A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

Ведущий спонсор: Bayer

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

The primary objective of this study is to investigate the efficacy of larotrectinib for the treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor kinase (NTRK) of types 1-3 in children and adults. Secondary objectives comprise the efficacy and safety of larotrectinib in different NTRK-tumor types.

• Solid Tumors Harboring NTRK Fusion

Тип вмешательства: Drug

Название вмешательства: BAY2757556 (Larotrectinib, Vitrakvi)

Описание: Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.

Другое имя: LOXO-101

Критерии:

Inclusion Criteria: - Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly-certified laboratories. - Subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy. - Subjects must have at least one measurable lesion as defined by RECIST v1.1. Subjects with solid tumors without RECIST v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to Cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type. Subjects with primary CNS tumors should meet the following criteria 1. Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type. 2. Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice. 3. Imaging study performed within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study. 4. Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment. - Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) ≥50% - Tumor tissue before treatment (mandatory). If neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor. - Willingness of men and women of reproductive potential to use double effective birth control methods, defined as one used by the subject and another by his/her partner, for the duration of treatment and for 1 month following study completion. Exclusion Criteria: - Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (TRK). Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible. - Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.) Subjects with primary central nervous system (CNS) tumors are eligible. - Pregnancy or lactation. - Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures. - Unstable cardiovascular disease is defined as: - In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy. - Myocardial infarction within 3 months of screening. - Stroke within 3 months of screening.

Пол:

All

Минимальный возраст:

18 Years

Максимальный возраст:

N/A

Здоровые волонтеры:

No

Фамилия: Bayer Clinical Trials Contact

Телефон: (+)1-888-84 22937

Argentina

Australia

Belgium

Brazil

Canada

China

Colombia

Czechia

Denmark

France

Germany

Greece

Hungary

India

Ireland

Italy

Japan

Korea, Republic of

Norway

Poland

Portugal

Russian Federation

Singapore

Slovakia

Spain

Sweden

Taiwan

Turkey

Ukraine

United Kingdom

United States

2022-01-01

Тип: Sponsor

• Non-small cell lung cancer
• Thyroid cancer
• Sarcoma
• Colorectal cancer
• Salivary gland cancer
• Biliary cancer
• Central nervous system (CNS) Tumor
• Breast cancer
• Melanoma
• Neurotrophic tyrosine receptor kinase (NTRK)
• NTRK1
• NTRK2
• NTRK3
• Fusion Positive
• TRK fusion
• TRKA
• TRKB
• TRKC
• ETV6

• Neoplasms

Метка: Arm 1_NSCLC

Тип: Experimental

Описание: Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)

Метка: Arm 2_Thyroid

Тип: Experimental

Описание: Patients with solid thyroid tumors harboring NTRK fusions (arm closed)

Метка: Arm 3_Sarcoma

Тип: Experimental

Описание: Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)

Метка: Arm 4_Colorectal

Тип: Experimental

Описание: Patients with solid colorectal tumors harboring NTRK fusions

Метка: Arm 5_Salivary

Тип: Experimental

Описание: Patients with solid salivary tumors harboring NTRK fusions (arm closed)

Метка: Arm 6_Biliary

Тип: Experimental

Описание: Patients with solid biliary tumors harboring NTRK fusions (arm closed)

Метка: Arm 7_Primary CNS

Тип: Experimental

Описание: Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)

Метка: Arm 8_Other tumors

Тип: Experimental

Описание: Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions

Метка: Arm 9_Solid tumors without confirmed NTRK fusion

Тип: Experimental

Описание: Patients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)

Метка: Arm 10- Perspective cohort

Тип: Experimental

Описание: Patients with melanoma, non secretory breast and colorectal cancer harboring NTRK fusions.

Распределение: Non-Randomized

Модель вмешательства: Parallel Assignment

Первичное назначение: Treatment

Маскировка: None (Open Label)