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NCT02311361

Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer

Completed Phase 1, PHASE2 Results posted Last updated 20 April 2021
What this trial tests

Phase 1, PHASE2 trial testing Durvalumab in Pancreatic Neoplasms in 65 participants. Completed in 31 December 2020.

Timeline
25 March 2015
Primary endpoint
23 October 2019
31 December 2020

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment65
Start date25 March 2015
Primary completion23 October 2019
Estimated completion31 December 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Pancreatic Neoplasms or Pancreatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Primary · Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.

Adverse Events (AEs) are reported by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1=Mild, Grade 2= Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Fatal.

Grade 1 Abdominal pain
GroupValue95% CI
Cohort A Dose Level A10
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C21
Grade 1 Alanine aminotransferase increased
GroupValue95% CI
Cohort A Dose Level A11
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C25
Grade 1 Alkaline Phosphatase increased
GroupValue95% CI
Cohort A Dose Level A10
Cohort A Dose Level A22
Cohort C Dose Level C10
Cohort C Dose Level C22
Grade 1 Anemia
GroupValue95% CI
Cohort A Dose Level A13
Cohort A Dose Level A23
Cohort C Dose Level C19
Cohort C Dose Level C29
Grade 1 Anorexia
GroupValue95% CI
Cohort A Dose Level A11
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C23
Grade 1 Atrial fibrillation
GroupValue95% CI
Cohort A Dose Level A10
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C21
Grade 1 Aspartate aminotransferase increased
GroupValue95% CI
Cohort A Dose Level A11
Cohort A Dose Level A20
Cohort C Dose Level C11
Cohort C Dose Level C26
Grade 1 Back pain
GroupValue95% CI
Cohort A Dose Level A10
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C21
Percentage of Participants With 6-month Overall Survival Secondary · 6 month

Participants who survived at least 6 months after therapy.

GroupValue95% CI
Cohort A Dose Level A126
Cohort A Dose Level A258
Cohort C Dose Level C112
Cohort C Dose Level C240
Overall Survival Secondary · From study entry to death or date of last contact, whichever occurs first, up to 2 years of follow-up

Amount of time participants survived after therapy.

GroupValue95% CI
Cohort A Dose Level A13.31.2 – 6.6
Cohort A Dose Level A29.00.5 – 18.4
Cohort C Dose Level C12.11.1 – 4.3
Cohort C Dose Level C24.22.9 – 9.3
Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) Secondary · At screening then every 8 weeks until disease progression or patient is taken off the trial, whichever comes first, approximately 6 months.

Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

Complete Response
GroupValue95% CI
Cohort A Dose Level A10
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C20
Partial Response
GroupValue95% CI
Cohort A Dose Level A11
Cohort A Dose Level A20
Cohort C Dose Level C10
Cohort C Dose Level C21
Stable Disease
GroupValue95% CI
Cohort A Dose Level A13
Cohort A Dose Level A24
Cohort C Dose Level C12
Cohort C Dose Level C25
Progressive Disease
GroupValue95% CI
Cohort A Dose Level A14
Cohort A Dose Level A24
Cohort C Dose Level C16
Cohort C Dose Level C210
Progression Free Survival (PFS) Secondary · From study entry to disease progression, death or date of last contact, whichever occurs first, an average of 6 months

PFS is the defined as the median amount of time subject survives without disease progression after treatment. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:

GroupValue95% CI
Cohort A Dose Level A11.70.8 – 2.0
Cohort A Dose Level A22.50.1 – 3.7
Cohort C Dose Level C10.90.7 – 2.1
Cohort C Dose Level C22.31.9 – 3.4
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) Secondary · Date treatment consent signed to date off study, approximately 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one

GroupValue95% CI
Durvalumab + 8 Gray (Gy) in 1 Fraction14
Durvalumab +5 Gy in 5 Fractions10
Durvalumab +Tremelimumab + 8 Gy in 1 Fraction19
Durvalumab +Tremelimumab +5 Gy in 5 Fractions20

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose Level C2.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Durvalumab + 8 Gray (Gy) in 1 Fraction
Serious: 6/14 (43%)
Deaths: 14/14
Durvalumab +5 Gy in 5 Fractions
Serious: 2/11 (18%)
Deaths: 8/11
Durvalumab +Tremelimumab + 8 Gy in 1 Fraction
Serious: 11/19 (58%)
Deaths: 2/19
Durvalumab +Tremelimumab +5 Gy in 5 Fractions
Serious: 12/20 (60%)
Deaths: 3/20

Serious adverse events (46 terms)

ReactionSystemDurvalumab + 8 Gray (Gy) i…Durvalumab +5 Gy in 5 Frac…Durvalumab +Tremelimumab +…Durvalumab +Tremelimumab +…
DehydrationMetabolism and nutrition disorders
Death NOSGeneral disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, deathNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Blood bilirubin increasedInvestigations
NauseaGastrointestinal disorders
DiarrheaGastrointestinal disorders
HyponatremiaMetabolism and nutrition disorders
ColitisGastrointestinal disorders
FatigueGeneral disorders
HypoalbuminemiaMetabolism and nutrition disorders
MalaiseGeneral disorders
VomitingGastrointestinal disorders
DysphagiaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Small intestinal obstructionGastrointestinal disorders
Infections and infestations - Other, specifyInfections and infestations
AlkalosisMetabolism and nutrition disorders
AscitesGastrointestinal disorders
Cardiac disorders - Other, pulm embolismCardiac disorders
Chest pain - cardiacMusculoskeletal and connective tissue disorders
Duodenal obstructionGastrointestinal disorders
Gastrointestinal disorders - Other, Abdominal crampingGastrointestinal disorders
GastroparesisGastrointestinal disorders
HypertensionVascular disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (163 terms — click to expand)

ReactionSystemDurvalumab + 8 Gray (Gy) i…Durvalumab +5 Gy in 5 Frac…Durvalumab +Tremelimumab +…Durvalumab +Tremelimumab +…
Alkaline phosphatase increasedInvestigations
Lymphocyte count decreasedInvestigations
AnemiaBlood and lymphatic system disorders
HypoalbuminemiaMetabolism and nutrition disorders
FatigueGeneral disorders
Abdominal painGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
Alanine aminotransferase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
Platelet count decreasedInvestigations
Activated partial thromboplastin time prolongedInvestigations
AnorexiaInvestigations
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrheaGastrointestinal disorders
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
PainGeneral disorders
AscitesGastrointestinal disorders
VomitingGastrointestinal disorders
Weight lossInvestigations
Back painMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
DizzinessNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
White blood cell decreasedInvestigations
FeverGeneral disorders
HypercalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
BloatingGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Edema limbsGeneral disorders
HeadacheNervous system disorders
HyperuricemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
Skin and subcutaneous tissue disorders - Other, specifySkin and subcutaneous tissue disorders
ConfusionPsychiatric disorders

Most-reported serious reactions: Dehydration, Death NOS, Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, death, Blood bilirubin increased, Nausea, Diarrhea, Hyponatremia, Colitis.

Data from ClinicalTrials.gov NCT02311361 adverse events section.

Sponsor's own description

Background: \- Stereotactic body radiation therapy (SBRT) is used to treat cancer. It is a way of giving very focused beams of radiation to tumors. Researchers think that the drugs being used in this study might work better when combined with SBRT in people with pancreatic cancer. Objective: \- To study the safety and effectiveness of Durvalumab (MEDI4736) and/or tremelimumab with SBRT. Eligibility: \- People 18 and older who have pancreatic cancer that has not responded or to chemotherapy. They must be candidates for radiation but not resection. Design: * Participants will be screened with medical history and physical exam. They will have blood tests. Their tumor will be measured using computerized tomography (CT) or magnetic resonance imaging (MRI). * Participants will have their tumor biopsied with a needle. They will have also have a biopsy after cycle 1. * Participants will get 1 or 2 drugs in combination with the SBRT. * For MEDI4736, the duration of each cycle will be 28-days. Participants will get the drug through an intravenous (IV) infusion twice in each cycle (Days 1 and 15). * For tremelimumab, the duration of the first 6 cycles will each last 28 days. Then the duration of the last 3 cycles will change to 12 weeks. Participants will get the drug through an IV once in each cycle. * All participants will have SBRT. Some will get 1 dose of radiation and some will get 5. CT scans will map their tumor. * Participants will have medical history, physical exam, and blood tests in each cycle. They will have a CT scan or MRI every 8 weeks. Cycles will continue for up to 12 months. * Participants will be contacted yearly for follow-up.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Challenges and Opportunities for Pancreatic Cancer Immunotherapy.
    Bear AS, Vonderheide RH, O'Hara MH. · · 2020 · cited 500× · PMID 32946773 · DOI 10.1016/j.ccell.2020.08.004
  2. Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
    Naimi A, Mohammed RN, Raji A, Chupradit S, et al · · 2022 · cited 350× · PMID 35392976 · DOI 10.1186/s12964-022-00854-y
  3. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  4. Current clinical trials testing the combination of immunotherapy with radiotherapy.
    Kang J, Demaria S, Formenti S. · · 2016 · cited 293× · PMID 27660705 · DOI 10.1186/s40425-016-0156-7
  5. Current and future immunotherapeutic approaches in pancreatic cancer treatment.
    Farhangnia P, Khorramdelazad H, Nickho H, Delbandi AA. · · 2024 · cited 153× · PMID 38835055 · DOI 10.1186/s13045-024-01561-6
  6. Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options.
    Kabacaoglu D, Ciecielski KJ, Ruess DA, Algül H. · · 2018 · cited 152× · PMID 30158932 · DOI 10.3389/fimmu.2018.01878
  7. Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment.
    Looi CK, Chung FF, Leong CO, Wong SF, et al · · 2019 · cited 131× · PMID 30987642 · DOI 10.1186/s13046-019-1153-8
  8. Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors.
    Derer A, Frey B, Fietkau R, Gaipl US. · · 2016 · cited 118× · PMID 26590829 · DOI 10.1007/s00262-015-1771-8

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Other trials of Durvalumab

Trials testing the same drug.

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Currently open trials in the same condition.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02311361.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing