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

NCT04760288 | Withdrawn Phase 3 FDA Drug

• 2 other identifiers: CO428652020-005269-15
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Medullary Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  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 Outcomes (10)

• Time-To-Treatment Failure (TTF)

  Up to 13 years

• Objective Response Rate (ORR)

  Up to 13 years

• Overall Survival (OS)

  Up to 13 years

• Percentage of Participants With Adverse Events (AEs)

  Up to 13 years

• Duration of Response (DOR)

  Up to 13 years

Study Arms (2)

Arm A (Pralsetinib)

EXPERIMENTAL

Participants will receive pralsetinib at a dose of 400 milligrams (mg) orally once daily (PO QD) in 28-day cycles.

Drug: Pralsetinib

Arm B (SOC: Cabozantinib/Vandetanib)

ACTIVE COMPARATOR

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; Drug: Vandetanib

Interventions

Pralsetinib DRUG

Participants will receive pralsetinib at a dose of 400 mg, as per the dosing schedule described above.

Arm A (Pralsetinib)

Cabozantinib DRUG

Adult participants will receive cabozantinib at a dose of 140 mg, as per the dosing schedule described above.

Arm B (SOC: Cabozantinib/Vandetanib)

Vandetanib DRUG

Adult participants will receive vandetanib at a dose of 300 mg and adolescent participants will receive vandetanib as per the dosing schedule described above.

Arm B (SOC: Cabozantinib/Vandetanib)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• A MTC-associated symptom and
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Carcinoma, Medullary

Interventions

pralsetinib; cabozantinib; vandetanib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 18, 2021
• Study Start: November 30, 2023
• Primary Completion (Estimated): October 6, 2027
• Study Completion (Estimated): April 12, 2035
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

ES (1)