Neuroendocrine TumorsPhase 2DUNENCT03095274
Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin
A Phase 2 study testing Durvalumab and Tremelimumab in people with Neuroendocrine Tumors and Neuroendocrine Neoplasm of Lung, run by Grupo Espanol de Tumores Neuroendocrinos at 19 sites in Spain.
Trial summary
Well-differentiated gastroenteropancreatic and lung neuroendocrine tumors are generally malignancies with a prolonged natural history. However, clinical behavior is heterogeneous and when tumor progression is observed, treatment options are limited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Neuroendocrine Neoplasm of Lung
- What is being tested?
- Durvalumab and Tremelimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 19 sitesSpain
- Study dates
- 11 Apr 2017to 23 May 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained from the subject prior to performing any protocol-related procedures.
- Age >18 years at time of study entry.
- Subjects must have histologically confirmed diagnosis of one of the following advanced/metastatic neuroendocrine tumor types:
- Cohort 1: Well-moderately differentiated neuroendocrine tumors of the lung ( mitotic count ≤10 mitoses x 10 HPF), also known as typical and atypical lung carcinoids, that have progressed to prior somatostatin analog therapy and/or one prior targeted therapy or chemotherapy (only one prior systemic therapy, with the exception of patients that have been treated with somatostatin analogues and other systemic treatment, when two prior treatments are allowed).
- Cohort 2: Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.
- Cohort 3: Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.
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- Cohort 4: Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin of unknown primary site (excluding lung primary tumors) after progression to first-line chemotherapy with a platinum based regimen.
- For patients included in cohorts 1, 2 and 3: WHO Classification G1/G2 (mitotic count ≤10 mitoses x 10 HPF) lung typical and atypical carcinoids for cohort 1, G1/G2 (Ki67≤20% and mitotic count ≤20 mitoses x 10 HPF) gastrointestinal for cohort 2 (including stomach, small intestine and colorectal origins), G1/G2 (Ki67≤20% and mitotic count ≤20 mitoses x 10 HPF) pancreatic for cohort 3.
- For patients included in cohort 4: WHO classification G3 (Ki67>20% or mitotic count >20 mitoses x 10 HPF) gastroenteropancreatic neuroendocrine carcinomas (NEC) or liver metastases of G3 NEC of unknown primary site.
- Subjects must have evidence of measurable disease meeting the following criteria:
- In case of more than one target lesion, it should be identified at least 1 lesion of ≥ 1.0 cm in the longest diameter for a non lymph node, or ≥ 1.5 cm in the short-axis diameter for a lymph node, which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of ≥ 1.5 cm.
- Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation or liver embolization must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
- Subjects must show evidence of disease progression by radiologic image techniques within 12 months (an additional month will be allowed to accommodate actual dates of performance of scans, i.e., within ≤ 13 months) prior to signing informed consent, according to RECIST 1.1 .
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Adequate normal organ and marrow function as defined below: Haemoglobin ≥ 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.
- Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) 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.
Who cannot join
- Involvement in the planning and/or conduct of the study.
- Participation in another clinical study with an investigational product during the last 4 weeks.
- WHO Classification G3 neuroendocrine neoplasms of lung origin (oat cell/large cell lung cancer).
- Prior treatment with anti-PDL-1/anti-PD-1 or anti-CTL-4 therapy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B (e.g., HBsAg reactive), hepatitis C (e.g., HCV RNA [qualitative] is detected) or known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
- Known history of previous clinical diagnosis of tuberculosis.
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- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, 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.
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's 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 allogeneic organ transplant.
- History of hypersensitivity to durvalumab, tremelimumab or any excipient.
- Subjects having a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of trial treatment.
- Knowledge of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable brain metastases [without evidence of progression by imaging confirmed [by magnetic resonance imaging (MRI) if MRI was used at prior imaging, or confirmed by computed tomography (CT) imaging if CT used at prior imaging] for at least four weeks prior to the first dose of trial treatment; also, any neurologic symptoms must have returned to baseline], have no evidence of new or enlarging brain metastases,and have not used steroids for brain metastases for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab. Note: The killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines, and are not allowed.
- Subjects having known history of, or any evidence of interstitial lung disease or active, noninfectious pneumonitis.
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
- Subjects who have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. This does not apply to the use of somatostatin analogues for symptomatic therapy.
- Major surgery within 3 weeks prior to the first dose of study drug.
- Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24h will be ineligible.
- Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment.
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction.
- Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR)monitoring. Treatment with low molecular weight heparin (LMWH) is allowed.
- Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
- Patients with tumoral disease in the head and neck region, such as paratracheal or periesophageal lymph node involvement, or with infiltration of structures in the digestive tract, or vascular pathways that represent a risk of increased bleeding.
- Patients of cohort 1 with neuroendocrine tumors of pulmonary origin or pulmonary metastases with evidence of active bleeding.
- Patients with evidence of digestive bleeding.
- Active infection (any infection requiring treatment).
- Active malignancy (except for differentiated thyroid carcinoma, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.
- Documented active alcohol or drug abuse.
- Patients with a prior history of non-compliance with medical regimens.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Spain19 sites
Instituto Catalán de Oncología Badalona
Badalona, Barcelona
Hospital Duran i Reynals/ICO L'Hospitalet
Barcelona
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Universitario de Burgos
Burgos
Hospital Universitario Donostia
Donostia / San Sebastian
Hospital Universitario Virgen de las Nieves
Granada
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Gregorio Marañón
Madrid
Hospital Universitario HM Sanchinarro
Madrid
Hospital Universitario La Paz
Madrid
Hospital Universitario Ramón y Cajal
Madrid
Hospital Universitario Virgen de la Victoria
Málaga
Hospital General Universitario Morales Meseguer
Murcia
Complejo Hospitalario de Navarra
Pamplona, Navarre
Hospital Universitario de Canarias
Santa Cruz de Tenerife
Hospital Universitario Marqués de Valdecilla
Santander, Principality of Asturias
Hospital Universitario Virgen del Rocío
Seville
Hospital Universitario y Politécnico La Fe
Valencia
Hospital Universitario Miguel Servet
Zaragoza
About this study
Official title: A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for the Treatment of Patients With Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin (the DUNE Trial)
Well-differentiated gastroenteropancreatic and lung neuroendocrine tumors are generally malignancies with a prolonged natural history. However, clinical behavior is heterogeneous and when tumor progression is observed, treatment options are limited. The most used therapy for neuroendocrine tumors management are somatostatin analogs. However, even the use in lung carcinoids is quite usual, no antitumoral activity has been demonstrated. Tremelimumab and Durvalumab combination could be more efficient drugs to improve immune system activation and could obtain a significantly higher clinical benefit in these patients. Tremelimumab and Durvalumab would be the first immune combination agents showing efficacy in neuroendocrine neoplasms of different origins.
Read the detailed description
Prospective, multi-center, open label, stratified, exploratory, phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in different cohorts of patients with advanced/metastatic, histologically confirmed, grade 1/2 (G1/G2) of the 2010 WHO classification neuroendocrine tumors of the pancreas, gastrointestinal tract and lung origins and grade 3 (G3) of gastroenteropancreactic system or unknown primary site (excluding lung primaries) after progression to previous therapies.
- Being tested
- Durvalumab, Tremelimumab
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
Durvalumab, 1500 mg Q4W for 12 months.
TremelimumabDrug
Also called CP-675,206
Tremelimumab 75 mg Q4W for up to 4 doses/cycles.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab | Experimental | Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) for 12 months in patients ≥ 30kg.
Weight-based dosing should be used for patients <30 kg: durvalumab 20 mg/kg. Receives: Drug: Durvalumab |
| Tremelimumab | Experimental | Tremelimumab 75 mg Q4W (equivalent to 1 mg/kg Q4W) for up to 4 doses/cycles in patients ≥ 30kg.
Weight-based dosing should be used for patients <30 kg: tremelimumab 1 mg/kg Q4. Receives: Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate (CBR)
by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at month 9 after durvalumab plus tremelimumab was started. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions; SD as no changes in target lesions (i.e. <20% growth and <30% decrease). CBR = CR + PR +SD.
Some patients were not evaluable as they had no tumor assessments.
Measured: 9 months
Overall Survival
Time between start of treatment and death. Here we report the median time to death from any cause, estimated by Kaplan Meier method.
The times reported in here are the median time to event estimated by Kaplan Meier and that is why the number of months might be higher or lower than the overall and patient-specific follow-up.
Measured: Throughout the study period. Each patients has been followed approximately 24 months, up to 30 months.
Secondary outcomes (7)
Overall Response Rate
by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria.
dAssessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR
Measured: 9 months
Duration of Response
by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria.
Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions. Response = CR + PR
Measured: Throughout the study period, approximately 24 months
Progression Free Survival
by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria
Measured: Throughout the study period, approximately 24 months
Safety - Toxicities as Defined by CTCAE, v4.0
Based on subjects who experienced toxicities as defined by CTCAE, v4.0 The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications.
Measured: 9 months
Response Status
by irRECIST criteria, at 6, 9 and 12 months after start of study treatment. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR
Measured: 12 months
Response Status
by irRECIST criteria, at 6, 9 and 12 months after start of study treatment. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR
Measured: 9 months
Response Status
by irRECIST criteria, at 6, 9 and 12 months after start of study treatment. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2017
- Study start11 Apr 2017
- Primary completion30 Nov 2019
- Study completion23 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- The study includes a combined treatment of Durvalumab plus Tremelimumab
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Tumores Neuroendocrinos
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jaume Capdevila, M.D., Ph.D., Study chair, Hospital Universitari Vall d'Hebron, Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03095274
- Sponsor's protocol ID
- ESR 15-11561-61-DUNE
- Other IDs
- 2016-002858-20, 2016
- Acronym
- DUNE
- Status last verified
- Nov 2024
- First submitted
- 23 Mar 2017
- Last updated
- 9 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Capdevila J, Hernando J, Teule A, Lopez C, Garcia-Carbonero R, Benavent M, Custodio A, Garcia-Alvarez A, Cubillo A, Alonso V, Carmona-Bayonas A, Alonso-Gordoa T, Crespo G, Jimenez-Fonseca P, Blanco M, Viudez A, La Casta A, Sevilla I, Segura A, Llanos M, Landolfi S, Nuciforo P, Manzano JL. Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin. Nat Commun. 2023 May 23;14(1):2973. doi: 10.1038/s41467-023-38611-5.
PubMed 37221181
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab for the Treatment of Patients With Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin (the DUNE Trial)
- ClinicalTrials.gov ID
- NCT03095274
- Acronym / sponsor ID
- DUNE / ESR 15-11561-61-DUNE
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- Grupo Espanol de Tumores NeuroendocrinosUniversity, hospital or other
- Study start
- 11 Apr 2017 (actual)
- Primary completion
- 30 Nov 2019 (actual)
- Study completion
- 23 May 2022 (actual)
- First posted
- 29 Mar 2017 (actual)
- Results
- Posted 9 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Well-differentiated gastroenteropancreatic and lung neuroendocrine tumors are generally malignancies with a prolonged natural history. However, clinical behavior is heterogeneous and when tumor progression is observed, treatment options are limited. The most used therapy for neuroendocrine tumors management are somatostatin analogs. However, even the use in lung carcinoids is quite usual, no antitumoral activity has been demonstrated. Tremelimumab and Durvalumab combination could be more efficient drugs to improve immune system activation and could obtain a significantly higher clinical benefit in these patients. Tremelimumab and Durvalumab would be the first immune combination agents showing efficacy in neuroendocrine neoplasms of different origins.
Detailed description
Prospective, multi-center, open label, stratified, exploratory, phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in different cohorts of patients with advanced/metastatic, histologically confirmed, grade 1/2 (G1/G2) of the 2010 WHO classification neuroendocrine tumors of the pancreas, gastrointestinal tract and lung origins and grade 3 (G3) of gastroenteropancreactic system or unknown primary site (excluding lung primaries) after progression to previous therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study includes a combined treatment of Durvalumab plus Tremelimumab
| Arm | Type | Receives |
|---|---|---|
| Durvalumab | Experimental | Drug: DurvalumabDurvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) for 12 months in patients ≥ 30kg. Weight-based dosing should be used for patients <30 kg: durvalumab 20 mg/kg. |
| Tremelimumab | Experimental | Drug: TremelimumabTremelimumab 75 mg Q4W (equivalent to 1 mg/kg Q4W) for up to 4 doses/cycles in patients ≥ 30kg. Weight-based dosing should be used for patients <30 kg: tremelimumab 1 mg/kg Q4. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Written informed consent obtained from the subject prior to performing any protocol-related procedures.
- Age >18 years at time of study entry.
- Subjects must have histologically confirmed diagnosis of one of the following advanced/metastatic neuroendocrine tumor types:
- For patients included in cohorts 1, 2 and 3: WHO Classification G1/G2 (mitotic count ≤10 mitoses x 10 HPF) lung typical and atypical carcinoids for cohort 1, G1/G2 (Ki67≤20% and mitotic count ≤20 mitoses x 10 HPF) gastrointestinal for cohort 2 (including stomach, small intestine and colorectal origins), G1/G2 (Ki67≤20% and mitotic count ≤20 mitoses x 10 HPF) pancreatic for cohort 3.
- For patients included in cohort 4: WHO classification G3 (Ki67>20% or mitotic count >20 mitoses x 10 HPF) gastroenteropancreatic neuroendocrine carcinomas (NEC) or liver metastases of G3 NEC of unknown primary site.
Key exclusion criteria (32 listed)
- Involvement in the planning and/or conduct of the study.
- Participation in another clinical study with an investigational product during the last 4 weeks.
- WHO Classification G3 neuroendocrine neoplasms of lung origin (oat cell/large cell lung cancer).
- Prior treatment with anti-PDL-1/anti-PD-1 or anti-CTL-4 therapy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B (e.g., HBsAg reactive), hepatitis C (e.g., HCV RNA [qualitative] is detected) or known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: MEDI4736Durvalumab, 1500 mg Q4W for 12 months. | Drug | Durvalumab |
| TremelimumabAlso: CP-675,206Tremelimumab 75 mg Q4W for up to 4 doses/cycles. | Drug | Tremelimumab |
Primary outcome
Clinical Benefit Rate (CBR)
Time frame: 9 months
by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at month 9 after durvalumab plus tremelimumab was started. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as >=30% decrease in the sum of the longest diameter of target lesions; SD as no changes in target lesions (i.e. <20% growth and <30% decrease). CBR = CR + PR +SD. Some patients were not evaluable as they had no tumor assessments.
Overall Survival
Time frame: Throughout the study period. Each patients has been followed approximately 24 months, up to 30 months.
Time between start of treatment and death. Here we report the median time to death from any cause, estimated by Kaplan Meier method. The times reported in here are the median time to event estimated by Kaplan Meier and that is why the number of months might be higher or lower than the overall and patient-specific follow-up.
7 secondary outcomes
Overall Response Rate
Time frame: 9 months
Duration of Response
Time frame: Throughout the study period, approximately 24 months
Progression Free Survival
Time frame: Throughout the study period, approximately 24 months
Safety - Toxicities as Defined by CTCAE, v4.0
Time frame: 9 months
Response Status
Time frame: 12 months
Response Status
Time frame: 9 months
Response Status
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37221181Capdevila J, Hernando J, Teule A, Lopez C, Garcia-Carbonero R, Benavent M, Custodio A, Garcia-Alvarez A, Cubillo A, Alonso V, Carmona-Bayonas A, Alonso-Gordoa T, Crespo G, Jimenez-Fonseca P, Blanco M, Viudez A, La Casta A, Sevilla I, Segura A, Llanos M, Landolfi S, Nuciforo P, Manzano JL. Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin. Nat Commun. 2023 May 23;14(1):2973. doi: 10.1038/s41467-023-38611-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaume Capdevila, M.D., Ph.D. study chair
Hospital Universitari Vall d'Hebron, Barcelona
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab and Tremelimumab in people with Neuroendocrine Tumors and Neuroendocrine Neoplasm of Lung, run by Grupo Espanol de Tumores Neuroendocrinos at 19 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Benefit Rate (CBR) (time frame: 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03095274, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2025.