A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC). (AcceleRET-MTC)

January 4, 2024 updated by: Hoffmann-La Roche

A Phase III, Randomized, Open-Label Study of Pralsetinib Versus Standard of Care for Treatment of RET-Mutated Medullary Thyroid Cancer.

A study to evaluate the efficacy and safety of pralsetinib compared with SOC treatment (cabozantinib or vandetanib) for participants with RET (rearranged during transfection)-mutant MTC who have not previously received a SOC MultiKinase Inhibitor (MKI) therapy. Participants will be randomized in a 1:1 ratio into one of two treatment arms: Arm A (pralsetinib) or Arm B (investigator's choice of either cabozantinib or vandetanib for adults and vandetanib for adolescents). Participants whose disease progresses during SOC treatment will be offered the option to cross over to receive pralsetinib after confirmation of progressive disease by blinded independent central review (BICR).

Study Overview

Status

Status

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Withdrawn

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.

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.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Spain
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocío

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

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Must have histologically confirmed unresectable locally advanced or metastatic MTC and be a candidate for systemic therapy with SOC MKI.
  • Must have received no prior systemic anticancer treatment with MKI therapies for advanced or metastatic MTC.

  • Must have radiologically confirmed progressive disease within the last 14 months and at least one of the following:

    1. A MTC-associated symptom and
    2. CLN (Calcitonin) and CEA (carcinoembryonic antigen) level doubling time of less than 24 months.
  • Confirmed RET mutation.
  • Must be able to swallow an oral medication.
  • Must have an ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-2.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use appropriate contraception during the treatment period and for the respective period of time after final dose of study drug.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use appropriate contraception during the treatment period and for the respective period of time after final dose of study drug and to refrain from donating sperm.

Exclusion Criteria:

  • Participants who are pregnant or breastfeeding, or intending to become pregnant during the study within 14 days after the final dose of pralsetinib or within 4 months after the final dose of vandetanib or cabozantinib.
  • Have disease that is suitable for surgery or radiotherapy administered with curative intent.
  • Have been previously treated with any systemic kinase inhibitor therapy regimens, including a selective RET inhibitor, given for recurrent and/or metastatic disease.
  • Have received any radiation therapy within 14 days prior to Day 1 of Cycle 1 and any related toxicity must be resolved to Grade 1 or better.
  • Participant's tumor has any additional known primary driver alterations other than RET.
  • Have known hypersensitivity to pralsetinib, vandetanib, or cabozantinib, or any of their ingredients.
  • Have a history of pneumonitis of non-infectious etiology within the last 12 months.
  • Have ongoing treatment with chronic immunosuppressants or systemic steroids >10 mg/day.
  • Have any history of hereditary bleeding disorder or any evidence of hematemesis.
  • Have had major surgery or invasive dental procedure within 3 weeks prior to Day 1 of Cycle 1.
  • Have central nervous system (CNS) metastases that are associated with progressive neurologic symptoms, untreated spinal cord compression or requires increasing doses of corticosteroids to control the CNS disease.
  • Have clinically significant, uncontrolled, cardiovascular disease.
  • Have required treatment with a prohibited medication or herbal remedy.
  • Have received hematopoietic growth factor support or transfusion within 14 days of the first dose of study drug.
  • Had a major surgical procedure within 14 days of the first dose of study drug.
  • Have a history of another primary malignancy that has been diagnosed or required therapy within the past 2 years before randomisation.
  • Have a serious infection requiring intravenous (IV) antibiotics within 7 days prior to initiation of study treatment.
  • Have an active, uncontrolled infection (viral, bacterial, or fungal) or is positive for Hepatitis B/C infections (HBV/HCV) or HIV.
  • Have received organ or allogenic bone marrow or peripheral blood stem cell transplant.
  • Is a female who is unwilling to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 4 months after the last dose of study drug.
  • Is a male who is unwilling to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 120 days after the final dose of study drug.
  • Have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's or Sponsor's opinion, could affect the safety of the patient or impair the assessment of study results.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
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.
Experimental: Arm A (Pralsetinib)
Participants will receive pralsetinib at a dose of 400 milligrams (mg) orally once daily (PO QD) in 28-day cycles.
Drug: Pralsetinib
Participants will receive pralsetinib at a dose of 400 mg, as per the dosing schedule described above.
Active Comparator: Arm B (SOC: Cabozantinib/Vandetanib)
Adult participants will receive investigator's choice of SOC MKI therapy with either 140 mg cabozantinib PO QD or 300 mg vandetanib PO QD in 28-day cycles. Adolescents participants (≥ 12 and < 18 years of age) will receive vandetanib, PO QD or every other day, in 28-day cycles depending on the body surface area (BSA), at a dose determined according to the dosing nomogram available in the E.U. Vandetanib SmPC.
Drug: Cabozantinib
Adult participants will receive cabozantinib at a dose of 140 mg, as per the dosing schedule described above.
Drug: Vandetanib
Adult participants will receive vandetanib at a dose of 300 mg and adolescent participants will receive vandetanib as per the dosing schedule described above.

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
Progression-Free Survival (PFS)
Time Frame: Up to 5 years
Defined as the time from randomization date to the first documented PD (Progression of Disease), as assessed by BICR according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or death due to any cause, whichever occurs first.
Up to 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time-To-Treatment Failure (TTF)
Time Frame: Up to 13 years
Defined as the time from randomization date to the discontinuation of study drug during the treatment period due to death, treatment-related adverse event, or PD, as assessed by BICR according to RECIST v1.1, whichever occurs first.
Up to 13 years
Objective Response Rate (ORR)
Time Frame: Up to 13 years
Defined as the proportion of participants who achieve a CR (Complete Response) or a PR (Partial Response) prior to progressive disease and/or other anti-cancer therapy, as assessed by BICR according to RECIST v1.1.
Up to 13 years
Overall Survival (OS)
Time Frame: Up to 13 years
Defined as the time from randomization date to death due to any cause.
Up to 13 years
Percentage of Participants With Adverse Events (AEs)
Time Frame: Up to 13 years
Incidence and severity determined according to the NCI CTCAE v5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0) criteria.
Up to 13 years
Duration of Response (DOR)
Time Frame: Up to 13 years
Defined as the number of weeks from the time criteria are first met for either a CR or a PR, until the date of documented PD, as assessed by BICR according to RECIST v1.1, or death due to any cause, whichever occurs first.
Up to 13 years
Disease Control Rate (DCR)
Time Frame: Up to 13 years
Defined as the proportion of participants who experience a best response of CR, PR, or stable disease, as assessed by BICR according to RECIST v1.1.
Up to 13 years
Clinical Benefit Rate (CBR)
Time Frame: Up to 13 years
Defined as the proportion of participants who experience a CR or a PR or a best response of stable disease with a minimum duration of 6 months, as assessed by BICR according to RECIST v1.1.
Up to 13 years
Time to Deterioration of Function
Time Frame: Up to 13 years
Defined as the time from randomization to the date of a participant's first >= 10-point decrease from baseline score, as assessed through the use of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Up to 13 years
Quality of Life (QoL)
Time Frame: Up to 13 years
Defined as the time from randomization to the date of a participant's first >= 10-point decrease from baseline score, as assessed through the use of the GHS (Global Health Status)/QoL scales.
Up to 13 years
Acceptability and Palatability of Pralsetinib Capsules
Time Frame: Up to 13 years
Acceptability Survey scores on Day 1 of Cycle 1 and Crossover Cycle 1 (each cycle is 28 days).
Up to 13 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.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

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 (Estimated)

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.
November 30, 2023

Primary Completion (Estimated)

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 6, 2027

Study Completion (Estimated)

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.
April 12, 2035

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).
February 17, 2021

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.
February 17, 2021

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.
February 18, 2021

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.
January 5, 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.
January 4, 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.
January 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.
  • CO42865
  • 2020-005269-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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