Brain Neoplasms, Bronchial Neoplasms, Carcinoma, Bronchogenic, Central Nervous System, Cholangiocarcinoma, Colonic Diseases, Colorectal Neoplasms, Digestive System Diseases, Digestive System Neoplasms, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Head and Neck Neoplasms, Intestinal Diseases, Intestinal Neoplasms, Lymphoma, Large-Cell, Anaplastic, Melanoma, Neoplasms, Neoplasms by Site, Neuroendocrine Tumors, Ovarian Neoplasms, Pancreatic Neoplasms, Respiratory Tract Diseases, Respiratory Tract Neoplasms, Salivary Gland Neoplasms, Sarcoma, Thoracic Neoplasms, Thyroid Cancer, Papillary, Thyroid Neoplasms
Conditions
Keywords
agnostic, ALK+, Alk-positive, ALK positive, ALK mutation, GI, breast, sarcoma, neuroendocrine, female reproductive, ALK, ALK fusions, ALK gene rearrangements, colorectal cancer, entrectinib, basket study, salivary gland cancers, primary brain tumors, melanoma, sarcomas, papillary thyroid cancer, renal cell cancer, pancreatic cancer, breast cancer, cholangiocarcinoma, head & neck cancers, ovarian cancer, anaplastic lymphoma kinase positive, solid tumors, ALK+ solid tumors
Brief summary
This study will evaluate the efficacy and safety of alectinib in participants with Anaplastic Lymphoma Kinase (ALK)-positive locally advanced or metastatic solid tumors other than lung cancer.
Interventions
DRUGAlectinib
Participants will receive 600 mg oral alectinib BID until disease progression, unacceptable toxicity, withdrawal from treatment, or death.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed ALK-positive locally-advanced or metastatic solid tumor excluding lung cancer * ALK-positive tumor as per Foundation Medicine, Inc (FMI) next-generation sequencing (NGS) (NGS F1CDx, F1LCDx, or F1HEME) or per local accredited laboratory using validated NGS testing of tumor tissue or peripheral blood * No alternative effective standard therapy available, or standard therapy considered unsuitable or intolerable to the participant * Other cancer therapies are allowed, including investigational drugs, if any treatment-related toxicities (excluding alopecia) have resolved to grade \</= 1 or to laboratory values as defined by the protocol * Measurable disease at baseline as assessed by the Investigator per RECIST v1.1 or RANO criteria (for participants with primary CNS tumors) * Life expectancy of at least 12 weeks * Eastern cooperative oncology group (ECOG) performance status of 0-2 * Adequate hemataologic, hepatic, and renal function * Participants with primary central nervous system (CNS) tumors are available * Participants with brain or leptomeningeal metastasis are allowed in the study if asymptomatic and if they meet additional criteria as defined by the protocol * Willingness to comply with study procedures * Willingness to comply with home-base approach and visits by Mobile Nurses * Ability to swallow alectinib capsules intact * Women of childbearing potential must test negative for pregnancy at screening and prior to the first dose of study drug * Women of childbearing potential must agree to remain abstinent or use contraceptive methods as defined by the protocol and refrain from donating eggs during the treatment period and for at least 90 days after the last dose of alectinib * Men must agree to remain abstinent or use contraceptive methods as defined by the protocol and refrain from donating sperm during the treatment period and for at least 90 days after the last dose of alectinib
Exclusion criteria
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of alectinib * Lung Cancer * Patients with one of the following ALK point mutations: I1171X, G1202R, V1180L * Prior therapy with an ALK inhibitor * Liver disease as described in the protocol * Known HIV, hepatitis B, or hepatitis C (HCV) infection * Patients with symptomatic bradycardia * Patients with symptomatic or unstable brain metastasis; patients with primary CNS tumors are allowed * Malabsorption syndrome or any other condition that would interfere with enteral absorption * Incomplete recovery from any surgery prior to treatment * Any other malignancies within 5 years prior to enrollment, except for those described in the protocol * Any serious medical condition or abnormality in clinical laboratory tests that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study * History of hypersensitivity to any of the ingredients in the alectinib drug formulation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Confirmed Objective Response Rate (ORR) as Determined by the Investigator Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Approximately 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DOR) as Determined by Both the Investigator and by BICR Per RECIST v1.1 | From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years) |
| Progression-Free Survival (PFS) as Determined by Both the Investigator and by BICR Per RECIST v1.1 | From first dose of alectinib to disease progression or death from any cause, whichever occurs first (up to 5 years) |
| Central Nervous System (CNS) ORR by BICR Per RECIST v1.1 | Baseline up to 5 years |
| CNS DOR by BICR Per RECIST v1.1 | From the first observation of CNS response to the first observation of CNS progression or death from any cause (up to 5 years) |
| Overall Survival (OS) | From the first dose of study drug to death from any cause (up to 5 years) |
| Percentage of Participants With Adverse Events (AEs) | Approximately 1 year |
| Confirmed ORR as Determined by Blinded Independent Center Review (BICR) Per RECIST v1.1 | 0 days |
| Plasma Concentration of Alectinib | Baseline up to 5 years |
| ORR in Participants With Primary CNS Tumors as Determined by Both BICR and the Investigator Per Response Assessment in Neuro-Oncology (RANO) Criteria | Up to 5 years |
| DOR in Participants With Primary CNS Tumors as Determined by Both BICR and the Investigator Per RANO Criteria | From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years) |
| PFS in Participants With Primary CNS Tumors as Determined by Both BICR and the Investigator Per RANO Criteria | From first dose of alectinib to disease progression or death from any cause, whichever occurs first (up to 5 years) |
| OS in Participants With Primary CNS Tumors | From the first dose of study drug to death from any cause (up to 5 years) |
| Percentage of Participants With Serious Adverse Events (SAEs) | Approximately 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALK-positive Solid Tumors Participants with locally advanced or metastatic ALK-positive tumors were to receive alectinib twice daily (BID) until disease progression, unacceptable toxicity, death, or withdrawal from the study for any reason. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Subject withdrawal of consent | 1 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | — Years |
| Race/Ethnicity, Customized | — Participants |
| Sex/Gender, Customized | — Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Confirmed Objective Response Rate (ORR) as Determined by the Investigator Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time frame: Approximately 1 year
Population: Confirmed ORR was defined as the proportion of participants with a complete or partial response (CR or PR) confirmed at least 28 days after initial response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALK-positive Solid Tumors | Confirmed Objective Response Rate (ORR) as Determined by the Investigator Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | 0 Percentage |
Secondary
Central Nervous System (CNS) ORR by BICR Per RECIST v1.1
Time frame: Baseline up to 5 years
Population: CNS ORR was defined as the objective tumor response rate (CR or PR) of CNS lesions and could not be calculated due to an insufficient number of participants with the event.
Secondary
CNS DOR by BICR Per RECIST v1.1
Time frame: From the first observation of CNS response to the first observation of CNS progression or death from any cause (up to 5 years)
Population: CNS DOR was defined as the time from the first observation of CNS response until the first observation of CNS progression or death from any cause and could not be calculated due to an insufficient number of participants with the event.
Secondary
Confirmed ORR as Determined by Blinded Independent Center Review (BICR) Per RECIST v1.1
Time frame: 0 days
Population: BICR was not performed.
Secondary
DOR in Participants With Primary CNS Tumors as Determined by Both BICR and the Investigator Per RANO Criteria
Time frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years)
Population: DOR was defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause and could not be calculated due to an insufficient number of participants with the event.
Secondary
Duration of Response (DOR) as Determined by Both the Investigator and by BICR Per RECIST v1.1
Time frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years)
Population: DOR was defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause and could not be calculated due to an insufficient number of participants with the event.
Secondary
ORR in Participants With Primary CNS Tumors as Determined by Both BICR and the Investigator Per Response Assessment in Neuro-Oncology (RANO) Criteria
Time frame: Up to 5 years
Population: CNS ORR was defined as the objective tumor response rate (CR or PR) of CNS lesions and could not be calculated due to an insufficient number of participants with the event.
Secondary
OS in Participants With Primary CNS Tumors
Time frame: From the first dose of study drug to death from any cause (up to 5 years)
Population: OS was defined as the time from first dose of study drug to death from any cause- and could not be calculated due to an insufficient number of participants with the event.
Secondary
Overall Survival (OS)
Time frame: From the first dose of study drug to death from any cause (up to 5 years)
Population: OS was defined as the time from first dose of study drug to death from any cause- and could not be calculated due to an insufficient number of participants with the event.
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: Approximately 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALK-positive Solid Tumors | Percentage of Participants With Adverse Events (AEs) | 100 Percentage |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs)
Time frame: Approximately 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALK-positive Solid Tumors | Percentage of Participants With Serious Adverse Events (SAEs) | 100 Percentage |
Secondary
PFS in Participants With Primary CNS Tumors as Determined by Both BICR and the Investigator Per RANO Criteria
Time frame: From first dose of alectinib to disease progression or death from any cause, whichever occurs first (up to 5 years)
Population: PFS was defined as the time from the first dose of alectinib to disease progression or death from any cause and could not be calculated due to an insufficient number of participants with the event.
Secondary
Plasma Concentration of Alectinib
Time frame: Baseline up to 5 years
Population: Plasma concentration data was not collected as the data for one participant was not sufficient.
Secondary
Progression-Free Survival (PFS) as Determined by Both the Investigator and by BICR Per RECIST v1.1
Time frame: From first dose of alectinib to disease progression or death from any cause, whichever occurs first (up to 5 years)
Population: PFS was defined as the time from the first dose of alectinib to disease progression or death from any cause and could not be calculated due to an insufficient number of participants with the event.