Alectinib-induced Endocrine Toxicity (TOSS-ALK)

March 25, 2024 updated by: Bria Emilio, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Alectinib-induced Endocrine Toxicity in Patients With ALK-positive Advanced NSCLC: an Onservational Study

The experimental Cohort A (male ALK+ ANSCLC patients receiving alectinib), the control Cohort B (female ALK+ ANSCLC patients receiving alectinib) and control Cohort C (male NON-ALK ANSCLC patients) were prospectively evaluated for full hormone assessment of androgen deficiency, AT 8 weeks after treatment start and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to endocrinologist.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Male patients (Cohorts A-C). After 8 weeks from treatment start (T1), as the same time of initial endocrine evaluation, we assessed symptoms of androgen deficiency by using the Androgen Deficiency in Aging Males (ADAM) questionnaire (Supplementary, SD1), a validated screening assessment of hypogonadism in adult males [15]. Next, the questionnaire was collected every 12 weeks during the routine clinic visits up to three years (if considered clinically appropriated). The response to the questionnaire was considered consistent with possible hypogonadism (i.e. positive), if the patient reported at least one major symptom (loss of libido and/or impotence; questions 1 and 7) or at least three minor symptoms. In case of suspected hypogonadism at ADAM questionnaire, hormonal tests were again performed and the patient was referred to Andrology Unit of the Endocrinology Departement in case of abnormal results. Andrology visit included physical examination, testicular and scrotum ultrasound, medical history and hormonal tests reviewing; when testosterone replacement and/or drugs for erectile dysfunction were prescribed, the overall effectiveness on symptoms of hypogonadism (improved/not improved) was assessed by the andrologist and checked at next oncologic visits.

Female patients (Cohort B). After 8 weeks from treatment start (T1), as the same time of initial endocrine assessment, we assessed symptoms of sexual dysfunctions, according to menopausal status, by using the EORTC QLQ - BR23 and FACT-B (Version 4) questionnaires. In case of clinically significant gynaecological symptoms and/or abnormal results of sexual hormones axis in relation to menopausal status, the patients were referred to multidisciplinary evaluation by an endocrinologist and a gynaecologist. Multidisciplinary evaluation included physical and gynaecological examination, pelvic ultrasound, medical history and hormonal tests reviewing; diagnosis and treatment of endocrine/gynaecological dysfunction and prescribed treatment/intervention were reported in medical history and checked at next oncologic visits

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
98

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00168
        • Fondazione Policlinico Gemelli IRCCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

TOSS-ALK is single-Institution observational prospective sex-based trial aimed to assess endocrine toxicity in ALK+ advanced/metastatic ANSCLC male patients treated with first-line alectinib (Cohort A). As control cohorts, we included female ALK+ ANSCLC patients (Cohort B) and male patients with NON-ALK+ NSCLC who are receiving active treatment (ACT) according to tumour molecular profiling (Cohort C).

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed advanced NSCLC (ANSCLC) For ALK+ NSCLC (Cohorts A-B) 1a. ALK-rearrangement confirmed by NGS and/or VENTANA ALK (D5F3) immunoistochemical assay 1b. Treatment naïve patients candidate to treatment with alectinib oral at standard dose of 600 mg twice daily
  2. Patient aged 18 to 70 years
  3. To be sexually active at time of enrolment
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  5. Written informed consent

Exclusion Criteria:

  1. History of endocrine disorders, excepting for controlled hypothyroidism (surgical or non-surgical) treated with replacement levothyroxine since at least 2 years
  2. Any cancer-related or medical condition that would interfere with the patient reported outcomes or laboratory assessment. Examples include, but are not limited to:

2a. Cancer-related conditions that may preclude/undermine sexual activity (e.g. leptomeningeal carcinomatosis, pathological vertebral fractures, gonadic metastases, unstable spinal cord compression, uncontrolled neurological symptoms, surgical complications)

2b. History of chronic liver disease or hormonal replacement therapy (e.g. ADT for prostatic cancer)

2c. Participants who not adequately recovered from previous confirmed chemotherapy-induced gonadotoxicity (e.g. cisplatin)

2d. Chronic use of drugs with known effect on male sexuality, including opiates, anxiolytics, antidepressants, mood stabilizers, beta blockers (e.g. atenolol) and high dose diuretics

2e. Psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

2f. Major psychological disorder and/or high distress level that would interfere with sexual function and the participant's ability to cooperate with the requirements of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Cohort A
Male ALK-positive ANSCLC patients receiving first-line treatment with alectinib
Drug: Alectinib 150 MG [Alecensa]
First line treatment for cohorts A and B
Other Names:
  • Alecensa
Cohort B
Female ALK-positive ANSCLC patients receiving first-line treatment with alectinib
Drug: Alectinib 150 MG [Alecensa]
First line treatment for cohorts A and B
Other Names:
  • Alecensa
Cohort C
Male ALK-negative ANSCLC patients receiving first-line treatment according to molecular profiling

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of endocrine toxicity in overall ALK-positive
Time Frame: Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Percentege of endocrine alterations among patients included in Cohort A and B
Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Incidence of symptomatic hypogonadism in male ANSCLC patients
Time Frame: Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Percentage of endocrine alterations and/or clinical sexual dysfuctions among male patients included in Cohort A and C
Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 12, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 25, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4806

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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