Single arm, open label, signal seeking, phase II trial of the activity of Palbociclib in combination with Avelumab in patients with tumours with amplified D-type cyclins or CDK4 or inactivation of CDKN2A.

The University of Sydney0 个研究点目标入组 64 人开始时间: 2020年5月15日最近更新: 2024年2月5日

适应症

试验速览

阶段: 2 期
状态: 进行中（未招募）
发起方: The University of Sydney
入组人数: 64

研究概览研究设计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
分配方式: Non-randomised trial
主要目的: Treatment
盲法: Open (masking not used)

入排标准

年龄范围: 18 Years 至 o limit（—）
性别: All

入选标准

•Inclusion Criteria – molecular screening:
•1. Male or female patients, aged 18 years and older, with pathologically confirmed advanced and/or metastatic cancer of any histologic type, including haematological cancers, or an earlier diagnosis of a poor prognosis cancer;
•2. Sufficient and accessible tissue for molecular screening;
•3. Patients receiving their last line of standard treatment or who have received and failed all standard anticancer therapy (where standard therapy exists) or have documented unsuitability for any further standard anticancer therapy. Poor prognosis cancers or cancers with low expected response rate to standard treatment (in the opinion of the investigator and based on available evidence) may be screened on an earlier line of treatment.
•a. Failure is defined as either progression of disease (clinical or radiological) or intolerance to standard therapy resulting in the discontinuation of the therapy.
•b. Documented unsuitability for further standard therapy includes known hypersensitivity, organ dysfunction or other patient factors that would make therapy unsuitable in the judgement of the responsible investigator;
•4. ECOG performance status 0, 1 or 2;
•5. Willing and potentially able to comply with study requirements, including treatment, timing and/or nature of required assessments; It is the intention to screen patients who are in principle wishing to take part in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase;
•It is the intention to screen patients who are in principle wishing to take part in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase (substudy).
•To be eligible for treatment in a substudy, patients must continue to meet all of the inclusion criteria and none of the exclusion criteria specified for entry into molecular screening at the time of registration to a treatment substudy. In addition, they must meet all the inclusion criteria and none of the exclusion criteria in the substudy addendum at the time of registration.
•Inclusion Criteria – substudy:
•1. Confirmation of molecular eligibility by the molecular tumour board; Patients with tumour harbouring
•a. Gain-of-function mutations in CDK4 or CCND1-3
•b. CDKN2A deletion or loss-of-function mutations
•2. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists;
•3. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance;
•4. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug):
•a. bone marrow function; platelets equal or greater than 100 x 10^9/L, ANC equal or greater than 1.5 x 10^9/L, and haemoglobin equal or greater than 9g/dL (5.6mmol/L); This will not apply for patients with haematological cancers if cytopenias are disease related;
•b. liver function; ALT/AST equal or less than 3 x ULN (in the absence of liver metastases, equal or less than 5 x ULN for patients with liver involvement) and total bilirubin equal or less than 1.5xULN;
•c. renal function; serum creatinine equal or less than 1.5xULN;
•5. Measurable disease by iRECIST and RECIST v 1.1 or RANO

排除标准

•Exclusions criteria - molecular screening
•1. Suitable for standard therapy or accepted standard care, if the patient has not been previously treated;
•2. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may contraindicate participation and/or interact with the investigational product;
•3. Other co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
•4. For non central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer are excluded. Subjects with stable neurological function on stable doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS progression within 12 weeks prior to screening are eligible;
•5. History of another malignancy within 2 years prior to molecular screening registration are excluded unless adequately treated and determined free of progressive and metastatic disease for at least 6 months. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder can be included;
•6. Pregnancy, lactation or inadequate contraception.
•Exclusion criteria - substudy
•1. Hormone positive breast cancer
•2. Contraindications to investigational product;
•3. Known history of hypersensitivity to active or inactive components of investigational product;
•4. Prior treatment with CDK4/6 inhibitor or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
•5. Prior treatment with checkpoint inhibitor
•6. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval
•7. QTc interval greater than 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
•8. Prolonged use of moderate to high doses of immunosuppressive medication before the first dose of avelumab. Exceptions include intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (eg. <=10 mg/day of prednisone; use of dexamethasone up to 4mg /day within 14 days of initial treatment for patients with brain tumours).
•9. Receipt of any organ transplantation including allogeneic stem-cell transplantation.
•10. Significant acute or chronic infections including, among others:
•a. Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
•b. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
•11. Active or history of any autoimmune disease (subjects with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
•12. Currently diagnosed with interstitial lung disease or pneumonitis
•13. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s);
•14. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
•15. Treatment with any of the following anti-cancer thera

研究者

发起方

The University of Sydney

相似试验

终止

2 期

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 16 substudy 37: PamiparibCancer - Leukaemia - Acute leukaemiaCancer - Leukaemia - Chronic leukaemiaCancer - ThrombocythaemiaCancer - Other cancer typesCancer

ACTRN12621001183875The University of Sydney12

招募中

2 期

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 9 substudy 21-22: Tucatinib andTrastuzumabCancer - Any cancerCancer

ACTRN12620000767909niversity of Sydney32

已完成

2 期

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 3 substudies 6 - 8: olaparib plus durvalumabCancer - Any cancerCancer

ACTRN12617001000392niversity of Sydney48

招募中

2 期

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 8 substudy 19: T-DM1Cancer - Any cancerCancer

ACTRN12619001265167The University of Sydney64

已完成

2 期

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 4 substudy 9: vismodegibCancer - Any cancerCancer

ACTRN12618000281291The University of Sydney16