Clinical trial NCT03671720: Personalized Vaccine Generated by Autologous Dendritic Cells Pulsed With Autologous Whole Tumor Cell Lysate Treat Advanced Solid Tumor Patients With High Tumor Mutation Burden
Official title: Personalized Vaccine Generated by Autologous Dendritic Cells Pulsed With Autologous Whole Tumor Cell Lysate Treat Advanced Solid Tumor Patients With High Tumor Mutation Burden
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Advanced Cancer
Metastatic Cancer
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Duke University
First posted: 2018-09-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is to investigate the safety and efficacy of dendritic cells vaccines pulsed with autologous whole tumor cell lysate for treating advanced solid tumor patients with high tumor mutation burden.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed advanced or metastatic solid tumors.
2. Patients must have received previously standard therapy for that malignancy or declined to chemotherapy/radiotherapy.
3. Estimated life expectancy \> 3 months
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
5. Age 18\~75 years old
6. Next-generation sequencing identified tumor mutation burden higher than 9 Muts/MB in tumor tissue or peripheral blood samples.
7. Available for the adequate surgical or core-needle biopsy specimens from primary or metastasis lesions to manufacture the DC vaccines.
8. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
9. Adequate hematologic function, with WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (it is acceptable to have had prior transfusion), platelets ≥ 75,000/microliter; PT-INR \<1.5 (unless patient is receiving warfarin in which case PT-INR must be \<3), PTT \<1.5X ULN
10. Adequate renal and hepatic function, with serum creatinine \< 1.5 mg/dL, bilirubin \< 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT and AST ≤ 2.5 x upper limit of normal.

Exclusion Criteria:

1. Patients with a history of autoimmune disease, such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune related thyroid disease and vitiligo are permitted.
2. Patients with serious intercurrent chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment.
3. Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
4. Concurrent (or within the last 5 years) second malignancy other than non melanoma skin cancer, cervical carcinoma in situ, controlled superficial bladder cancer, or other carcinoma in situ that has been treated.
5. Presence of an active acute or chronic infection including: a urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot). Patients with HIV are excluded based on immuno-suppression, which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections.
6. Patients on chronic steroid therapy (or other immuno-suppressives, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy (except that used as pre-medication for chemotherapy or contrast-enhanced studies or for acute treatment (\<5 days) of intercurrent medical condition such as a gout flare) prior to enrollment.
7. Pregnant and nursing women should be excluded from the protocol since this research may have unknown and harmful effects on an unborn child or on young children. If the patient is sexually active, the patient must agree to use a medically acceptable form of birth control while receiving treatment and for a period of 4 months following the last vaccination therapy. It is not known whether the treatment used in this study could affect the sperm and could potentially harm a child that may be fathered while on this study.
8. Patients with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.

Primary outcomes:
measure: Treatment-related adverse events
timeFrame: 12 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 6 months
measure: Progression-free survival of the participants(PFS)
timeFrame: 24 months
measure: Overall survival of the participants(OS)
timeFrame: 24 months
measure: The changes in immune-response specific patient-reported outcomes(irPRO)
timeFrame: 24 months
measure: The changes in patient self-reported quality of life
timeFrame: 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Medical University Cancer Center/Beijing Shijitan Hospital
state: Beijing
Study officials:
References: