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A Modular Multi-Basket Trial to Improve Personalized Medicine in Cancer Patients (Basket of Baskets)

NCT03767075

Description:

The Global objective of this Basket of Basket study is to evaluate the antitumor activity of each matched therapies that will be evaluated through the study in small molecularly selected populations. The objective of module 1 will be to determine the overall response rate by RECIST 1.1 of atezolizumab in several arms. Subjects will be separated into arms depending on the mutations of their tumour. All patients in genomically selected populations will receive atezolizumab 1200 mg IV every 3 weeks

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Modular Multi-Basket Trial to Improve Personalized Medicine in Cancer Patients (Basket of Baskets)
  • Official Title: Basket of Baskets: A Modular, Open-label, Phase II, Multicentre Study To Evaluate Targeted Agents in Molecularly Selected Populations With Advanced Solid Tumours

Clinical Trial IDs

  • ORG STUDY ID: VHIO17002
  • SECONDARY ID: 2017-005108-89
  • SECONDARY ID: MO39164
  • NCT ID: NCT03767075

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
Arm 1 - atezolizumabModule 1 Arm 1 - atezolizumab

Purpose

The Global objective of this Basket of Basket study is to evaluate the antitumor activity of each matched therapies that will be evaluated through the study in small molecularly selected populations. The objective of module 1 will be to determine the overall response rate by RECIST 1.1 of atezolizumab in several arms. Subjects will be separated into arms depending on the mutations of their tumour. All patients in genomically selected populations will receive atezolizumab 1200 mg IV every 3 weeks

Detailed Description

      Basket studies are a new sort of clinical studies to identify patients with the same kind of
      mutations and treat them with the same drug, irrespective of their specific cancer type. In
      basket studies, depending on the mutation types, patients are classified into "baskets".
      Targeted therapies that block that mutation are then identified and assigned to baskets where
      patients are treated accordingly.

      This protocol has two parts: part A (iPROFILER), which includes the common procedures for
      tumor molecular profiling and treatment recommendation, and part B (iBASKET), which
      corresponds to the therapeutic portion The purpose of part A (iPROFILER) of this study is to
      test participants' tumour tissue in order to identify whether their tumour has certain
      mutations in cancer-related genes. It is known that gene mutations of tumours contribute to
      their origin and growth and determine whether the tumour will respond to particular cancer
      drugs. This test will provide information about potential targeted therapies that
      specifically attack those gene mutations. The purpose of part B (iBASKET) of this study is to
      offer participants a personalised anti-cancer treatment based on the gene mutations that are
      found in their tumour. Participants taking part in this module 1 of part B (iBASKET), in
      genomically selected populations, will receive atezolizumab 1200mg intravenously every 3
      weeks, following the analysis of their tumour in part A (iPROFILER). Participants will be
      able to take atezolizumab for as long as their tumour doesn't grow and for as long as they
      don't have any side-effects which prevent them from continuing treatment.

      The study will have a 2-year recruitment period. The aim of the study is to determine which
      genomically selected populations respond effectively to the targeted treatment, atezolizumab.
      Approximately 1000 participants will be enrolled into part A (iPROFILER), with approximately
      100 participants being recruited into module 1 of part B (iBASKET)."
    

Trial Arms

NameTypeDescriptionInterventions
Module 1 Arm 1 - atezolizumabExperimentalGenomically selected populations will all receive the same drug (6 groups of mutation will be evaluated) Arm 1A: BRCA1 or BRCA2 mutations Arm 1B: MLH1, MSH2, MSH6, or PMS2 mutations Arm 1C: tumors with POLE mutation, POLD1 mutation. Arm 1D: hypermutated tumors Arm 1E: tumors with other mutations in DNA-repair genes. Arm 1F: tumors with amplified PDL1 Subjects will be recruited and allocated to arms according to their biomarker profile. It is assumed that 1000 subjects will need to be screened in part A in order to enroll 100 patients in part B of module 1.
  • Arm 1 - atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  ECOG performance status of 0 or 1.

          -  18 year-old or older.

          -  Measurable disease according to RECIST 1.1.

          -  Enough tumor tissue for molecular analysis

          -  Patients providing formalin-fixed paraffin embedded tissue (FFPE) must provide a
             minimum amount of tissue ranging from 20 to 28 slides depending on the sample tumor
             cellularity. If there is not enough archival tissue to meet this criterion, the
             patient must undergo a tumor biopsy.

          -  Patients providing fresh frozen tissue must provide 4 core biopsies or equivalent.
             Fresh frozen tissue must be preferentially collected from a tumor biopsy; hence,
             patients must have disease amenable to be biopsied. Otherwise, the patient should have
             fresh frozen tumor tissue stored in a biobank or biorepository.

          -  Efforts will be made to provide fresh frozen tissue in at least one quarter of the
             participating patients.

               -  The proportion of patients that might provide fresh frozen tissue might change
                  based on the results from the molecular analysis.

          -  Since some of the tests are performed in FFPE tissue, patients providing fresh frozen
             tissue from a recent biopsy will have part of the sample processed in formalin-fixed
             paraffin embedded tissue (FFPE) as per Laboratory manual.

          -  Adequate hematological, renal and hepatic function:

          -  For patients requiring a tumor biopsy, patients must have adequate coagulation
             function

               -  Quick time ≥ 60%

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Known brain metastases or leptomeningeal disease

          -  Spinal cord compression not definitively treated with surgery and/or radiation.

          -  Uncontrolled intercurrent illness including, but not limited to, active infection,
             symptomatic congestive heart failure, LVEF < 50%, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Inability to swallow tablets or capsules

          -  Known HIV, hepatitis B or hepatitis C infection.

          -  Known history of malabsorption.

          -  Pregnant and lactating women
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate by RECIST 1.1
Time Frame:12 weeks
Safety Issue:
Description:For the purposes of the primary endpoint of this study, subjects will be evaluated for response and progression using the new international criteria proposed by the revised RECIST guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

Secondary Outcome Measures

Measure:Mean progression free survival (PFS by RECIST 1.1) of the subjects participating in iBASKET
Time Frame:through study completion, an average of 3 years.
Safety Issue:
Description:
Measure:Progression Free Survival (PFS by RECIST 1.1)
Time Frame:6 months.
Safety Issue:
Description:
Measure:Mean overall survival of subjects treated with targeted therapy in iBASKET
Time Frame:through study completion, an average of 3 years.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vall d'Hebron Institute of Oncology

Trial Keywords

  • Advanced Solid Tumor
  • Cancer
  • Atezolizumab
  • Immunotherapy

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