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

Rekrutierend

NCT-Nummer:
NCT03767075

Studienbeginn:
Dezember 2018

Letztes Update:
25.04.2024

Wirkstoff:
Atezolizumab, Futibatinib, Amivantamab

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Vall d'Hebron Institute of Oncology

Collaborator:
Roche Pharma AG, Iqvia Pty Ltd, Taisho Pharmaceutical Co., Ltd., Janssen, LP,

Studienleiter

Jordi Rodon, MD
Study Chair
MD Anderson

Kontakt

Studienlocations
(3 von 8)

Deutsches Krebsforschungszentrum (NCT/DKFZ)
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Richard Schlenk, MD
E-Mail: richard.schlenk@nct-heidelberg.de» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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 module 1 of part B (iBASKET) will receive atezolizumab 1200 mg IV

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. Module 1 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

120 participants being recruited into module 1 of part B (iBASKET).

Participants taking part in module 2 of part B (iBASKET) will receive will receive

futibatinib, 20 mg, once daily (QD) in 28-day cycles, following the analysis of their tumour

in part A (iPROFILER). Participants will be able to take futibatinib 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. Module 2 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, futibatinib. Approximately 1000 participants will be enrolled into part A

(iPROFILER), with approximately 80 participants being recruited into module 2 of part B

(iBASKET).

Participants taking part in module 3 of part B (iBASKET) will receive amivantamab 1050 mg IV

for body weight < 80 kg and 1400 mg for body weight >= 80 kg mg once weekly in Cycle 1 (with

a split dose on Days 1-2) and then every 2 weeks in subsequent cycles (28-day cycles),

following the analysis of their tumour in part A (iPROFILER). Participants will be able to

take amivantamab 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. Module 3 will have a 2.5-year

recruitment period. The aim of the study is to determine which genomically selected

populations respond effectively to the targeted treatment, amivantamab. Approximately 1725

participants will be enrolled into part A (iPROFILER), with approximately 69 participants

being recruited into module 3 of part B (iBASKET).

Ein-/Ausschlusskriterien

Eligibilty Criteria (PART A - iPROFILER)

Inclusion Criteria:

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. Patient 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.

5. Subjects must have enough tumour tissue for molecular analysis.

1. Subjects providing formalin-fixed paraffin embedded tissue (FFPE) must provide a

minimum amount of tissue ranging from 28 to 36 slides depending on the sample

tumour cellularity. If there is not enough archival tissue to meet this

criterion, the patient must undergo a tumour biopsy.

2. Subjects providing fresh frozen tissue must provide 5 core biopsies or

equivalent.

Fresh frozen tissue must be preferentially collected from a tumour biopsy; hence,

subjects must have disease amenable to be biopsied. Otherwise, the patient should

have fresh frozen tumour tissue stored in a biobank or biorepository.

3. Efforts will be made to provide fresh frozen tissue in at least one quarter of

the participating subjects. The proportion of subjects that might provide fresh

frozen tissue might change based on the results from the molecular analysis.

4. Since some of the tests are performed in FFPE tissue, subjects providing fresh

frozen tissue from a recent biopsy will have part of the sample processed in FFPE

as per Laboratory manual.

6. Subjects must have adequate haematological, renal, and hepatic function.

7. For subjects requiring a tumour biopsy: subjects must have adequate coagulation

function.

8. Subjects must be willing to participate in a clinical trial with a matched therapy

according to the molecular profile of his/her tumour.

Exclusion Criteria:

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 < 50%, unstable angina pectoris,

cardiac arrhythmia, or psychiatric illness/social situations that would limit

compliance with study requirements.

5. Subjects with inability to swallow tablets or capsules.

6. Subjects with known HIV, hepatitis B or hepatitis C infection.

7. Subjects with known history of malabsorption.

Eligibilty Criteria (PART B - iBASKET)

Inclusion Criteria:

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 for which standard therapy does not exist, or subjects may be

unable to receive standard therapy.

2. Patient 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.

5. Subjects must be willing to participate in a clinical trial with a matched therapy

according to the molecular profile of his/her tumour.

6. Tumours must harbour the following alterations.

7. Subjects must have adequate hematological, renal, and hepatic function.

8. For subjects requiring a tumour biopsy: subjects must have adequate coagulation

function.

9. A woman of childbearing potential must have a negative serum pregnancy test within 72

hours of the first dose of study treatment and must agree to further serum or urine

pregnancy test during the study.

10. A woman must be either of the following:

1. Not of childbearing potential.

2. Of childbearing potential and practicing true abstinence during the entire period

of the study, including up to 6 months after the last dose of study treatment is

given.

3. Of childbearing potential and practicing 2 methods of contraception, including 1

highly effective user independent method and a second method. Participant must

agree to continue contraception throughout the study and through 6 months after

the last dose of study treatment.

11. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted

reproduction during the study and for 6 months after receiving the last dose of study

treatment.

12. A male participant must agree not to donate sperm for the purpose of reproduction

during the study and for a minimum of 6 months after receiving the last dose of study

treatment.

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

Exclusion Criteria:

1. Pregnant or breastfeeding women. Females of childbearing potential must have a

negative serum pregnancy test within 72 hours of the first dose of study treatment and

must agree to further serum or urine pregnancy test during the study.

2. Any approved anticancer therapy, including chemotherapy, hormonal therapy or

radiotherapy, within 3 weeks prior to initiation of study treatment; however, the

following are allowed:

1. Hormone-replacement therapy or oral contraceptives.

2. Somatostatin analogues for the treatment of symptoms related with neuroendocrine

tumours.

3. Gonadotropin-releasing hormone agonists or antiandrogens for prostate cancer.

4. Palliative radiotherapy for bone metastases > 2 weeks prior to Cycle 1, Day 1.

3. Treatment with an investigational agent within 3 weeks prior to Cycle 1, Day 1 (or

within five half-lives of the investigational product, whichever is longer).

4. Patients with recent major surgery or invasive procedure within 15 days before the

fist dose of the study drug.

5. Participant has unstable symptomatic brain metastases. A participant with asymptomatic

or previously treated and stable brain metastases may participate in this study.

a. Participants who have received definitive radiation or surgical treatment for

symptomatic or unstable brain metastases and have been clinically stable and

asymptomatic for at least 2 weeks before enrolment are eligible, provided they have

been either off corticosteroid treatment or are stable or tapering doses below 4 mg of

dexamethasone.

6. Patients with meningeal or leptomeningeal carcinomatosis.

7. Uncontrolled intercurrent illness including, but not limited to, active infection,

cardiovascular disease, or psychiatric illness/social situations that would limit

compliance with study requirements.

8. Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg). Note: Subjects

with a prior history of HBV demonstrated by positive hepatitis B core antibody are

eligible if they have at Screening 1) a negative HBsAg and 2) an HBV DNA (viral load)

below the lower limit of quantification, per local testing.

9. Positive hepatitis C antibody (anti-HCV). Note: Subjects with a prior history of HCV,

who have completed antiviral treatment and have subsequently documented HCV RNA below

the lower limit of quantification per local testing are eligible.

10. Significant cardiovascular disease, such as New York Heart Association cardiac disease

(Class III or greater), myocardial infarction within 3 months prior to Cycle 1, Day 1,

unstable angina or unstable clinically meaningful arrhythmias.

11. Another primary malignancy other than disease under study within 2 years prior to

Cycle 1 Day 1, unless consider at low risk of relapse at Investigator discretion.

12. Contraindications included in the product information of the drugs used in the study.

Other protocol specified criteria for each module. The study center will determine if

criteria for participation are met.

Studien-Rationale

Primary outcome:

1. Overall response rate (Time Frame - From the first dose date of study treatment to first CR or PR, whichever came earlier, up to 12 weeks (Module 1 & 3) and 16 weeks (Module 2)):
Proportion of patients with a partial response [PR] or complete response [CR] per RECIST v1.1.



Secondary outcome:

1. Progression free survival (PFS by RECIST 1.1) (Time Frame - From initiation of treatment to objective progression or death from any cause, whichever occurs first, up to two years):
Time from the first dose date of study treatment to the date of investigator-determined objective progression (according to RECIST 1.1) or death from any cause, whichever occurs first.

2. Overall Survival (Time Frame - From initiation of treatment to death from any cause, up to two years):
Time from beginning treatment to the time of death from any cause.

3. Duration of response (Time Frame - From documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death (up to apprixmatelly 6 months).):
Time from documentation of the first CR or PR to the time of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death.

4. Health-related quality of life (HRQoL) (Time Frame - Baseline up to data cut-off, up to two years.):
Assessed with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30)

5. Incidence and severity of adverse events (Time Frame - From initiation of treatment to 30 days (all adverse events), and 90 days (all SAEs and AESIs), then any SAE considered treatment-related.):
Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Studien-Arme

  • Experimental: Module 1 - Atezolizumab
    Genomically selected populations will all receive the same drug 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 Arm 1G: tumours with CDK12 mutations 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 120 patients in part B of module 1.
  • Experimental: Module 2 - Futibatinib
    Genomically selected populations will all receive the same drug Arm 2A: Known pathogenic FGFR1-3 mutations Arm 2B: Variants of unknown significance in FGFR1-3 with functional relevance or pathogenic FGFR4 mutations. Arm 2C: Highly amplified FGFR1-3 with high FGFR1-3 mRNA (with the exception of gastric and breast cancer) Arm 2D: Highly amplifiedFGFR1-3 without high FGFR1-3 mRNA (with the exception of gastric and breast cancer) Subjects will be recruited and allocated to arms according to their biomarker profile. It is assumed that 2000 subjects will need to be screened in part A in order to enroll 80 patients in part B of module 2.
  • Experimental: Module 3 - Amivantamab
    Genomically selected populations will all receive the same drug Arm 3A: kinase domain mutations/ MET fusion-genes (including intragene exon skipping MET-MET fusions) Arm 3B: MET copy number gain (equivalent CNG ≥6) (exception: colorectal cancer) Arm 3C: EGFR mutations (exception: primary lung malignancies) Subjects will be recruited and allocated to arms according to their biomarker profile. It is assumed that 1725 subjects will need to be screened in part A in order to enroll 69 patients in part B of module 3.

Geprüfte Regime

  • Atezolizumab:
    1200 mg, administered IV, once every 3 weeks
  • Futibatinib (TAS-120):
    20 mg administered orally, once daily (QD) continuously in 28-day cycles.
  • Amivantamab (JNJ-372):
    1050 mg administered IV for body weight < 80 kg and 1400 mg for body weight >= 80 kg mg once weekly in Cycle 1 (with a split dose on Days 1-2) and then every 2 weeks in subsequent cycles (28-day cycles)

Quelle: ClinicalTrials.gov


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