A phase II, open-label, non-randomized, multi-center study evaluating the efficacy and safety of nivolumab plus ipilimumab in patients with cancer of unknown primary site who are relapsed after or refractory to platinum-based chemotherapy (CheCUP)

niversity Heidelberg, Med. Fac. repr. by University Hospital and its Commercial Managing Director0 个研究点目标入组 194 人开始时间: 2019年7月22日最近更新: 2022年5月30日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 194

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

•- Signed Informed Consent Form
•- Able and willing to comply with the study protocol
•- Age = 18 years at time of signing Informed Consent Form
•- Histologically-confirmed disseminated or advanced unresectable CUP diagnosed according the criteria defined in the 2015 ESMO Clinical Practice Guidelines for CUP. Acceptable disease histology includes:
•Adenocarcinoma of unknown primary site (ACUP)
•Poorly differentiated adenocarcinoma of unknown primary site
•Poorly differentiated carcinoma of unknown primary site
•Squamous cell carcinoma of unknown primary site (SCUP)
•- At least one lesion that is measurable according to RECIST v1.1 by CT/MRI
•- Availability of a tumor FFPE block either fresh or archival if obtained = 6 months at Screening that is sufficient for generation of a TruSight Oncology 500 (TSO500) panel at the central reference pathology laboratory or pre-existing result of a TMB analysis from routinely performed panel sequencing using the TSO500 panel at the MPZ, Institute of Pathology, University Heidelberg, which must not be older than < 6 months at screening, respectively. In case one attempt to perform TMB analysis on a new specimen has failed due to insufficient tumor cell quantity or insufficient quality in the specimen, or a re-biobsy has failed or cannot be performed for clinical or technical reasons, resorting to a specimen not older =24 months is allowed as an exception.
•- Availability of test reports confirming local CUP diagnosis. If test reports confirming local CUP diagnosis are not available, an FFPE block or a fresh biopsy sample must be submitted that is sufficient to allow for central confirmation of CUP diagnosis.
•- Disease relapse or progression after at least three cycles of a platinum-based standard chemotherapy. There is no upper limit of prior treatments received.
•- Subjects who have received prior surgery and/or radiotherapy and/or stereotactic brain metastasis radiosurgery are eligible. In case of prior radiotherapy, the measurable lesion(s) must not have been irradiated, radiotherapy has to be finished at least 7 days before start of study treatment and the patient must have recovered to grade 1 or less from any toxicity of radiotherapy.
•- ECOG performance status of 0 - 2
•- Life expectancy = 12 weeks
•- Eligible for immune checkpoint inhibitor
•- Adequate hematologic and end-organ function as detailed in the protocol (see section 4.4)
•- For women of childbearing potential and men capable of reproduction: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 5 months for women and 7 months for men, respectively after the last dose of study treatment.
•- Recovery from significant toxicity from platinum-doublet therapy to Grade = 1, except for alopecia and for neurosensory toxicity, which must be = 2
•- Recovery from active infections requiring intravenous antibiotics, with antibiotic therapy ceased for = 7 days prior to planned start of therapy
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 97
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 97

排除标准

•- Subjects with any of the specific non-CUP neoplasms identified in the ESMO CUP guidelines (Fizazi et al. 2015)
•- Subjects belonging to any of the following subsets of CUP with favorable prognoses
•- Known presence of brain or spinal cord metastasis, as determined by CT or magnetic resonance imaging (MRI) evaluation during screening. As an exception, patients with brain metastases are allowed to be included if all of the following five criteria are met:
•(i) the total number of brain metastases is 3 or less,
•(ii) brain metastases were / are asymptomatic,
•(iii) brain metastases have been completely surgically resected or completely treated with stereotactic radiosurgery
•(iv) there was / is no indication for whole-brain irradiation,
•(v) a brain MRI or high-resolution CT-scan at screening shows no evidence of residual disease
•- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
•- HIV infection
•- Positive for hepatitis C virus (HCV) infection at screening
•- Positive for hepatitis B surface antigen (HBsAg) at screening
•- Active tuberculosis at Screening
•- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia (including active ventricular arrhythmia requiring medication), or unstable angina
•- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
•- History of malignancy other than CUP within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
•- Solid organ Transplantation
•Prior allogeneic stem cell transplantation with follow-up < 1 year, need for systemic immunosuppression or active chronic graft-versus host disease (cGVHD)
•- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
•- Known allergy or hypersensitivity to any component of the immunotherapy, including history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins and to Chinese hamster ovary cell products or other recombinant human or humanized antibodies for nivolumab and ipilimumab.
•- Subjects with an autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, myocarditis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
•- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents), or other immuno-suppressive medications within 14 days of study treatment. Inhaled or topical steroids an

研究者

发起方

niversity Heidelberg, Med. Fac. repr. by University Hospital and its Commercial Managing Director

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