Subjects with advanced solid tumor MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Sponsors
Vall d’Hebron Institute of Oncology (VHIO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A: 1. Subjects must have histologically or cytologically confirmed malignancy that is metastatic or unresectable, who have progressed to standard therapy, who are receiving a standard anticancer treatment but no subsequent approved treatment would be available upon progression, who are unable to receive standard therapy, or for whom standard therapy does not exist. 2. Subjects must have ECOG performance status of 0 or 1. 3. Subjects must be 18 year-old or older. 4. Subjects must have measurable disease according to RECIST 1.1. M1: Subjects with non-prostate solid tumours must have measurable disease according to RECIST 1.1 and patients with prostate cancer must have a tumour amenable to assess biochemical and/or objective radiographic responses according to PCWG3 and RECIST 1.1.) 5. Subjects must have enough tumour tissue for molecular analysis • Subjects providing formalin-fixed paraffin embedded tissue (FFPE) must provide a minimum amount of tissue ranging from 20 to 28 slides depending on the sample tumour cellularity. If there is not enough archival tissue to meet this criterion, the subject must undergo a tumour biopsy. • Subjects providing fresh frozen tissue (FFT) must provide 4 core biopsies or equivalent. FFT must be preferentially collected from a tumour biopsy; hence, patients must have disease amenable to be biopsied. Otherwise, the subject should have FFT stored in a biobank or biorepository. • Efforts will be made to provide FFT in at least one quarter of the participating subjects. The proportion of subjects that might provide FFT might change based on the results from the molecular analysis. • Since some of the tests are performed in FFPE tissue, patients providing FFT from a recent biopsy will have part of the sample processed in FFPE tissue as per Laboratory manual. 6. Subjects must have adequate hematological function: absolute granulocyte count = 1.5 × 109/L, platelet count = 100 × 109/L. 7. Subject must have adequate renal and hepatic function: creatinine clearance = 30ml/min, serum bilirubin =1.5 × ULN; unless due to Gilbert’s syndrome, AST/ALT =5 × ULN if liver metastases are present or AST/ALT =3 × ULN if the subject has no liver involvement. 8. For subjects requiring a tumor biopsy: patients must have adequate coagulation function quick time = 60% or INR =1.5 9. Subjects must be willing to participate in a clinical trial with a matched therapy according to the molecular profile of his/her tumour 10. Ability to understand and the willingness to sign a written informed consent document. Part B: Inclusion criterion 2/3/4/6/8/9/10/12 from part A 1. Subjects must have metastatic or unresectable malignant tumour, histologically or cytological confirmed and progressing to current therapy. Tumours must be refractory to standard therapy or tumours for which standard therapy does not exist, or subjects may be unable to receive standard therapy. 2. Subjects must have adequate renal and hepatic function as described in the module protocol:: • Serum creatinine = 1.5 × ULN or creatinine clearance = 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female)/72 × (serum creatinine in mg/dL) • Serum bilirubin = 1.5 × ULN; with the following exception: subjects with known Gilbert disease who have serum bilirubin level = 3 × ULN may be enrolled • AST, ALT and alkaline phosphatase < 2.5 x ULN, with the following exceptions: oPatients with documented li
Exclusion criteria
Exclusion criteria: Part A 1.Subjects with leptomeningeal disease should be excluded from this clinical trial. 2.Subjects with known unstable brain metastases should be excluded from this clinical trial. •Exception: Subjects who have undergone surgery and/or radiotherapy and in which brain metastases remain stable or decrease in size for six months after having completed therapy. 3.Subjects with spinal cord compression not definitively treated with surgery and/or radiation. 4.Subjects with uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, LVEF 2 weeks prior to Cycle 1, Day 1. 3.Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study. 4.Treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer), with the exception of monoclonal antibodies. Based on the half-life of monoclonal antibodies and the limited overlap on toxicities, a 4 week wash-out period will be allowed. 5.Subjects with known unstable brain metastases should be excluded from this clinical trial. •Exception: Subjects with treated brain metastasis which remain stable or responding 6 weeks after completing radiotherapy can be included. 6.Uncontrolled intercurrent illness including, but not limited to uncontrolled diabetes, active bleeding diathesis, impaired oxygenation requiring continuous oxygen supplementation, ophthalmologic condition that is clinically unstable, active infection, cardiovascular disease, or psychiatric illness/social situations that would limit compliance with study requirements. 7.Subjects with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. •Subjects with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. •Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 8.Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to Cycle 1, D
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the antitumor activity of each matched therapy in small subject populations as a signal finding study. ;Secondary Objective: To determine the prevalence of genetic alteration in the iPROFILER screened population. To evaluate the clinical benefit of matching therapies in small patient populations. To evaluate the safety and tolerability of each investigational agent tested as assessed by the incidence and severity of adverse events. Specific to Module 2&3: To assess the health-related quality of life (HRQoL) for all enrolled subjects.;Primary end point(s): Module 1 & 2: • Overall response rate (ORR) or complete response (CR) by RECIST 1.1 of different targeted agents in molecularly selected small patient populations. Specific to Module 1: * For patients with prostate cancer in arm 1G: ORR at 12 weeks of atezolizumab by a composite of biochemical and/or objective radiographic responses according to Prostate Cancer Working Group 3 (PCWG3) and RECIST 1.1. No specific primary endpoint in iProfiler (Part A) protocol.;Timepoint(s) of evaluation of this end point: At Week 12 (Module 1 & 3) At Week 16 (Module 2) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Specific Secondary Endpoints for iPROFILER part. •To determine the prevalence of genetic alterations in the iPROFILER screened population • Progression free survival (PFS by RECIST 1.1) of the patients treated with each investigational agent evaluated at the end of the module. *(M1) For patients with prostate cancer in arm 1G: PFS will be assessed by a composite of biochemical and/or objective radiographic progression according to PCWG3 and RECIST 1.1 for patients with prostate cancer. • Progression Free Survival (PFS by RECIST 1.1) at 6 months of subjects treated with targeted therapy with each investgational agents. • Overall survival (OS) of subjects treated with each investigational agent evaluated at the end of the module. - Incidence and severity of adverse events (AEs) in subjects receiving each investigational agent. Specific Secondary Endpoints for Module 2 & 3: • Duration of response (CR or PR), calculated from the date of initial documentation of a response to the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death. Data from subjects who are progression-free and alive or have unknown status will be censored at the last tumour assessment. Health-related quality of life (HRQoL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 items (EORTC-C30) and the 36-item Short Form health survey version 1 (SF36-v1). ;Timepoint(s) of evaluation of this end point: - Progression free survival at the end of the module. - Progression Free Survival at 6 months - Overall survival at the end of the module -Safety, continued evaluation during the trial Specific Secondary Endpoints for Module 2 &3: - at the last tumour assessment. - throughout the study course | — |
Countries
France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactSusana Munoz
Vall d’Hebron Institute of Oncology (VHIO)
Outcome results
None listed