three fractions of 8 Gy each will be prescribed to the second lesion during Week 5. This is a single-arm trial with continuous monitoring of acute non-hematologic toxicity with the primary endpoint of progression free survival. Efficacy will be evaluated by time to progression or death, whichever comes first, and compared to historical control of chemotherapy alone as reported in the literature.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Biopsy-proven metastatic pancreatic adenocarcinoma with progression through standard first-line chemotherapy. Chemotherapy given as part of prior chemoradiation does not count as a line of therapy. Chemotherapy given as part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy.
- •At least 3 radiographically distinct pancreatic cancer lesions that are measurable by RECIST 1.1 criteria, including 2 that are eligible for RT.
- •Lesions that will receive RT are separated by ≥3 cm and none \>7 cm in greatest dimension.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of ≥12 weeks.
- •Adequate liver and kidney function.
- •Adequate blood cell count.
- •Female subjects must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry.
- •Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study
- •Previous enrollment in the present study.
- •Any previous treatment with a programmed cell death 1 or programmed cell death ligand 1 inhibitor including Durvalumab.
- •Prior RT to any lesion that would receive RT on this protocol.
- •Prior RT that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator.
- •Subjects who have received more than 1 line of chemotherapy in the metastatic setting.
- •History of another primary malignancy except for: 1) malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence; 2) adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; 3) adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ).
- •Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤14 days prior to the first dose of study drug.
- •Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of Durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
Arms & Interventions
Durvalumab plus Radiation Therapy
Durvalumab 1500 mg (or 20 mg/m2 if \<30 kg) IV every 4 weeks plus 24 Gy in 3 daily fractions to one lesion during Week 3 and 24 Gy in 3 daily fractions to the second lesion during Week 5.
Intervention: Durvalumab
Durvalumab plus Radiation Therapy
Durvalumab 1500 mg (or 20 mg/m2 if \<30 kg) IV every 4 weeks plus 24 Gy in 3 daily fractions to one lesion during Week 3 and 24 Gy in 3 daily fractions to the second lesion during Week 5.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: 1 year
Time from initiation of durvalumab to progression per RECIST 1.1 or death, whichever comes first. Per RECIST 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions compared to baseline sum of target lesions, or any new lesions. Confirmation of PD for participants who are deemed clinically stable by the Investigator should be acquired preferably at the next regularly scheduled imaging visit and no earlier than 4 weeks after the prior assessment of PD.
Secondary Outcomes
- Overall Survival (OS)(1 year)
- Overall Response Rate (ORR)(1 year)
- Time to In-field Progression(1 year)
- Clinical Benefit Rate (CBR)(1 year)