A phase 1/2 trial of EO2401, a novel microbial-derived peptide therapeutic vaccine, in combination with PD-1 check point blockade, for treatment ofpatients with locally advanced or metastatic adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma

Enterome0 个研究点目标入组 120 人开始时间: 2020年2月25日最近更新: 2024年7月15日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Enterome
入组人数: 120

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. For inclusion in Cohort 1 patients should have adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma, as defined below for Cohorts 2A and 3A.
•2. For inclusion in Cohorts 2A and 2B patients should have histologically confirmed (at primary diagnosis) unresectable locally advanced or metastatic (ENSAT/AJCC] stage 3=tumor has spread into nearby tissues or lymph nodes, or stage 4 = metastatic disease) adrenocortical carcinoma.
•a. In add., for inclusion in Cohort 2A patients should also have received treatment with at least one line, but not more than two prior lines, of systemic therapy for established locally advanced or metastatic disease (i.e. non-adjuvant therapy), and should within these lines of therapy for advanced/metastatic disease, or as neoadjuvant/adjuvant therapy, have received mitotane therapy delivered at an adequate dose.
•b. In add., for inclusion in Cohort 2B patients should not have received prior systemic therapy for established locally advanced or metastatic disease (i.e. non-adjuvant therapy). Note, for both Cohorts 2A and 2B, neoadjuvant/adjuvant therapy (incl. mitotane with or without chemotherapy) for patients after complete response to local therapy (e.g. resection) should not be counted in the definitions above for line of therapy for established disease. Patients who have received mitotane as neoadjuvant/adjuvant therapy, or therapy for advanced/metastatic disease can continue mitotane during study therapy provided definitions regarding eligibility of continued mitotane therapy are fulfilled.
•3. For inclusion in Cohorts 3A and 3B patients should have histologically confirmed (at primary diagnosis) unresectable malignant (defined as metastatic disease, i.e. presence of chromaffin tissue in non-chromaffin organs pheochromocytoma/paraganglioma, and RECIST defined progression should have been documented during a max of an 18months period.
•a. In add., for incl. in Cohort 3A patients should also have received treatment with at least two prior lines of systemic therapy if the patients are eligible for radionuclide therapy, and at least one prior line of systemic therapy if the patients are not eligible for radionuclide therapy.
•b. In add., for incl. in Cohort 3B patients should not have received prior systemic therapy for their malignant pheochromocytoma/paraganglioma.
•4. Patients with an age = 18 years old.
•5. Patients who are human leukocyte antigen (HLA)-A2 positive.
•6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status = 1 with the specific meaning of ECOG 1 being restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house-work, office work.
•7. Patients with a life expectancy > 4months as judged by their treating physician.
•8. Patients with at least one measurable lesion according to RECIST 1.1 (see Section 12.1).
•9. Males or non-pregnant, non-lactating, females who are: a) female, post-menopausal (serum follicle-stimulating hormone (FSH) level > 40 mIU/mL), b) female and male, surgically sterile (e.g. bilaterally blocked or removed fallopian tubes, vas deferens),
•c) female of childbearing potential with a negative highly sensitive serum pregnancy test within 72 hours prior to first administration of study treatment and use of a highly effective contraception from signing the ICF through 5 months after the last study treatment dose administered; note, the male partner should in

排除标准

•1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2401 administration, unless required to treat an adverse event. Note, inhaled steroids and adrenal replacement steroid doses > 13 mg daily prednisone equivalents are permitted. Thus, patients needing hydrocortisone replacement therapy due to prior or ongoing mitotane therapy can receive hydrocortisone doses > 53 mg/day, i.e. also in the normally used range of 60-80 mg/day, and still be included in the trial.
•2. Patients with prior treatment with compounds targeting PD-1, PD-L1, CTLA-4, or similar compounds where general resistance against therapeutic vaccination approaches might have developed (e.g. defects to the cellular antigen processing/presentation machinery, incl. mutations in Janus kinas [JAK] 1, JAK2, and ß-2-microglobulin [B2M]) allowing tumor cells to avoid recognition and attack by immune cells.
•3. Patients with prior exposure to EO2401, e.g. patients treated in Cohorts 2B or 3B of the current trial cannot be re-enrolled for treatment also in Cohorts 2A or 3A.
•4. Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other incl/excl criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2401 administration. Note, for patients with ACC continued treatment with mitotane during this trail is allowed provided patient is eligible (see section 6.9.2).
•For patients with MPP, concurrent therapy with somatostatin, and somatostatin analogues is allowed provided tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed.
•5. Patients with an initial diagnosis of ACC less than 9 months from start of screening part 2.
•6. Patients with ACC and any individual lesion according to RECIST 1.1 having a maximum diameter of more than 125 mm; irrespective if the lesion is proposed as a target lesion, or not, according to RECIST 1.1.
•7. Patients with ACC with more than three organs involved by disease.
•8. Patients with ACC and uncontrolled hormonal secretion (according to the judgement of the treating physician).
•9. Patients with MPP and uncontrolled blood pressure (according to the judgement of the treating physician).
•10. Patients with abnormal laboratory values according to the following list :
•a. lymphocyte count decreased, grade 2 (lymphocytes <800 - 500/mm3;
•<0.8 - 0.5 x 109/L), or worse grade,
•b. hemoglobin < 8 g/dL (9 mmol/L) i.e. anemia Grade 2 is acceptable if judged by the Investigator as not constituting a safety risk in the individual patient,
•c. white blood cell count decrease (< 3.0 × 109/L),
•d. absolute neutrophil count decrease (< 1.5 × 109/L), e. platelet count decrease (< 75 × 109/L),
•f. total bilirubin > 1.5 x upper limit of normal (ULN)
•g. alanine aminotransferase (ALT) > 3 x ULN; if disease metastatic to the liver > 5 x ULN,
•h. aspartate aminotransferase (AST) > 3 x ULN; if disease metastatic to the liver > 5 x ULN,
•i. serum creatinine increase (> 1.5 x ULN); however, if creatinine clearance (measured, or calculated according to the Cockcroft/Gault or the CKD-EPI equation) is > 40 mL/minute the patient can be enrolled,
•j. abnormal thyroid function

研究者

发起方

Enterome

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