Evident

2023-510092-62-00 Protocol 2020-01-v2 Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 27 Sep 2022 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol 2020-01-v2

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 45
Countries 1
Sites 1

Colorectal cancer

Pre-screening: Based on a tumor biopsy, establish a full combined pharmacogenomic profile which can be used to obtain an MTB-nominated treatment provided in the Main Study Main Study:  To evaluate the anti-tumor activity, measured as objective response rate (ORR) of MTB-nominated therapies with drugs not approved or…

Key facts

Sponsor
Oslo University Hospital HF
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Digestive System Diseases [C06]
Trial duration
27 Sep 2022 → ongoing
Decision date (initial)
2024-05-16
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes

External identifiers

EU CT number
2023-510092-62-00
EudraCT number
2020-003395-41
ClinicalTrials.gov
NCT05725200

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Pre-screening: Based on a tumor biopsy, establish a full combined pharmacogenomic profile which can be used to obtain an MTB-nominated treatment provided in the Main Study

Main Study:
 To evaluate the anti-tumor activity, measured as objective response rate (ORR) of MTB-nominated therapies with drugs not approved or implemented in SOC clinical practice for treatment of mCRC
 ORR will be assessed for the total population treated
 ORR in each study drug cohort

Secondary objectives 8

  1. Pre-screening: To assess the ability to obtain a tumor biopsy and full combined pharmacogenomic profile eligible for treatment decisions in a standard oncology practice, either  An MTB-nominated treatment provided in the Main Study  An MTB-nominated treatment considered as SOC  An MTB-nominated treatment not considered as SOC and not provided in the Main Study  No MTB-nominated
  2. Pre-screening: To evaluate the combined pharmacogenomic profiling from patient-derived organoids (PDOs) to predict clinical outcome of approved anticancer treatment (SOC) according to established treatment guidelines (Observational, in alignment with the translational project ‘SMART Liver’).
  3. Main study: To evaluate progressionfree survival (PFS) and duration of response (DOR) of participants receiving an MTB-nominated anticancer therapy
  4. Main study: To evaluate overall survival (OS of participants receiving MTB-nominated anti-cancer therapy
  5. Main study: To determine the safety and tolerability of the different MTB-nominated treatments provided in this study
  6. Main study: To assess the efficacy of MTB-nominated anticancer therapy compared to the efficacy of SOC achieved from first-line treatment in each patient
  7. Main study: To assess the efficacy of an MTB-nominated anticancer therapy compared to the efficacy achieved by the next line(s) of SOC treatment
  8. Main study: Describe patient-reported quality of life (QoL) during the MTB-nominated treatment

Conditions and MedDRA coding

Colorectal cancer

VersionLevelCodeTermSystem organ class
21.0 PT 10052358 Colorectal cancer metastatic 100000004864

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

  1. Pre-screeining: Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum
  2. Pre-screening: Has received or is receiving systemic treatment for mCRC
  3. Pre-screening: Has non-resectable metastases and eligible to undergo a radiological-guided core biopsy from at least one metastasis
  4. Pre-screening: ECOG performance status 0 or 1
  5. Pre-screening: Has measurable or evaluable disease (per RECIST v1.1)
  6. Pre-screening: Is capable of giving signed informed consent, as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
  7. Main studiy: Has a histologically-proven locally advanced or metastatic adenocarcinoma from colon or rectum (mCRC)
  8. Main studiy: Has received at least two lines of SOC chemotherapy for mCRC
  9. Main study: Has full combined pharmacogenomic profile (genomic and transcriptomic profile of the patients tumor and ex vivo drug sensitivity testing of PDOs from the patient’s own tumors cells) from which the MTB suggests a treatment with one of the defined targeted anti-cancer therapies provided this study
  10. Main study: Has measurable or evaluable disease (per RECIST v1.1)
  11. main Study: ECOG performance status 0 or 1
  12. Main study: For orally administered drugs, the participant must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
  13. Main study: Because of the risks of drug treatment to a developing fetus, women of child-bearing potential and men must agree to use adequate contraception in accordance with the respective SmPC
  14. Main study: Has acceptable organ function as defined below. However, as noted below (exclusion criteriom 16), drug-specific inclusion/exclusion criteria specified in the Appendix 16/respective SmPC for each agent will take precedence for this and all inclusion criteria:

Exclusion criteria 13

  1. Pree-screening: Has other clinically significant medical conditions which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements.
  2. Main study: Has ongoing toxicity > CTCAE grade 2, other than peripheral neuropathy and alopecia, related to anti-tumor treatment that was completed within 4 weeks prior to registration. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3 will be excluded.
  3. Main Study: Has received previous treatment with the selected study drug for the same malignancy
  4. Main study: Has a tumor with a genomic variant known to confer resistance to an anti-cancer agent available in this study, the patient will not be eligible to receive that agent but will be eligible to receive other drugs available in this study if all inclusion and exclusion criteria are met for that drug.
  5. Main study: Is receiving any other anti-cancer therapies (cytotoxic, biologic, radiation, or hormonal other than for replacement). Participants may be on warfarin, low molecular weight heparin or direct factor Xa inhibitors, unless such therapies are prohibited by drugspecific exclusion criteria (please consult the corresponding SmPC and Appendix 16 for prohibited medication and contraindication/precautions).
  6. Main study: Is pregnant or breastfeeding or refusing any type of required contraception methods.
  7. Main study: Has known CNS metastases.
  8. Main study: Has preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure.
  9. Main study: Has left ventricular ejection fraction (LVEF) known to be < 40%.
  10. Main study: Has had a stroke (including TIA) or an acute myocardial infarction within 6 months before the first dose of study treatment.
  11. Main study: Has had acute gastrointestinal bleeding within 1 month of start of treatment
  12. Main study: Has other clinically significant medical conditions which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements.
  13. Main study: Meets any of the assigned drug contraindications or other drug-specific exclusion criteria as described in the respective SmPC and in Appendix 16

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Pre-screening: Number of patients from whom organoids and a full combined pharmacogenomic profiling were established and eligible for considering an MTBnominated treatment provided in the Main Study
  2. Main study: Objective response rate (ORR) is a confirmed complete response (CR) or partial response (PR).  ORR in the total population.  ORR in each study drug cohort

Secondary endpoints 7

  1. Pre-screening: Number of patients from whom organoids and a full combined pharmacogenomic profile was established and eligible to have suggested:  An MTB-nominated treatment provided in the Main Study.  An MTB-nominated treatment considered as SOC.  An MTB-nominated treatment not considered as SOC and not provided in the Main Study.  No MTB-nominated treatment
  2. Pre-screening:  Registered outcome of all systemic SOC oncological treatment; objective response (OR), PFS and DOR.  OS from start of firstline SOC chemotherapy and OS from start of each line of SOC treatment
  3. Main study:  PFS, defined as the time from the first dose of the MTB-nominated treatment to the first documented disease progression or death due to any cause, whichever occurs first.  DOR, defined as the time from the first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating CR or PR
  4. Main study: OS, defined as the time from the first dose of MTB-nominated treatment to the date of death from any cause.  Classify and register adverse vents.
  5. Main study:  Assess ORR, DOR, PFS of MTB-nominated treatment and from the previous line of SOC treatment regimen in each patient.  Assess the number of patients who have a PFS of the MTB-nominated treatment which is >1.3 x PFS of the previous line of therapy.
  6. Main study: Assess ORR, DOR, PFS and of MTB-nominated treatment and form anticancer therapy in the next/later lines of SOC treatment in each patient
  7. Main study: Patient-reported outcome measures

Investigational products

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

Test 15

Talzenna 0.1 mg hard capsules

PRD11075869 · Product

Active substance
Talazoparib
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
1 mg milligram(s)
Max total dose
1 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01XK04 — -
Marketing authorisation
EU/1/19/1377/007
MA holder
PFIZER EUROPE MA EEIG
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

IBRANCE 100 mg hard capsules

PRD6520179 · Product

Active substance
Palbociclib
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
125 mg milligram(s)
Max total dose
125 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01EF01 — -
Marketing authorisation
EU/1/16/1147/003
MA holder
PFIZER EUROPE MA EEIG
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

XALKORI 250 mg hard capsules

PRD3362138 · Product

Active substance
Crizotinib
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
500 mg milligram(s)
Max total dose
500 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01ED01 — -
Marketing authorisation
EU/1/12/793/003
MA holder
PFIZER EUROPE MA EEIG
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Zydelig 100 mg film-coated tablets

PRD1682821 · Product

Active substance
Idelalisib
Substance synonyms
GS-1101
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
300 mg milligram(s)
Max total dose
300 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01XX47 — -
Marketing authorisation
EU/1/14/938/001
MA holder
GILEAD SCIENCES IRELAND UNLIMITED COMPANY
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Venclyxto 10 mg film-coated tablets

PRD6353823 · Product

Active substance
Venetoclax
Substance synonyms
ABT-199, GDC-0199, 4-(4-((2-(4-CHLOROPHENYL)-4,4-DIMETHYLCYCLOHEX-1-EN-1-YL)METHYL)PIPERAZIN-1-YL)-N-((3-NITRO-4-((TETRAHYDRO-2H-PYRAN-4-YLMETHYL)AMINO)PHENYL)SULFONYL)-2-(1H-PYRROLO(2,3-B)PYRIDIN-5-YLOXY)BENZAMIDE
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
400 mg milligram(s)
Max total dose
400 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01XX52 — -
Marketing authorisation
EU/1/16/1138/002
MA holder
ABBVIE DEUTSCHLAND GMBH & CO. KG
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Alecensa 150 mg hard capsules

PRD4815708 · Product

Active substance
Alectinib
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Max daily dose
1200 mg milligram(s)
Max total dose
1200 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01ED03 — -
Marketing authorisation
EU/1/16/1169/001
MA holder
ROCHE REGISTRATION GMBH
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Perjeta 420 mg concentrate for solution for infusion

PRD2154581 · Product

Active substance
Pertuzumab
Substance synonyms
rhuMAb 2C4, RG-1273, HLX11
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
840 mg milligram(s)
Max total dose
840 mg milligram(s)
Max treatment duration
6 Week(s)
Authorisation status
Authorised
ATC code
L01FD02 — -
Marketing authorisation
EU/1/13/813/001
MA holder
ROCHE REGISTRATION GMBH
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

SPRYCEL 20 mg film-coated tablets

PRD2341697 · Product

Active substance
Dasatinib
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
140 mg milligram(s)
Max total dose
140 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01EA02 — -
Marketing authorisation
EU/1/06/363/007
MA holder
BRISTOL-MYERS SQUIBB PHARMA EEIG
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Herceptin 150 mg powder for concentrate for solution for infusion

PRD2154035 · Product

Active substance
Trastuzumab
Substance synonyms
PF-05280014, TX05, BP02, ABP-980, SYD-977
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
8 mg/Kg milligram(s)/kilogram
Max total dose
8 mg/kg milligram(s)/kilogram
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01XC03 — TRASTUZUMAB
Marketing authorisation
EU/1/00/145/001
MA holder
ROCHE REGISTRATION GMBH
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Mektovi 15 mg film-coated tablets

PRD6728192 · Product

Active substance
Binimetinib
Substance synonyms
MEK162
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
90 mg milligram(s)
Max total dose
90 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01EE03 — -
Marketing authorisation
EU/1/18/1315/001
MA holder
PIERRE FABRE MEDICAMENT
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methotrexat Accord 25 mg/ml injeksjonsvæske, oppløsning

PRD1888176 · Product

Active substance
Methotrexate
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INJECTION
Max daily dose
50 mg/m2 milligram(s)/sq. meter
Max total dose
50 mg/m2 milligram(s)/sq. meter
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01BA01 — METHOTREXATE
Marketing authorisation
12-8858
MA holder
ACCORD HEALTHCARE B.V.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Farydak 20 mg hard capsules

PRD10403053 · Product

Active substance
Panobinostat
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
20 mg milligram(s)
Max total dose
20 mg milligram(s)
Max treatment duration
48 Week(s)
Authorisation status
Authorised
ATC code
L01XH03 — -
Marketing authorisation
EU/1/15/1023/007
MA holder
PHARMAAND GMBH
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Gemcitabine Accord 100 mg/ml konsentrat til infusjonsvæske

PRD1980155 · Product

Active substance
Gemcitabine
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSION
Max daily dose
1000 mg/m2 milligram(s)/square meter
Max total dose
1000 mg/m2 milligram(s)/square meter
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01BC05 — GEMCITABINE
Marketing authorisation
10-8088
MA holder
ACCORD HEALTHCARE B.V.
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Afinitor 10 mg tablets

PRD4008052 · Product

Active substance
Everolimus
Pharmaceutical form
TABLET
Route of administration
ORAL USE
Max daily dose
10 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
L01EG02 — -
Marketing authorisation
EU/1/09/538/008
MA holder
NOVARTIS EUROPHARM LIMITED
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323105 · Product

Active substance
Pembrolizumab
Substance synonyms
Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
400 mg milligram(s)
Max total dose
400 mg/g milligram(s)/gram
Max treatment duration
24 Month(s)
Authorisation status
Authorised
ATC code
L01FF02 — -
Marketing authorisation
EU/1/15/1024/002
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

73 Total trials 37 Recruiting 25 Ended
Academic / Non-commercial
Sponsor organisation
Oslo University Hospital HF
Address
Taarnbygget, Kirkeveien 166 Kirkeveien 166
City
Oslo
Postcode
0450
Country
Norway

Scientific contact point

Organisation
Oslo University Hospital HF
Contact name
Tormod Kyrre Guren

Public contact point

Organisation
Oslo University Hospital HF
Contact name
Tormod Kyrre Guren

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Norway Ongoing, recruiting 45 1
Rest of world — 0 —

Investigational sites

Norway

1 site · Ongoing, recruiting
Oslo University Hospital HF
Department for clinical research, Taarnbygget, Kirkeveien 166, Oslo

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2022-09-27 2023-10-05

Results and documents

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

Documents 18 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2023-510092-62-00 for publication 2.2
Protocol (for publication) D4_Patient facing documents questionnaire 3
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC gemcitabine accord NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC palcociclib ibrance NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC perjeta-pertuzumab NA
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC trastuzumab herceptin NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Alecensa NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC binimetinib mektovi NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC crizotinib xalkori NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC dasatinib sprycel NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC dasatinib sprycel NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC everolimus Afinitor NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC methotrexate NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC panobinostat farydak NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC pembrolizumab keytruda NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC talazoparib talzenna NA
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC venetoclax venclyxto NA
Synopsis of the protocol (for publication) D1_Protocol synopsis NO 2023-510092-62-00 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-04-12 Norway Acceptable
2024-05-08
 2024-05-16
2 SUBSTANTIAL MODIFICATION SM-1 2025-04-15 Norway Acceptable
2025-06-23
 2025-06-26

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