The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs

NCT ID: NCT05159245

Last Updated: 2024-07-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-10
• Study Completion Date: 2026-11-25

Brief Summary

This is a prospective non-randomized national clinical phase 2 trial that aims to determine the efficacy and toxicity of targeted anticancer drugs or combinations that are approved or under review by EMA, FDA or PMDA and are used for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic, RNA-molecular or protein expression test.

Detailed Description

This is a prospective non-randomized clinical trial that aims to determine the efficacy and toxicity of targeted anticancer drugs or combinations that are approved or under review by EMA, FDA or PMDA and are used for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic, RNA-molecular or protein expression test. The study also aims to facilitate patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing and further deeper analysis on tumor biopsies and/or liquid biopsies for biomarker analyses and resistance mechanisms. Eligible patients have an advanced cancer for which standard treatment options no longer exist and acceptable performance status and organ function. A tumour DNA, RNA or protein expression analysis is required and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Molecular profiling will be utilized to determine an appropriate drug(s) from among those available in the protocol. Drug selection will be guided by a list of potential profiles, the molecular tumor board and databases of identified targets for review and approval of the recommended treatment. The protocol-specified treatment will be administered to the patient once any drug- and disease specific eligibility criteria and overall study criteria are met. Data for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment will be collected for all patients receiving treatment within the trial. In addition, treatment related toxicity will be collected according to CTCAE 5.0.

Conditions

Advanced Cancer; Solid Tumor; Haematological Malignancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alectinib

For patients with a molecular tumor profile that can potentially be targeted by alectinib.

Group Type: EXPERIMENTAL

Alectinib

Intervention Type: DRUG

ALK

Cobimetinib

For patients with a molecular tumor profile that can potentially be targeted by cobimetinib.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

MEK1, MEK2

Vismodegib

For patients with a molecular tumor profile that can potentially be targeted by vismodegib.

Group Type: EXPERIMENTAL

Vismodegib

Intervention Type: DRUG

Hedgehog

Trastuzumab+Pertuzumab

For patients with a molecular tumor profile that can potentially be targeted by trastuzumab+pertuzuma combination.

Group Type: EXPERIMENTAL

Trastuzumab+Pertuzumab

Intervention Type: DRUG

HER2

Entrectinib

For patients with a molecular tumor profile that can potentially be targeted by entrectinib.

Group Type: EXPERIMENTAL

Entrectinib

Intervention Type: DRUG

NTRK/ ROS1, ALK

Atezolizumab

For patients with a molecular tumor profile that can potentially be targeted by atezolizumab.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

PD-L1

Vemurafenib

For patients with a molecular tumor profile that can potentially be targeted by vemurafenib.

Group Type: EXPERIMENTAL

Vemurafenib

Intervention Type: DRUG

BRAF V600

Regorafenib

For patients with a molecular tumor profile that can potentially be targeted by regorafenib.

Group Type: EXPERIMENTAL

Regorafenib

Intervention Type: DRUG

KIT/BRAF, RET

Apalutamide

For patients with a molecular tumor profile that can potentially be targeted by apalutamide.

Group Type: EXPERIMENTAL

Apalutamide

Intervention Type: DRUG

AR

Abemaciclib

For patients with a molecular tumor profile that can potentially be targeted by abemaciclib.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

CDK4/6

Tepotinib

For patients with a molecular tumor profile that can potentially be targeted by tepotinib.

Group Type: EXPERIMENTAL

Tepotinib

Intervention Type: DRUG

MET ex14

Dabrafenib

For patients with a molecular tumor profile that can potentially be targeted by dabrafenib.

Group Type: EXPERIMENTAL

Dabrafenib

Intervention Type: DRUG

RAF

Trametinib

For patients with a molecular tumor profile that can potentially be targeted by trametinib.

Group Type: EXPERIMENTAL

Trametinib

Intervention Type: DRUG

MEK1, MEK2

Dabrafenib+Trametinib

For patients with a molecular tumor profile that can potentially be targeted by dabrafenib+trametinib combination.

Group Type: EXPERIMENTAL

Dabrafenib+Trametinib

Intervention Type: DRUG

RAF, MEK1, MEK2

Pemigatinib

For patients with a molecular tumor profile that can potentially be targeted by pemigatinib.

Group Type: EXPERIMENTAL

Pemigatinib

Intervention Type: DRUG

FGFR2

Interventions

Alectinib

ALK

Intervention Type: DRUG

Cobimetinib

MEK1, MEK2

Intervention Type: DRUG

Vismodegib

Hedgehog

Intervention Type: DRUG

Trastuzumab+Pertuzumab

HER2

Intervention Type: DRUG

Entrectinib

NTRK/ ROS1, ALK

Intervention Type: DRUG

Atezolizumab

PD-L1

Intervention Type: DRUG

Vemurafenib

BRAF V600

Intervention Type: DRUG

Regorafenib

KIT/BRAF, RET

Intervention Type: DRUG

Apalutamide

AR

Intervention Type: DRUG

Abemaciclib

CDK4/6

Intervention Type: DRUG

Tepotinib

MET ex14

Intervention Type: DRUG

Dabrafenib

RAF

Intervention Type: DRUG

Trametinib

MEK1, MEK2

Intervention Type: DRUG

Dabrafenib+Trametinib

RAF, MEK1, MEK2

Intervention Type: DRUG

Pemigatinib

FGFR2

Intervention Type: DRUG

Other Intervention Names

Alecensa; Cotellic; Erivedge; Phesgo; Rozlytrek; Tecentriq; Zelboraf; Stivarga; Erleada; Verzenio; Tepmetko; Tafinlar; Mekinist; Tafinlanr+Mekinist; Pemazyre

Eligibility Criteria

Inclusion Criteria

1. Adult (age >18 years) patient with a histologically-confirmed locally advanced or metastatic cancer who is no longer benefitting from standard anti-cancer treatment or for whom no such treatment is available or indicated.

2. ECOG performance status 0-2

Exclusion Criteria

1. Absolute neutrophil count ≥ 1.5 x 109/l

2. Hemoglobin > 8.0 mmol/l, without blood transfusion within 7 days

3. Platelets > 75 x 109/l (not applicable for hematological patients)

4. Total bilirubin < 1.5 x ULN

5. AST and ALT < 3 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases)

6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2

4. Patients must have objectively evaluable or measurable disease (by physical or radiographic examination, according to RECIST v1.1, Lugano, IWG and ELN-AML, IMWG, RANO, GCIG, iRESIST or PCWG3.

5. Results must be available from a tumor molecular profiling. Eligible tests may include any of the following technologies: fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), comparative genomic hybridization (CGH), next generation sequencing (NGS) or immunohistochemistry (IHC). The test may have been performed on the primary tumor or a metastatic lesion, in a diagnostic laboratory or within the context of another commercial platform (eg Foundation Medicine), and must reveal a potentially actionable variant.

6. Patients must have a tumor profile for which treatment with one of the approved (or under revision for approval) targeted anti-cancer drugs included in this study has potential clinical benefit based on preclinical data or clinical information.

7. A new (obtained ≤6 months before inclusion after which no further anti-cancer therapy is allowed) fresh frozen and FFPE tumor biopsy specimen or liquid biopsy for extensive biomarker testing is mandatory before the start of treatment with a targeted agent included in the protocol.

8. Ability to understand and the willingness to sign a written informed consent document and comply to the protocol.

9. For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.

10. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Male patients should avoid impregnating a female partner. Male patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse.

1. Ongoing toxicity > grade 2, other than alopecia or > grade 1 neuropathy.

2. Patient is receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement). Required wash out period prior to starting study treatment is at least two weeks. An exception is made for:

1. Patients suffering from CRPC are allowed to continue androgen deprivation therapy.

2. Medications that are prescribed for supportive care but may potentially have an anti-cancer effect (e.g., megestrol acetate, bisphosphonates). These medications must have been started ≥ 1 week prior to enrollment on this study.

3. Received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant EPO) within 14 days prior to the first dose of study intervention

4. Patient is pregnant or nursing.

6. Patients with clinically significant preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure are not eligible.

7. Patients with clinically significant preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure are not eligible.

8. Patients with known left ventricular ejection fraction (LVEF) < 45% are not eligible

9. Patients with stroke (including TIA) or acute myocardial infarction within 3 months before the first dose of study treatment are not eligible

10. Patients with any other clinically significant medical condition 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 including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Katriina Jalkanen

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katriina Jalkanen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Hospital Comprehensive Cancer Centre

Locations

Turku University Hospital Cancer Centre

Turku, Southwest Finland, Finland

Site Status: RECRUITING

Helsinki University Hospital Comprehensive Cancer Center

Helsinki, Uusimaa, Finland

Site Status: RECRUITING

Kuopio University Hospital

Kuopio, , Finland

Site Status: RECRUITING

Oulu University Hospital OYS Cancer Center

Oulu, , Finland

Site Status: RECRUITING

Tampere University Hospital Department of Oncology

Tampere, , Finland

Site Status: RECRUITING

Countries

Finland

Central Contacts

Tanja Juslin

Role: CONTACT

tanja.juslin@hus.fi

+358405597415

Facility Contacts

Erika Alanne, MD, PhD

Role: primary

Tanja Juslin

Role: primary

Okko Kääriäinen, MD

Role: primary

Sanna Iivanainen, MD. PhD.

Role: primary

Minna Tanner, MD, PhD

Role: primary

Other Identifiers

FINPROVE

Identifier Type: -

Identifier Source: org_study_id