Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer
NCT ID: NCT02311361
Last Updated: 2021-04-20
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE1/PHASE2
Total Enrollment
65 participants
Study Classification
INTERVENTIONAL
Study Start Date
2015-03-25
Study Completion Date
2020-12-31
Brief Summary
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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.
\- 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.
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Detailed Description
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Background:
Tremelimumab is a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Anti-CTLA4 therapy has been shown to enhance anti-tumor immunity by blocking tumor-induced immune suppression of cytotoxic T cells.
Durvalumab is a human monoclonal antibody directed against Programmed death-ligand 1 (PD-L1). Blockage of ligation between PD-L1 and Programmed cell death protein 1 (PD1) induces local immune activation and prevent anergy and exhaustion of effectors T-cells.
Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation.
The underlying hypothesis of this study is that the effect of Immune Checkpoint inhibitor (Durvalumab with or without Tremelimumab) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma.
Objective:
To determine the safety, tolerability and feasibility of immune checkpoint inhibition \[comprising either Durvalumab alone, or combined Durvalumab and Tremelimumab\] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer.
Eligibility:
Histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) with at least 1 measurable metastatic lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and accessible for biopsy. There is no limit to the number of prior chemotherapy regimens received.
Patients must be greater than or equal to 18 years of age and have a performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 1
Life expectancy of greater than 3 months.
Acceptable organ and bone marrow function.
Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.
No active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment.
No active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. No active or history of systemic lupus erythematosus, Wegeners granulomatosis.
Design:
Subjects will be assigned to 4 arms
Anti-PDL1 (Durvalumab) in combination with radiation (8 Gray (Gy) in fraction)
\- Anti-PDL1 (Durvalumab) in combination with radiation (5 Gy in 5 fractions)
Anti-PDL1 (Durvalumab) and anti-CTLA4 (Tremelimumab) in combination with radiation (8 Gy in 1 fractions)
\- Anti-PDL1 (Durvalumab) and anti-CTLA4 (Tremelimumab) in combination with radiation (5 Gy in 5 fractions).
Tremelimumab is a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Anti-CTLA4 therapy has been shown to enhance anti-tumor immunity by blocking tumor-induced immune suppression of cytotoxic T cells.
Durvalumab is a human monoclonal antibody directed against Programmed death-ligand 1 (PD-L1). Blockage of ligation between PD-L1 and Programmed cell death protein 1 (PD1) induces local immune activation and prevent anergy and exhaustion of effectors T-cells.
Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation.
The underlying hypothesis of this study is that the effect of Immune Checkpoint inhibitor (Durvalumab with or without Tremelimumab) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma.
Objective:
To determine the safety, tolerability and feasibility of immune checkpoint inhibition \[comprising either Durvalumab alone, or combined Durvalumab and Tremelimumab\] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer.
Eligibility:
Histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) with at least 1 measurable metastatic lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and accessible for biopsy. There is no limit to the number of prior chemotherapy regimens received.
Patients must be greater than or equal to 18 years of age and have a performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 1
Life expectancy of greater than 3 months.
Acceptable organ and bone marrow function.
Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.
No active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment.
No active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. No active or history of systemic lupus erythematosus, Wegeners granulomatosis.
Design:
Subjects will be assigned to 4 arms
Anti-PDL1 (Durvalumab) in combination with radiation (8 Gray (Gy) in fraction)
\- Anti-PDL1 (Durvalumab) in combination with radiation (5 Gy in 5 fractions)
Anti-PDL1 (Durvalumab) and anti-CTLA4 (Tremelimumab) in combination with radiation (8 Gy in 1 fractions)
\- Anti-PDL1 (Durvalumab) and anti-CTLA4 (Tremelimumab) in combination with radiation (5 Gy in 5 fractions).
Conditions
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Pancreatic Neoplasms
Pancreatic Cancer
Cancer of Pancreas
Cancer of the Pancreas
Pancreas Cancer
Study Design
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Allocation Method
NON_RANDOMIZED
Intervention Model
SEQUENTIAL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Durvalumab + 8 Gray (Gy) in 1 fraction
Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction
Group Type
EXPERIMENTAL
Durvalumab
Intervention Type
BIOLOGICAL
10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Sterostatic body radiation therapy (SBRT)
Intervention Type
RADIATION
8 Gray (Gy) x 1; 5Gy x 5
Durvalumab +5 Gy in 5 fractions
Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions
Group Type
EXPERIMENTAL
Durvalumab
Intervention Type
BIOLOGICAL
10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Sterostatic body radiation therapy (SBRT)
Intervention Type
RADIATION
8 Gray (Gy) x 1; 5Gy x 5
Tremelimumab + 8 Gy in 1 fraction
Cohort 3/Dose Level B1 (was removed with Amendment A) Tremelimumab + 8 Gy in 1 fraction
Group Type
EXPERIMENTAL
Tremelimumab
Intervention Type
BIOLOGICAL
75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT)
Intervention Type
RADIATION
8 Gray (Gy) x 1; 5Gy x 5
Tremelimumab + 5 Gy in 5 fractions
Cohort 4/Dose Level B2 (was removed with Amendment A) Tremelimumab + 5 Gy in 5 fractions
Group Type
EXPERIMENTAL
Tremelimumab
Intervention Type
BIOLOGICAL
75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT)
Intervention Type
RADIATION
8 Gray (Gy) x 1; 5Gy x 5
Durvalumab +Tremelimumab + 8 Gy in 1 fraction
Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction
Group Type
EXPERIMENTAL
Durvalumab
Intervention Type
BIOLOGICAL
10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Tremelimumab
Intervention Type
BIOLOGICAL
75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT)
Intervention Type
RADIATION
8 Gray (Gy) x 1; 5Gy x 5
Durvalumab +Tremelimumab +5 Gy in 5 fractions
Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions
Group Type
EXPERIMENTAL
Durvalumab
Intervention Type
BIOLOGICAL
10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Tremelimumab
Intervention Type
BIOLOGICAL
75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT)
Intervention Type
RADIATION
8 Gray (Gy) x 1; 5Gy x 5
Interventions
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Durvalumab
10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Intervention Type
BIOLOGICAL
Tremelimumab
75 mg IV, every 4 weeks for 16 weeks
Intervention Type
BIOLOGICAL
Sterostatic body radiation therapy (SBRT)
8 Gray (Gy) x 1; 5Gy x 5
Intervention Type
RADIATION
Other Intervention Names
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MEDI4736
Ticilmumab
Sterostatic ablative radiotherapy
Eligibility Criteria
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Inclusion Criteria
* Patients must have histopathological confirmation of pancreatic adenocarcinoma prior to entering this study by the Laboratory of Pathology of the National Cancer Institute (NCI) to entering this study by the Laboratory of Pathology of the NCI prior to entering this study
* Patients must have disease that is not amenable to potentially curative resection. Primary in-situ (or locally-recurrent) tumor must be present and, in the opinion of radiation oncology, be amenable to radiation therapy as planned in the protocol. Each case will be discussed at GI tumor board with multidisciplinary team.
* Patients must have at least 1 measurable metastatic lesion by Response Evaluation in Solid Tumors (RECIST) 1.1 criteria.
* There is no limit to the number of prior chemotherapy regimens received. Patients must have received at least one line of prior systemic chemotherapy for advanced unresectable and/or metastatic disease.
* Age greater than or equal to 18 years
* Life expectancy of greater than 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patients must have normal organ and marrow function as defined below:
* absolute neutrophil count - \> 1,000/mcL
* Platelets - greater than or equal to 100,000/mcL
* total bilirubin - Bili should be less than or equal to 2 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin less than 3.0 mg/dL)
* serum albumin - greater than or equal 2.5 g/dL
Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransaminase (AST) up to 3 x ULN. (up to 5 x ULN if liver metastases present)
--Creatinine - \< 2X institution upper limit of normal
OR
--creatinine clearance - \>45 mL/min/1.73 m(2), for patients with creatinine levels above institutional normal
* Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.
* Patient must be able to understand and willing to sign a written informed consent document.
* Patients must have disease that is not amenable to potentially curative resection. Primary in-situ (or locally-recurrent) tumor must be present and, in the opinion of radiation oncology, be amenable to radiation therapy as planned in the protocol. Each case will be discussed at GI tumor board with multidisciplinary team.
* Patients must have at least 1 measurable metastatic lesion by Response Evaluation in Solid Tumors (RECIST) 1.1 criteria.
* There is no limit to the number of prior chemotherapy regimens received. Patients must have received at least one line of prior systemic chemotherapy for advanced unresectable and/or metastatic disease.
* Age greater than or equal to 18 years
* Life expectancy of greater than 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patients must have normal organ and marrow function as defined below:
* absolute neutrophil count - \> 1,000/mcL
* Platelets - greater than or equal to 100,000/mcL
* total bilirubin - Bili should be less than or equal to 2 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin less than 3.0 mg/dL)
* serum albumin - greater than or equal 2.5 g/dL
Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransaminase (AST) up to 3 x ULN. (up to 5 x ULN if liver metastases present)
--Creatinine - \< 2X institution upper limit of normal
OR
--creatinine clearance - \>45 mL/min/1.73 m(2), for patients with creatinine levels above institutional normal
* Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.
* Patient must be able to understand and willing to sign a written informed consent document.
Exclusion Criteria
* Malignant ascites that is clinically detectable by physical examination or is symptomatic. Evidence of radiographic ascites that is not clinically significant will not be an exclusion criterion.
* Any prior Grade greater than or equal to 3 imAE while receiving immunotherapy, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment, or any unresolved imAE \> Grade 1. Note: Active or history of vitiligo will not be a basis for exclusion.
* Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. Note: Local surgeries for isolated lesions for palliative intent are acceptable. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.
* Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Durvalumab (MEDI4736) or tremelimumab, or compromise the ability of the subject to give written informed consent.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
* Subjects with vitiligo or alopecia
* Requirement for intermittent use of bronchodilators or local steroid injections
* Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment
* History of primary immunodeficiency or history of active tuberculosis. Note: Latent tuberculosis will not be a basis for exclusion.
* Diverticulitis (either active or history of) within the past 2 years. Note that diverticulosis is permitted.
* Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol.
* True positive test results for hepatitis A (Immunoglobulin M (IgM) positive). Subjects with a history of hepatitis A with Immunoglobulin G (IgG) blood test are not excluded. True positive test results hepatitis B, or C infection.
* Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegeners granulomatosis.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 and tremelimumab. The following are exceptions to this criterion:
* Intranasal, inhaled, and topical steroids
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication)
* History of sarcoidosis syndrome.
* Patients should not be vaccinated with live attenuated vaccines within 1 month of starting Tremelimumab and MEDI4736 treatment. Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of both drugs.
* Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and Tremelimumab or MEDI4736. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that Tremelimumab or MEDI4736 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events.
* History of hypersensitivity reaction to human or mouse antibody products.
* Pregnancy and breast feeding are exclusion factors. The effects of Tremelimumab and MEDI4736 on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 180 days (female patients) or 90 days (male patients) after the end of the treatment. In addition male patients must refrain from sperm donation for 90 days after the final dose of investigational product. Female patients must refrain from egg cell donation for 180 days after the final dose of investigational product. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
* Any prior Grade greater than or equal to 3 imAE while receiving immunotherapy, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment, or any unresolved imAE \> Grade 1. Note: Active or history of vitiligo will not be a basis for exclusion.
* Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. Note: Local surgeries for isolated lesions for palliative intent are acceptable. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.
* Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Durvalumab (MEDI4736) or tremelimumab, or compromise the ability of the subject to give written informed consent.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
* Subjects with vitiligo or alopecia
* Requirement for intermittent use of bronchodilators or local steroid injections
* Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment
* History of primary immunodeficiency or history of active tuberculosis. Note: Latent tuberculosis will not be a basis for exclusion.
* Diverticulitis (either active or history of) within the past 2 years. Note that diverticulosis is permitted.
* Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol.
* True positive test results for hepatitis A (Immunoglobulin M (IgM) positive). Subjects with a history of hepatitis A with Immunoglobulin G (IgG) blood test are not excluded. True positive test results hepatitis B, or C infection.
* Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegeners granulomatosis.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 and tremelimumab. The following are exceptions to this criterion:
* Intranasal, inhaled, and topical steroids
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
* Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication)
* History of sarcoidosis syndrome.
* Patients should not be vaccinated with live attenuated vaccines within 1 month of starting Tremelimumab and MEDI4736 treatment. Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of both drugs.
* Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and Tremelimumab or MEDI4736. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that Tremelimumab or MEDI4736 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events.
* History of hypersensitivity reaction to human or mouse antibody products.
* Pregnancy and breast feeding are exclusion factors. The effects of Tremelimumab and MEDI4736 on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 180 days (female patients) or 90 days (male patients) after the end of the treatment. In addition male patients must refrain from sperm donation for 90 days after the final dose of investigational product. Female patients must refrain from egg cell donation for 180 days after the final dose of investigational product. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
Minimum Eligible Age
18 Years
Maximum Eligible Age
99 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Cancer Institute (NCI)
NIH
Sponsor Role
lead
Responsible Party
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Tim Greten, M.D.
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Tim F Greten, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)
Locations
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Site Status
Countries
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United States
References
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Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.
Reference Type
BACKGROUND
Reyes-Gibby CC, Chan W, Abbruzzese JL, Xiong HQ, Ho L, Evans DB, Varadhachary G, Bhat S, Wolff RA, Crane C. Patterns of self-reported symptoms in pancreatic cancer patients receiving chemoradiation. J Pain Symptom Manage. 2007 Sep;34(3):244-52. doi: 10.1016/j.jpainsymman.2006.11.007. Epub 2007 May 21.
Reference Type
BACKGROUND
Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr, Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969 Oct 25;2(7626):865-7. doi: 10.1016/s0140-6736(69)92326-5. No abstract available.
Reference Type
BACKGROUND
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form: Arms A1 and A2 Consent
Document Type: Informed Consent Form: Arms C1 and C2 Consent
Related Links
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https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2015-C-0027.html
NIH Clinical Center Detailed Web Page
Other Identifiers
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15-C-0027
Identifier Type: -
Identifier Source: secondary_id
150027
Identifier Type: -
Identifier Source: org_study_id
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ACTIVE_NOT_RECRUITING
PHASE2
Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma
NCT01146054
COMPLETED
PHASE2
Immune Checkpoint Inhibition in Combination With Radiation Therapy in Pancreatic Cancer or Biliary Tract Cancer Patients
NCT02866383
COMPLETED
PHASE2
Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy
NCT05927142
RECRUITING
PHASE1/PHASE2
Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer
NCT03816358
ACTIVE_NOT_RECRUITING
PHASE1
A Study of Durvalumab in Patients With BR PDA Following Neoadjuvant Therapy and Successful Surgical Resection
NCT03038477
WITHDRAWN
PHASE2
Role of Cyberknife Stereotactic Radiation Therapy (SBRT) Followed by Gemcitabine for Patients With Locally Advanced Pancreatic Cancer
NCT01304160
COMPLETED
PHASE1/PHASE2
Combination Chemotherapy and Radiation Therapy Plus Surgery in Treating Patients With Advanced Cancer of the Pancreas
NCT00020345
COMPLETED
PHASE2
Study With CY, Pembrolizumab, GVAX Pancreas Vaccine, and SBRT in Patients With Locally Advanced Pancreatic Cancer
NCT02648282
COMPLETED
PHASE2
Chemoradiation and Radiosurgery Boost in Treating Patients With Locally Advance Pancreatic Cancer That May or May Not be Removed by Surgery
NCT01739439
TERMINATED
PHASE1
Durvalumab Plus "Booster" RT for Metastatic Adenocarcinoma Pancreas Cancer Post Chemotherapy (GCC 1598)
NCT02885727
WITHDRAWN
PHASE2
Combination Chemotherapy and Radiation Therapy in Treating Patients With Pancreatic Cancer
NCT00026130
COMPLETED
PHASE2
Gemcitabine, Herceptin and Radiation to Treat Cancer of the Pancreas
NCT00005926
COMPLETED
PHASE2
A Pilot Study to Evaluate Radiotherapy-Induced Anti-Tumor Immunity in Metastatic Carcinoma of the Pancreas
NCT01985958
COMPLETED
NA
Chemotherapy, Stereotactic Body Radiation Therapy & Nelfinavir Mesylate in Locally Advanced Pancreatic Cancer
NCT01959672
COMPLETED
PHASE2
Gemcitabine With or Without Radiation Therapy in Treating Patients With Pancreatic Cancer
NCT00057876
COMPLETED
PHASE3
Phase II Study of MEDI4736 Monotherapy or in Combinations With Tremelimumab in Metastatic Pancreatic Ductal Carcinoma
NCT02558894
COMPLETED
PHASE2
Immunotherapy and SBRT Study in Borderline Resectable Pancreatic Cancer
NCT02405585
TERMINATED
PHASE2
Safety and Immunological Effect of Pembrolizumab in Resectable or Borderline Resectable Pancreatic Cancer
NCT02305186
UNKNOWN
PHASE1/PHASE2