Durvalumab Plus "Booster" RT for Metastatic Adenocarcinoma Pancreas Cancer Post Chemotherapy (GCC 1598)

NCT02885727 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HP-00070528
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Research Hypothesis: The combination of ionizing radiation and immunotherapy (durvalumab) is well tolerated and stimulates a clinically significant pancreas-cancer specific immune response. The primary objective will be to evaluate whether the combination of RT and durvalumab can improve median PFS compared to chemotherapy historical control data in metastatic pancreas cancer patients who have progressed through first-line chemotherapy. The primary intent of RT in this study is to augment a pancreatic cancer-specific immune response when given with durvalumab.

Conditions

Metastatic Pancreas Cancer

Outcome Measures

Primary Outcomes (1)

• Improvement in median Progression Free Survival using the combination of RT and durvalumab.

  The primary objective will be to evaluate whether the combination of RT and durvalumab improves median PFS compared to historical control in metastatic pancreas cancer patients who have progressed through first-line chemotherapy. PFS is defined as the time from the date of durvalumab initiation to the date of pancreatic cancer progression or death, whichever occurs first. This is a clinically relevant and appropriate endpoint for a phase II trial and since there are no prior studies using immune checkpoint blockade with concurrent RT for metastatic pancreatic cancer will allow for historical comparison to PFS using second-line chemotherapy.

  6 years

Study Arms (1)

Durvalumab + Radiation therapy

EXPERIMENTAL

Durvalumab (MEDI4736) 750 mg (or 10mg/kg if the patient weighs \<30 kg) IV Q2W over 1 hour for all patients + Radiation therapy * First lesion to receive 25 Gy / 5 daily consecutive fractions of 5 Gy * Second lesion to receive15 Gy / 5 daily consecutive fractions

Drug: Durvalumab; Radiation: Radiation Therapy

Interventions

Durvalumab DRUG

Evaluate if the combination of RT and durvalumab can improve median PFS compared to chemotherapy historical control data in metastatic pancreas cancer patients who have progressed through first-line chemotherapy

Also known as: (MEDI4736)

Durvalumab + Radiation therapy

Radiation Therapy RADIATION

The primary intent of RT in this study is to augment a pancreatic cancer-specific immune response when given with durvalumab.

Durvalumab + Radiation therapy

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥12 weeks as estimated by the investigator.
• Biopsy-proven metastatic pancreatic adenocarcinoma with progression through standard first-line chemotherapy. Chemotherapy given as part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy.
• ≥2 radiographically distinct and measurable pancreatic cancer lesions (primary and/or metastatic lesions) by RECIST 1.1 criteria separated by ≥5 cm
• No lesion that would receive RT \>7 cm in greatest dimension.
• Subjects must consent to all study procedures described in the protocol including radiographic evaluation and repeated blood draws.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrollment in the present study
• Any previous treatment with a PD1 or PD-L1 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 second-line or later chemotherapy for metastatic pancreatic cancer (prior chemotherapy received in the non-metastatic setting does not count).
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• 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, CTCAE 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 irAE \>Grade 1

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

durvalumab; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Shahed N Badiyan, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: August 31, 2016
• Study Start: July 1, 2017
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: September 12, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share