Durvalumab and "Booster" Radiation in Metastatic Adenocarcinoma of the Pancreas

NCT03490760 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: ESR 15 11078
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenocarcinoma of the Pancreas

Keywords

Metastatic Adenocarcinoma of the Pancreas

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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.

  1 year

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  1 year

• Clinical Benefit Rate (CBR)

  1 year

• Time to In-field Progression

  1 year

• Overall Survival (OS)

  1 year

Study Arms (1)

Durvalumab plus Radiation Therapy

EXPERIMENTAL

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.

Drug: Durvalumab; Radiation: Radiation Therapy

Interventions

Durvalumab DRUG

Durvalumab 1500 mg (or 20 mg/m2 if \<30 kg) IV every 4 weeks

Durvalumab plus Radiation Therapy

Radiation Therapy RADIATION

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.

Durvalumab plus Radiation Therapy

Eligibility Criteria

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

You may qualify if:

• 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 1.
• 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

You may not qualify if:

• 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.
• Any unresolved toxicity (\> grade 2, Common Terminology Criteria for Adverse Events version 4.03) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved immune-related adverse event (irAE) \>Grade 1.
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency.

Sponsors & Collaborators

• Baptist Health South Florida: lead
• AstraZeneca: collaborator

Study Sites (1)

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Related Links

• Miami Cancer Institute website

MeSH Terms

Interventions

durvalumab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

This study was terminated early because of poor enrollment and participants being withdrawn soon after enrollment due to disease progression. Statistical analysis was not possible with the small number of evaluable participants.

Results Point of Contact

• Title: Michael Chuong, M.D.
• Organization: Miami Cancer Institute at Baptist Health, Inc.

michaelchu@baptisthealth.net

(786) 596-2000

Study Officials

• Michael D. Chuong, MD

  Miami Cancer Institute at Baptist Health, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm Phase II

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: April 6, 2018
• Study Start: November 9, 2018
• Primary Completion: July 9, 2020
• Study Completion: July 9, 2020
• Last Updated: October 12, 2023
• Results First Posted: October 12, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)