Pancreatic CancerPhase 2NCT02704156
SBRT Plus Pembrolizumab and Trametinib for Pancreatic Cancer
A Phase 2 study testing Cyberknife plus Pembrolizumab and Trametinib and Cyberknife plus Gemcitabine in people with Pancreatic Cancer, run by Changhai Hospital at 1 site in China.
Trial summary
Hypothesis: Survival benefits could be found in SBRT Plus Pembrolizumab and Trametinib compared with SBRT plus gemcitabine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Cyberknife plus Pembrolizumab and Trametinib and Cyberknife plus Gemcitabine
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteChina
- Study dates
- Oct 2016to Dec 2020
- 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
- Histologically confirmed pancreatic ductal adenocarcinoma with unequivocal first progression after surgery followed by chemotherapy
- Without any immunotherapy or targeted therapy
- A life expectancy of >3months
- ECOG of 0 to1
- Age of 18 years or older
- Analysis of surgical specimens showed KRAS mutations and positive immunohistochemical staining of PD-L1
Show all 10Show fewer
- Blood routine examination: Absolute neutrophil count (ANC) ≥ 1.5 ×109 cells/L, leukocyte count≥ 3.5 ×109 cells/L, platelets ≥ 70×109 cells/L, hemoglobin ≥ 8.0 g/dl
- Liver and kidney function tests: Albumin > 2.5 g/dL, total bilirubin < 3 mg/dL, creatinine < 2.0 mg/dL, AST<2.5 × ULN(Upper Limit of Normal)(0-64U/L), ALT<2.5 × ULN(0-64U/L)
- INR < 2 (0.9-1.1)
- Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior immunotherapy or targeted therapy
- Evidences of metastatic disease confirmed by chest CT or FDG PET-CT
- Contraindication to receiving immunotherapy, targeted therapy or SBRT
- ECOG ≥2
- Age <18 years
- Analysis of surgical specimens showed KRAS wild type or negative immunohistochemical staining of PD-L1
Show all 16Show fewer
- Secondary malignancy
- Abnormal results of blood routine examinations and liver and kidney and coagulation tests
- Patients with active inflammatory bowel diseases or peptic ulcer
- Gastrointestinal bleeding or perforation within 6 months
- Heart failure: NYHA III-IV
- Respiratory insufficiency
- Women who are pregnant
- Participation in another clinical treatment trial while on study
- Patients in whom fiducial implantation was not possible
- Inability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Stereotactic Body Radiation Therapy Plus Pembrolizumab and Trametinib vs. Stereotactic Body Radiation Therapy Plus Gemcitabine for Locally Recurrent Pancreatic Cancer After Surgical Resection: an Open-label, Randomized, Controlled, Phase 2 Trial
Hypothesis: Survival benefits could be found in SBRT Plus Pembrolizumab and Trametinib compared with SBRT plus gemcitabine.
Read the detailed description
Background and aim:
Pancreatic cancer is one of the most lethal malignancies and fourth leading cause of cancer death in both genders in US, where the mortality and incidence increase over the past decade with a lowest 5-year survival rate of 9% among all cancers. Although surgical resection is deemed to provide long-term disease control, only 20% patients were candidates for upfront surgery and unfortunately, even when adjuvant chemotherapy is prescribed, about 50% of patients will suffer local recurrence. Despite of emergence of immunotherapy as a new treatment paradigm, little improvement of outcomes has been found in pancreatic cancer. This may be ascribed to its inherent genetic mutations and immunosuppressive microenvironment. It has been demonstrated that radiotherapy could enhance the release and uptake of tumor-associated antigens, thus promoting antitumor T cell priming, and enhancing access to tumors due to effects both on the tumor vasculature and the chemokine milieu.
Despite of emergence of immune checkpoint inhibitors as a novel treatment paradigm for cancers, the results of investigations about the efficacy of immunotherapy alone for pancreatic cancer was disappointing. Due to enhanced immunogenicity of tumor irradiation, the underlying rationale of combination of radiotherapy and immunotherapy is that radiation can noninvasively prime the immune system against tumor cells, where antigen presentation and co-stimulation are facilitated, thus creating immune responses against previously hidden epitopes that are shared among distant metastases, while immune checkpoint inhibitors can reverse the immunosuppressive effects of the tumor microenvironment, thus facilitating antitumor immunity.
Although oncogenic mutations in KRAS are frequent in pancreatic cancer, KRAS proteins are difficult to be targeted due to high affinity for GTP and/or GDP. Therefore, efforts have been made to develop therapies targeting the major downstream effector pathways, which include the RAS-RAF-MEK-ERK and PI3K-PDPK1-AKT signaling pathways. MEK inhibitor trametinib alone or in combinations with chemotherapy or autophagy inhibitor hydroxychloroquine may probably have positive effects on tumor regression.
Regarding local recurrence after surgery, it was recommended that chemotherapy with optional radiotherapy may be the first-line treatment without addition of targeted therapy or immunotherapy owing to that no studies have investigated the efficacy of this regimen. Therefore, the aim of our study was to compare the outcomes between stereotactic body radiation therapy (SBRT) with pembrolizumab and trametinib and SBRT with gemcitabine for locally recurrent pancreatic cancer after surgical resection.
Study procedure:
- All surgical specimens underwent immunohistochemical staining of PD-L1, classified as TC3 ≥ 50% or TC2 ≥ 5% but < 50% or TC1 ≥ 1% but <5% and IC3 ≥ 10% or IC2 ≥ 5% but < 10% or IC1 ≥ 1% but <5%.
- KRAS mutations were analyzed by PCR amplification and direct sequencing of exon 2. Restriction Length Fragment Polymorphism method was used for further confirmation.
- In the SBRT plus pembrolizumab and trametinib group, 200mg pembrolizumab was administered intravenously every 3 weeks and 2mg trametinib was given orally once daily.
- In the SBRT plus gemcitabine group, patients received intravenous gemcitabine (1000mg/m2) on day 1 and 8 of each 21-day cycle for eight cycles in the absence of disease progression.
- The prescribed dose of SBRT varies from 35-40Gy/5f with a single dose of 7-8Gy.
- Conditions
- Pancreatic Cancer
- Being tested
- Cyberknife plus Pembrolizumab and Trametinib, Cyberknife plus Gemcitabine
- Keywords
- Stereotactic body radiation therapy, CyberKnife, Initial treatment
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyberknife plus Pembrolizumab and TrametinibDevice
Radiation therapy plus drug
Cyberknife plus GemcitabineDevice
Radiation therapy plus drug
| Study group | Role | What they receive |
|---|---|---|
| SBRT plus Pembrolizumab and Trametinib | Experimental | Patients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine. Receives: Device: Cyberknife plus Pembrolizumab and Trametinib |
| SBRT plus Gemcitabine | Active comparator | Patients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine. Receives: Device: Cyberknife plus Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Median Survival Time Will be Determined.
The time from the start of treatment to death
Measured: 3 years
Secondary outcomes (5)
One- and Two-year Overall Survival Rate Will be Determined.
The number of patients alive at 1 year and 2 years.
Measured: 2 year
Treatment-related Adverse Effects Will be Determined.
Treatment-related adverse effects are determined by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.
Measured: 3 years
The Median Progression Free Survival Time Will be Determined.
The time from the start of treatment until documentation of any clinical or radiological disease progression or death, whichever occurred first. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 3 years
One- and Two-year Progression Survival Rate Will be Determined. Will be Determined.
The proportion of patients without disease progressions at 1 year and 2 years.
Measured: 2 years
The Quality of Life Will be Analyzed.
The analysis of quality of life is based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). All scales and subscales range from 0 to 100. Regarding physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning and global health, higher scores may indicate better outcomes. In the case of fatigue, nausea and vomitting, pain, dyspnea, insomina, appetite loss, constipation, diarrhea and financial difficulties, lower scores may indicate better outcomes. Scales of all items are independent and not combined to compute a total score.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2020
- Study completionDec 2020
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 (16)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Changhai HospitalThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhang Huo Jun, Changhai Hospital
- Investigators
- Huo Jun Zhang, MD., PH.D, Principal investigator, Changhai Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02704156
- Sponsor's protocol ID
- ChanghaiHosp
- Status last verified
- Feb 2022
- First submitted
- 1 Mar 2016
- Last updated
- 13 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 May;70(3):145-164. doi: 10.3322/caac.21601. Epub 2020 Mar 5.
PubMed 32133645Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. doi: 10.1001/jama.2013.279201.
PubMed 24104372Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25.
PubMed 19706802Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, Duret H, Yagita H, Johnstone RW, Smyth MJ, Haynes NM. Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res. 2012 Jul 1;72(13):3163-74. doi: 10.1158/0008-5472.CAN-12-0210. Epub 2012 May 8.
PubMed 22570253Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010 Oct;33(8):828-33. doi: 10.1097/CJI.0b013e3181eec14c.
PubMed 20842054Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
PubMed 22658128Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res. 2004 Jun 15;64(12):4328-37. doi: 10.1158/0008-5472.CAN-04-0073.
PubMed 15205348Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM; Australian Pancreatic Cancer Genome Initiative; Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016 Mar 3;531(7592):47-52. doi: 10.1038/nature16965. Epub 2016 Feb 24.
PubMed 26909576McCormick F. KRAS as a Therapeutic Target. Clin Cancer Res. 2015 Apr 15;21(8):1797-801. doi: 10.1158/1078-0432.CCR-14-2662.
PubMed 25878360Eser S, Schnieke A, Schneider G, Saur D. Oncogenic KRAS signalling in pancreatic cancer. Br J Cancer. 2014 Aug 26;111(5):817-22. doi: 10.1038/bjc.2014.215. Epub 2014 Apr 22.
PubMed 24755884Vena F, Li Causi E, Rodriguez-Justo M, Goodstal S, Hagemann T, Hartley JA, Hochhauser D. The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy in Pancreatic Cancer Models by Altering Ribonucleotide Reductase Subunit-1 (RRM1). Clin Cancer Res. 2015 Dec 15;21(24):5563-77. doi: 10.1158/1078-0432.CCR-15-0485. Epub 2015 Jul 30.
PubMed 26228206Kinsey CG, Camolotto SA, Boespflug AM, Guillen KP, Foth M, Truong A, Schuman SS, Shea JE, Seipp MT, Yap JT, Burrell LD, Lum DH, Whisenant JR, Gilcrease GW 3rd, Cavalieri CC, Rehbein KM, Cutler SL, Affolter KE, Welm AL, Welm BE, Scaife CL, Snyder EL, McMahon M. Protective autophagy elicited by RAF-->MEK-->ERK inhibition suggests a treatment strategy for RAS-driven cancers. Nat Med. 2019 Apr;25(4):620-627. doi: 10.1038/s41591-019-0367-9. Epub 2019 Mar 4.
PubMed 30833748Bryant KL, Stalnecker CA, Zeitouni D, Klomp JE, Peng S, Tikunov AP, Gunda V, Pierobon M, Waters AM, George SD, Tomar G, Papke B, Hobbs GA, Yan L, Hayes TK, Diehl JN, Goode GD, Chaika NV, Wang Y, Zhang GF, Witkiewicz AK, Knudsen ES, Petricoin EF 3rd, Singh PK, Macdonald JM, Tran NL, Lyssiotis CA, Ying H, Kimmelman AC, Cox AD, Der CJ. Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nat Med. 2019 Apr;25(4):628-640. doi: 10.1038/s41591-019-0368-8. Epub 2019 Mar 4.
PubMed 30833752Zhu X, Liu W, Cao Y, Ju X, Zhao X, Jiang L, Ye Y, Zhang H. Effect of stereotactic body radiotherapy dose escalation plus pembrolizumab and trametinib versus stereotactic body radiotherapy dose escalation plus gemcitabine for locally recurrent pancreatic cancer after surgical resection on survival outcomes: A secondary analysis of an open-label, randomised, controlled, phase 2 trial. EClinicalMedicine. 2022 Dec 1;55:101764. doi: 10.1016/j.eclinm.2022.101764. eCollection 2023 Jan.
PubMed 36471691Zhu X, Cao Y, Liu W, Ju X, Zhao X, Jiang L, Ye Y, Jin G, Zhang H. Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2022 Mar;23(3):e105-e115. doi: 10.1016/S1470-2045(22)00066-3.
PubMed 35240087
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stereotactic Body Radiation Therapy Plus Pembrolizumab and Trametinib vs. Stereotactic Body Radiation Therapy Plus Gemcitabine for Locally Recurrent Pancreatic Cancer After Surgical Resection: an Open-label, Randomized, Controlled, Phase 2 Trial
- ClinicalTrials.gov ID
- NCT02704156
- Acronym / sponsor ID
- ChanghaiHosp
- Conditions
- Pancreatic Cancer
- Keywords
- Stereotactic body radiation therapy, CyberKnife, Initial treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Study start
- Oct 2016 (actual)
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 9 Mar 2016 (estimated)
- Results
- Posted 16 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypothesis: Survival benefits could be found in SBRT Plus Pembrolizumab and Trametinib compared with SBRT plus gemcitabine.
Detailed description
Background and aim:
Pancreatic cancer is one of the most lethal malignancies and fourth leading cause of cancer death in both genders in US, where the mortality and incidence increase over the past decade with a lowest 5-year survival rate of 9% among all cancers. Although surgical resection is deemed to provide long-term disease control, only 20% patients were candidates for upfront surgery and unfortunately, even when adjuvant chemotherapy is prescribed, about 50% of patients will suffer local recurrence. Despite of emergence of immunotherapy as a new treatment paradigm, little improvement of outcomes has been found in pancreatic cancer. This may be ascribed to its inherent genetic mutations and immunosuppressive microenvironment. It has been demonstrated that radiotherapy could enhance the release and uptake of tumor-associated antigens, thus promoting antitumor T cell priming, and enhancing access to tumors due to effects both on the tumor vasculature and the chemokine milieu.
Despite of emergence of immune checkpoint inhibitors as a novel treatment paradigm for cancers, the results of investigations about the efficacy of immunotherapy alone for pancreatic cancer was disappointing. Due to enhanced immunogenicity of tumor irradiation, the underlying rationale of combination of radiotherapy and immunotherapy is that radiation can noninvasively prime the immune system against tumor cells, where antigen presentation and co-stimulation are facilitated, thus creating immune responses against previously hidden epitopes that are shared among distant metastases, while immune checkpoint inhibitors can reverse the immunosuppressive effects of the tumor microenvironment, thus facilitating antitumor immunity.
Although oncogenic mutations in KRAS are frequent in pancreatic cancer, KRAS proteins are difficult to be targeted due to high affinity for GTP and/or GDP. Therefore, efforts have been made to develop therapies targeting the major downstream effector pathways, which include the RAS-RAF-MEK-ERK and PI3K-PDPK1-AKT signaling pathways. MEK inhibitor trametinib alone or in combinations with chemotherapy or autophagy inhibitor hydroxychloroquine may probably have positive effects on tumor regression.
Regarding local recurrence after surgery, it was recommended that chemotherapy with optional radiotherapy may be the first-line treatment without addition of targeted therapy or immunotherapy owing to that no studies have investigated the efficacy of this regimen. Therefore, the aim of our study was to compare the outcomes between stereotactic body radiation therapy (SBRT) with pembrolizumab and trametinib and SBRT with gemcitabine for locally recurrent pancreatic cancer after surgical resection.
Study procedure:
- All surgical specimens underwent immunohistochemical staining of PD-L1, classified as TC3 ≥ 50% or TC2 ≥ 5% but < 50% or TC1 ≥ 1% but <5% and IC3 ≥ 10% or IC2 ≥ 5% but < 10% or IC1 ≥ 1% but <5%.
- KRAS mutations were analyzed by PCR amplification and direct sequencing of exon 2. Restriction Length Fragment Polymorphism method was used for further confirmation.
- In the SBRT plus pembrolizumab and trametinib group, 200mg pembrolizumab was administered intravenously every 3 weeks and 2mg trametinib was given orally once daily.
- In the SBRT plus gemcitabine group, patients received intravenous gemcitabine (1000mg/m2) on day 1 and 8 of each 21-day cycle for eight cycles in the absence of disease progression.
- The prescribed dose of SBRT varies from 35-40Gy/5f with a single dose of 7-8Gy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SBRT plus Pembrolizumab and Trametinib | Experimental | Device: Cyberknife plus Pembrolizumab and TrametinibPatients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine. |
| SBRT plus Gemcitabine | Active comparator | Device: Cyberknife plus GemcitabinePatients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed pancreatic ductal adenocarcinoma with unequivocal first progression after surgery followed by chemotherapy
- Without any immunotherapy or targeted therapy
- A life expectancy of >3months
- ECOG of 0 to1
- Age of 18 years or older
Key exclusion criteria (16 listed)
- Prior immunotherapy or targeted therapy
- Evidences of metastatic disease confirmed by chest CT or FDG PET-CT
- Contraindication to receiving immunotherapy, targeted therapy or SBRT
- ECOG ≥2
- Age <18 years
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 |
|---|---|---|
| Cyberknife plus Pembrolizumab and TrametinibRadiation therapy plus drug | Device | SBRT plus Pembrolizumab and Trametinib |
| Cyberknife plus GemcitabineRadiation therapy plus drug | Device | SBRT plus Gemcitabine |
Primary outcome
The Median Survival Time Will be Determined.
Time frame: 3 years
The time from the start of treatment to death
5 secondary outcomes
One- and Two-year Overall Survival Rate Will be Determined.
Time frame: 2 year
Treatment-related Adverse Effects Will be Determined.
Time frame: 3 years
The Median Progression Free Survival Time Will be Determined.
Time frame: 3 years
One- and Two-year Progression Survival Rate Will be Determined. Will be Determined.
Time frame: 2 years
The Quality of Life Will be Analyzed.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32133645Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 May;70(3):145-164. doi: 10.3322/caac.21601. Epub 2020 Mar 5.
- Background: PubMed 24104372Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013 Oct 9;310(14):1473-81. doi: 10.1001/jama.2013.279201.
- Background: PubMed 19706802Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25.
- Background: PubMed 22570253Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, Duret H, Yagita H, Johnstone RW, Smyth MJ, Haynes NM. Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res. 2012 Jul 1;72(13):3163-74. doi: 10.1158/0008-5472.CAN-12-0210. Epub 2012 May 8.
- Background: PubMed 20842054Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010 Oct;33(8):828-33. doi: 10.1097/CJI.0b013e3181eec14c.
- Background: PubMed 22658128Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
- Background: PubMed 15205348Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res. 2004 Jun 15;64(12):4328-37. doi: 10.1158/0008-5472.CAN-04-0073.
- Background: PubMed 26909576Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM; Australian Pancreatic Cancer Genome Initiative; Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016 Mar 3;531(7592):47-52. doi: 10.1038/nature16965. Epub 2016 Feb 24.
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- Individual participant dataSharing planned: Undecided
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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.
Huo Jun Zhang, MD., PH.D principal investigator
Changhai Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyberknife plus Pembrolizumab and Trametinib and Cyberknife plus Gemcitabine in people with Pancreatic Cancer, run by Changhai Hospital at 1 site in China.
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 10 inclusion and 16 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 13 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 16 Feb 2021). 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?
The Median Survival Time Will be Determined. (time frame: 3 years). 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 NCT02704156, which also lists 16 linked publications.
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 13 May 2022.