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

• ClinicalTrials.gov Identifier: NCT03767075
• Recruitment Status: Recruiting
• First Posted: December 6, 2018
• Last Update Posted: February 9, 2023
• Sponsor: Vall d'Hebron Institute of Oncology
• Collaborators: Roche Pharma AG; Iqvia Pty Ltd
• Information provided by (Responsible Party): Vall d'Hebron Institute of Oncology

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor	Drug: Arm 1 - atezolizumab	Phase 2

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)."

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1000 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment

Intervention Model Description

• Part A includes a molecular profiling program for subjects with advanced solid tumors (iPROFILER) and a molecular tumor board to select the most appropriate treatment based on the molecular alterations found in the iPROFILER.
• Part B includes iBASKET, a modular investigator initiated basket study for subjects with selected molecular alterations.

• Masking: None (Open Label)
• Masking Description: no masking is used. All involved know the identity of the intervention assignment
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 10, 2018
• Estimated Primary Completion Date: May 2025
• Estimated Study Completion Date: November 2026

Arms and Interventions

Arm

Intervention/treatment

Experimental: Module 1 Arm 1 - atezolizumab; Genomically 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.

Drug: Arm 1 - atezolizumab; Module 1 - 1200mg, IV, every 3 weeks, until progression or unacceptable toxicity develops.

Outcome Measures

Primary Outcome Measures :

1. Overall response rate by RECIST 1.1 [ Time Frame: 12 weeks ]
   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 :

1. 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. ]
2. Progression Free Survival (PFS by RECIST 1.1) [ Time Frame: 6 months. ]
3. Mean overall survival of subjects treated with targeted therapy in iBASKET [ Time Frame: through study completion, an average of 3 years. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Xenia Villalobos Alberú, PhD; +34 932 543 450 ext 8625; xvillalobos@vhio.net

Contact: Susana Muñoz; +34 934 893 000 ext 2432; smunoz@vhio.net

Locations

France

Institut Gustave Roussy; Recruiting

Villejuif, France, 94800

Contact: Christophe Massard

Germany

Deutsches Krebsforschungszentrum (NCT/DKFZ); Recruiting

Heidelberg, Baden-Wurtemberg, Germany, 69120

Contact: Richard Schlenk, MD

Netherlands

Nederland Kanker Instituut (NKI); Recruiting

Amsterdam, Netherlands, 1066

Contact: Frans Opdam, MD

Spain

Hospital Vall d'Hebron; Recruiting

Barcelona, Spain, 08035

Contact: Irene Braña, MD

Sweden

Karolinska University Hospital Solna; Recruiting

Stockholm, Sweden, 17176

Contact: Luigi de Petris, MD

United Kingdom

Cancer Research UK Cambridge Centre; Recruiting

Cambridge, United Kingdom, CB2 0QQ

Contact: Richard Baird, MD

Sponsors and Collaborators

Vall d'Hebron Institute of Oncology

Roche Pharma AG

Iqvia Pty Ltd

Investigators

• Study Chair: Jordi Rodon, MD; MD Anderson

More Information

• Responsible Party: Vall d'Hebron Institute of Oncology
• ClinicalTrials.gov Identifier: NCT03767075
• Other Study ID Numbers: VHIO17002; 2017-005108-89 ( EudraCT Number ); MO39164 ( Other Identifier: Roche Internal Identifier )
• First Posted: December 6, 2018
• Last Update Posted: February 9, 2023
• Last Verified: February 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Vall d'Hebron Institute of Oncology:

Advanced Solid Tumor; Cancer; Atezolizumab; Immunotherapy

Additional relevant MeSH terms:

Atezolizumab; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antineoplastic Agents