A modular multi-Basket trial to improve personalized medicine in cancer patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vall D Hebron Institute Of Oncology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Mar 2018 → ongoing

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Jannsen Pharma · Taihoo Pharma · Roche Farma

External identifiers

EU CT number

2024-514238-19-00

EudraCT number

2017-005108-89

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Efficacy

The primary objective is to evaluate the antitumour activity of each matched therapy in small subject populations as a signal finding study.

Conditions and MedDRA coding

Subjects with advanced solid tumour

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Part A: 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. (for 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 × 10 9/L, platelet count ≥ 100 × 10 9/L.
7. Subject must have adequate renal and hepatic function: Serum creatinine ≤ 1.5 × ULN and 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 tumour 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.
11. Part B: Inclusion criterion 2/3/4/6/8/9/10/12 from part A. 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.
12. 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: o Patients with documented liver metastases: AST and ALT < 5 x ULN o Patients with documented liver or bone metastases: alkaline phosphatase < 5 x ULN
13. Subjects receiving therapeutic anticoagulation (such as low−molecular weight heparin or warfarin) should be on a stable dose
14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from donating eggs, as described in the module protocol.
15. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined in the protocol. (Please refer to section 3.1 Inclusion Criteria of iProfiler, Module 1, 2 & 3 for full list)

Exclusion criteria 21

1. Part A 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.
8. Part B: Pregnant or breastfeeding women. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to Day 1. This negative test will be valid for Cycle 1 day 1. In subsequent cycles, serum pregnancy test will be performed on day 1 of each cycle, with a +/- 3 day window, and prior to drug administration.
9. Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed: •Hormone-replacement therapy or oral contraceptives. •Somatostatin analogues for the treatment of symptoms related with neuroendocrine tumours. •Gonadotropin-releasing hormone agonists or antiandrogens for prostate cancer. •Palliative radiotherapy for bone metastases > 2 weeks prior to Cycle 1, Day 1.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to Cycle 1, Day 1, unstable arrhythmias or unstable angina.
16. 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.
17. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, fusion proteins or any excipient of the experimental product.
18. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
19. Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. • Influenza vaccination can be given during influenza season only (example: approximately October to March in the Northern Hemisphere), but subjects must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
20. History of active tuberculosis
21. Contraindications included in the product information of the drugs used in the study. Please refer to section 3.2 Exclusion Criteria for full list of iProfiler and module protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Module 1, 2 & 3: • 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 ofatezolizumab 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vall D Hebron Institute Of Oncology

Sponsor organisation

Vall D Hebron Institute Of Oncology

Address

Calle Natzaret 115

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Vall D Hebron Institute Of Oncology

Contact name

Arantxa Romero Tamarit

Public contact point

Organisation

Vall D Hebron Institute Of Oncology

Contact name

Arantxa Romero Tamarit

Third parties 11

Locations

6 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 98 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications