Triple-Combination Immunotherapy: DC-CIK + Anti-PD-1 + Radiofrequency Hyperthermia for Advanced Malignant Mesothelioma
NCT03393858 (internal ID: RF8-MM) was a Phase I/II prospective study at Capital Medical University Cancer Center, Beijing Shijitan Hospital, investigating whether a novel triple-combination regimen โ autologous DC-CIK adoptive cell therapy, anti-PD-1 checkpoint blockade, and radiofrequency hyperthermia via the Thermotron RF-8EX device โ could improve progression-free survival and quality of life in patients with advanced malignant mesothelioma who had failed or refused platinum-based chemotherapy. The trial was terminated due to insufficient patient enrollment โ only 10 patients were enrolled. This page documents the scientific rationale and contextualises the treatment approach against the current mesothelioma landscape.
About This Clinical Trial
Malignant mesothelioma is a rare and aggressive cancer arising from the mesothelial cells lining the pleural cavity, peritoneum, pericardium, or tunica vaginalis. Pleural mesothelioma is the most common form, strongly associated with asbestos exposure with a latency period of approximately 40 years. Despite its rarity globally, mesothelioma carries one of the worst prognoses of any solid tumour, with median overall survival historically limited to 12โ18 months after diagnosis with standard platinum-based chemotherapy. The immunosuppressive tumour microenvironment, the rarity of the disease limiting large-scale trials, and the absence of driver mutations amenable to targeted therapy have made mesothelioma one of oncology's most challenging indications.
NCT03393858 (internal ID: RF8-MM) was a Phase I/II prospective study sponsored by Capital Medical University and conducted at Capital Medical University Cancer Center, Beijing Shijitan Hospital โ the base of Dr. Jun Ren MD PhD's DC-CIK immunotherapy research programme. Registered in January 2018, the study aimed to investigate a scientifically ambitious triple-combination approach: autologous DC-CIK adoptive cell immunotherapy, anti-PD-1 checkpoint blockade (PD-1 being highly expressed on exhausted immune cells in mesothelioma's immunosuppressive tumour microenvironment), and radiofrequency hyperthermia via the Thermotron RF-8EX capacitive heating device. Each of these three modalities has scientific rationale as a standalone or paired approach in mesothelioma; their combination was designed to achieve a synergistic trimodal immune activation.
The study opened for enrollment in December 2017 with a target of advanced mesothelioma patients who had refused or failed platinum-based chemotherapy. However, NCT03393858 was ultimately terminated due to insufficient patient enrollment โ only 10 patients were enrolled before the study closed. The registry was last verified in February 2024 with the termination reason explicitly stated as 'The number of enrolled cases is insufficient.' Primary completion occurred in December 2021 and full study completion in June 2022. No results have been posted to ClinicalTrials.gov and no trial-specific publication has been identified.
The termination of this trial due to insufficient enrollment is consistent with the well-documented challenge of recruiting rare cancer patients into complex multi-modality investigational trials, particularly in specialised centres with limited catchment populations for mesothelioma. The triple combination tested in this study โ DC-CIK + anti-PD-1 + hyperthermia โ represents a mechanistically compelling but under-explored approach that remains relevant to the evolving mesothelioma treatment landscape, particularly as immunotherapy combinations have since achieved regulatory approval as first-line mesothelioma therapy.
NCT03393858 was explicitly terminated because too few patients could be enrolled. Only 10 patients participated. This trial is not accepting patients. If you have malignant mesothelioma and are exploring immunotherapy options, CancerFax can identify currently available trials and treatment access options.
Trial at a Glance
Key registry details for NCT03393858. This is a terminated study. Details are provided for scientific reference only.
NCT03393858 is closed due to insufficient enrollment. Contact CancerFax for currently available mesothelioma options.
Treatment Being Studied
NCT03393858 tested one of the most mechanistically ambitious immunotherapy combinations attempted in mesothelioma: autologous DC-CIK adoptive cell therapy, anti-PD-1 checkpoint blockade, and systemic radiofrequency hyperthermia via the Thermotron RF-8EX device. Each component was chosen for a distinct and complementary role in reversing mesothelioma's deeply immunosuppressive biology.
Mesothelioma presents a particularly challenging immunological environment: low tumour mutational burden, abundant immunosuppressive regulatory T cells (Tregs) and M2 macrophages, upregulated PD-L1 expression on tumour cells, and physical barriers from the pleural fluid or peritoneal disease that limit immune cell infiltration. No single modality adequately addresses all of these layers โ which is precisely why a triple-combination approach was scientifically rational.
How the therapy works (in simple terms)
How it is given
DC-CIK cells provide tumour-reactive effector cell volume. Anti-PD-1 prevents those cells from being switched off by the tumour microenvironment. Hyperthermia opens the tumour to immune infiltration and amplifies the immunogenic cell death cascade. Together, they address three sequential barriers to effective anti-mesothelioma immunity.
Who This Trial May Be For
The following eligibility criteria defined the patient population for NCT03393858. These are provided for scientific reference only โ this study is terminated and not recruiting.
A confirmed tissue diagnosis of malignant mesothelioma was required โ including pleural, peritoneal, pericardial, or other anatomical variants. Cytological confirmation alone was not sufficient.
Patients must have either refused first-line platinum-based chemotherapy or experienced disease progression after a maximum of one line of platinum-based therapy. This positioned the trial as both a first-line alternative (for chemotherapy-refusing patients) and a second-line option.
Patients aged 18โ80 years with an ECOG performance status of 0, 1, or 2 were eligible. The upper age limit of 80 is stricter than many mesothelioma trials, reflecting the intensity of the triple-combination protocol.
At least one measurable lesion per RECIST criteria was required. Haematological thresholds: WBC โฅ 3,000/ยตL, haemoglobin โฅ 9 g/dL, platelets โฅ 75,000/ยตL. Renal and hepatic: creatinine < 1.5 mg/dL, bilirubin < 1.5 mg/dL (โค 2.0 for Gilbert's syndrome), ALT/AST โค 2.5ร ULN.
Patients with active autoimmune disease (excluding autoimmune thyroid disease and vitiligo) were excluded โ a standard anti-PD-1 exclusion criterion. Patients with known active CNS metastases or carcinomatous meningitis were also excluded. Notably, patients with HIV or chronic hepatitis were excluded due to immunosuppression concerns.
Patients on chronic steroid or other immunosuppressive therapy were excluded. Steroids directly suppress both DC-CIK and endogenous T cell function, rendering the immunotherapy approach ineffective. A 6-week washout was required before enrollment.
Eligibility Criteria
The following criteria are taken directly from the ClinicalTrials.gov registry for NCT03393858. These are provided for scientific reference only โ this study is terminated.
check_circleInclusion Criteria โ May Be Eligible
- โHistological confirmation of malignant mesothelioma
- โRefused first-line platinum-based chemotherapy, OR disease progression after maximum one line of platinum-based therapy
- โEstimated life expectancy > 3 months
- โECOG performance status 0, 1, or 2
- โAge 18 to 80 years
- โMost recent major surgery, drug therapy, or radiation therapy for malignant tumours completed at least 4 weeks before enrollment
- โMeasurable disease per RECIST criteria
- โWBC โฅ 3,000/microliter
- โHaemoglobin โฅ 9 g/dL (prior transfusion acceptable)
- โPlatelets โฅ 75,000/microliter
- โPT-INR < 1.5 (or < 3 if receiving warfarin)
- โPTT < 1.5ร ULN
- โSerum creatinine < 1.5 mg/dL
- โBilirubin < 1.5 mg/dL (โค 2.0 mg/dL for Gilbert's syndrome)
- โALT and AST โค 2.5ร ULN
cancelExclusion Criteria โ May Not Be Eligible
- รParticipation in another clinical study with an investigational product within the last 6 weeks
- รHistory of active autoimmune disease (inflammatory bowel disease, SLE, ankylosing spondylitis, scleroderma, multiple sclerosis โ autoimmune thyroid disease and vitiligo permitted)
- รKnown active CNS metastases or carcinomatous meningitis
- รSerious intercurrent illness: cardiac disease (NYHA III or IV), hepatic disease, or other condition considered high risk by the investigator
- รMedical or psychological impediment to probable protocol compliance
- รActive urinary tract infection or HIV (confirmed by ELISA and Western Blot)
- รChronic hepatitis (HBV or HCV)
- รChronic steroid therapy or other immunosuppressants (azathioprine, cyclosporin A) โ must be discontinued for at least 6 weeks before enrollment
- รPregnancy or nursing (sexually active patients must use contraception during treatment and 4 months thereafter)
- รEvidence of interstitial lung disease
NCT03393858 is closed. These eligibility criteria are preserved for scientific documentation and to help patients understand the patient population this study was designed for. If you have malignant mesothelioma, contact CancerFax for currently available options.
Risks and Side Effects
Because NCT03393858 was terminated with only 10 patients and no results published, the risk profile below draws on the established safety literature for each of the three components individually. Specific adverse event data from this trial are unavailable.
Anti-PD-1 antibodies can produce immune-related adverse events (irAEs) affecting any organ system โ including pneumonitis (particularly relevant in mesothelioma patients with pre-existing pleural disease), colitis, hepatitis, endocrinopathies (hypothyroidism, adrenal insufficiency, diabetes), dermatitis, and โ less commonly โ neurological and cardiac toxicities. Grade 3โ4 irAEs occur in approximately 10โ15% of patients receiving anti-PD-1 monotherapy and may require systemic corticosteroids or permanent discontinuation. In the combination setting, irAE rates may be higher.
DC-CIK infusion has a well-established safety record across over 1,100 patients at Beijing Shijitan Hospital. Adverse events are predominantly mild: low-grade fever (most common), transient fatigue, mild headache, and occasional joint pain. No fatal adverse events attributable to DC-CIK infusion have been documented in this dataset. In the combination setting, the DC-CIK-related cytokine activation may contribute to irAE risk when concurrent with anti-PD-1.
Radiofrequency hyperthermia via capacitive devices like the Thermotron RF-8EX is generally well tolerated. Reported adverse effects include local skin heating and discomfort at the surface electrodes, mild burns at electrode sites, and transient pain during heating. Systemic effects are generally limited. Patients with subcutaneous metallic implants may be at higher risk. The Thermotron RF-8EX has been used in published cancer research without reports of serious systemic toxicity in published literature.
The strict exclusion of patients with active autoimmune disease (with the exception of autoimmune thyroid disease and vitiligo) reflects the clinical reality that anti-PD-1 checkpoint inhibitors can significantly exacerbate underlying autoimmune conditions. This exclusion criterion narrows the eligible mesothelioma population and contributed to the recruitment challenges that ultimately led to termination.
Patients eligible for this study had already failed or refused platinum-based chemotherapy, placing them in a high-risk clinical context with limited organ reserve, potential fluid-related complications from pleural or peritoneal disease, and baseline nutritional compromise. The triple combination's intensity โ requiring DC-CIK manufacturing, anti-PD-1 scheduling, and hyperthermia sessions โ imposes a significant practical burden on this population.
With only 10 patients enrolled and no results posted, the adverse event profile specifically from NCT03393858 cannot be characterised. The information below reflects the known safety profile of each component from broader published literature.
Trial Location and Hospital Information
NCT03393858 was conducted at Capital Medical University Cancer Center / Beijing Shijitan Hospital, Beijing, China (zip: 100038) โ the same institution as the companion esophageal cancer DC-CIK trials (NCT01691625 and NCT01691664) and the gene expression profiling DC-CIK study (NCT01906632). Dr. Jun Ren MD PhD is listed as the responsible principal investigator for this study. The Thermotron RF-8EX hyperthermia device used in this study has been deployed at Beijing Shijitan Hospital's peritoneal cancer and oncology departments, which also run one of China's leading cytoreductive surgery plus HIPEC programmes for peritoneal malignancies.
Beijing Shijitan Hospital, Capital Medical University Cancer Center, has published internationally on mesothelioma treatment โ including a 2022 study of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) in 110 patients with diffuse malignant peritoneal mesothelioma. The hospital combines DC-CIK immunotherapy expertise with interventional oncology capabilities relevant to mesothelioma. International patients with mesothelioma seeking advanced treatment options at this centre should contact CancerFax to explore access. โ VERIFY: Confirm current mesothelioma treatment availability and contact pathway at CMUCC before communicating to patients.
How CancerFax Can Help Patients With Malignant Mesothelioma
CancerFax is a global cancer navigation platform. For patients with advanced malignant mesothelioma seeking immunotherapy options โ including approved regimens, DC-CIK access, and active clinical trials โ we provide expert-led, structured navigation.
Our medical team reviews your pathology, histology (epithelioid, biphasic, or sarcomatoid), disease extent, prior treatment history, and performance status to identify appropriate currently approved immunotherapy options โ including nivolumab+ipilimumab and pembrolizumab+chemotherapy โ and whether you qualify for access in China or internationally.
DC-CIK immunotherapy at Capital Medical University Cancer Center remains available as a clinical programme. CancerFax can coordinate access to Dr. Jun Ren's DC-CIK programme โ either as monotherapy, in combination with checkpoint inhibitors, or alongside other treatment modalities โ for mesothelioma patients seeking this approach in Beijing.
The mesothelioma trial landscape has expanded significantly since NCT03393858 was designed in 2017. CancerFax tracks currently recruiting trials globally โ including novel immunotherapy combinations, CAR-T programmes for mesothelin-expressing mesothelioma, bispecific antibodies, and hyperthermia combination studies โ and can identify which are appropriate for your specific mesothelioma subtype and treatment history.
For patients with malignant peritoneal mesothelioma, Beijing Shijitan Hospital operates one of China's leading cytoreductive surgery plus HIPEC (CRS+HIPEC) programmes โ with a published dataset of 110 patients. CancerFax can explore access to this surgical programme for eligible patients alongside immunotherapy options.
For international patients seeking treatment at Beijing Shijitan Hospital, CancerFax provides practical support: medical visa guidance, accommodation near the hospital, interpreter coordination, and logistics for the treatment period. Mesothelioma patients often require extended stays due to the multimodal nature of their treatment planning.
Mesothelioma is rare, and treatment decisions are complex. CancerFax provides human-led, expert-supported navigation from first inquiry through treatment coordination. We do not replace your oncologist โ we help you access specialist pathways, global trials, and Beijing-based treatment options that may not be visible from your local centre.
CancerFax does not guarantee access to any specific treatment or clinical trial. Our role is to help patients access accurate information and appropriate pathways.
Frequently Asked Questions
Advanced Malignant Mesothelioma โ Looking for Immunotherapy Options?
This trial is closed, but the immunotherapy landscape for mesothelioma has changed significantly since 2017. Two first-line checkpoint inhibitor regimens are now approved, DC-CIK therapy remains accessible at Beijing Shijitan Hospital, and new trials are actively recruiting globally. Submit your records for a no-obligation case review.
The information on this page is for educational and patient-navigation purposes only. It does not replace medical advice, diagnosis, or treatment from a qualified physician. Clinical trial eligibility, enrollment, treatment decisions, and costs are determined only by the trial investigators, hospital, sponsor, and applicable regulations. CancerFax helps patients and families understand options and coordinate case review where appropriate, but does not guarantee trial acceptance, treatment response, or clinical outcome. All clinical decisions must be made in consultation with a qualified, licensed physician with access to the patient's complete medical information.
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