A Study of Alectinib in RET-rearranged Non-small Cell Lung Cancer or RET-mutated Thyroid Cancer

NCT03131206 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-080
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

This research trial is studying a drug called alectinib as a possible treatment for non-small cell lung cancer (NSCLC) with specific genetic alterations known as ALK or RET rearrangements, and thyroid cancer with RET rearrangements.

Conditions

ALK-positive Non-small Cell Lung Cancer (NSCLC); RET-positive Non-small Cell Lung Cancer (NSCLC); RET-positive Thyroid Cancer

Keywords

Non-small cell lung cancer; NSCLC; ALK; RET; alectinib; Thyroid cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (Phase 1)

  The maximally administered dose (MAD) of the study medication will be defined as the dose level where at least two subjects develop toxicities consistent with a DLT definition. In this situation, the dose level immediately below the MAD will be defined as the MTD.

  28 Days

• Objective Response Rate

  Preliminary evaluation of objective response rate (ORR) of alectinib was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Per RECIST v1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  8 weeks

Secondary Outcomes (5)

• Area Under the Plasma Concentration Versus Time Curve (AUC) of Alectinib

  4 months

• Progression Free Survival

  2 Years

• Overall Survival

  OS was calculated at the time of analysis, which was approximately 22 months after the study opened to enrollment.

• Duration of Response

  2 Years

• Peak Plasma Concentration (Cmax) of Alectinib

  4 months

Study Arms (4)

Phase 1 RP2D of alectinib

EXPERIMENTAL

The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have NSCLC, not everyone who participates in this research study will receive the same dose of the study drug. The dosage will depend on the number of participants who have been enrolled in the study and how well the dosage has been tolerated. * Alectinib * Oral, BID * A 7-day lead-in dosing period will be administered at the start of each dose level. Each treatment cycle will be defined as 28 consecutive days.

Drug: Alectinib

Cohort A

EXPERIMENTAL

Participants with RET-rearranged NSCLC with no previous history of RET-TKI therapy. * Alectinib * Oral, BID, participants will receive the RP2D identified during Phase 1. * Each treatment cycle will be defined as 28 consecutive days.

Drug: Alectinib

Cohort B

EXPERIMENTAL

Participants with RET-rearranged NSCLC with previous history of RET-TKI therapy. * Alectinib * Oral, BID, participants will receive the RP2D identified during Phase 1. * Each treatment cycle will be defined as 28 consecutive days.

Drug: Alectinib

Cohort C

EXPERIMENTAL

Participants with RET-rearranged thyroid cancer * Alectinib * Oral, BID, participants will receive the RP2D identified during Phase 1. * Each treatment cycle will be defined as 28 consecutive days.

Drug: Alectinib

Interventions

Alectinib DRUG

* Oral, BID * Phase I: A 7-day lead-in dosing period will be administered at the start of each dose level. Each treatment cycle will be defined as 28 consecutive days. * Phase II: Participants will be treated at the RP2D identified during Phase I. Each treatment cycle will be defined as 28 consecutive days.

Also known as: Alecensa

Cohort A; Cohort B; Cohort C; Phase 1 RP2D of alectinib

Eligibility Criteria

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

You may qualify if:

• Tumor Types:
• Phase 1: Subjects must have a histologically or cytologically confirmed diagnosis of locally advanced (AJCC Stage IIIB) not amenable to curative therapy or metastatic (AJCC Stage IV) NSCLC that carries a RET rearrangement, as determined by fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), or next generation sequencing (NGS) via a CLIA-certified local diagnostic test (LDT).
• \--- OR-
• Phase 1: Subjects must have a histologically or cytologically confirmed diagnosis of metastatic (AJCC Stage IV) NSCLC that carries an ALK rearrangement with CNS metastases, as determined by FISH, RT-PCR, immunohistochemistry (IHC), or NGS via a CLIA-certified LDT.
• Phase 2 Cohorts A\&B: Subjects must have a histologically or cytologically confirmed diagnosis of locally advanced (AJCC Stage IIIB) not amenable to curative therapy or metastatic (AJCC Stage IV) NSCLC that carries a RET rearrangement, as determined by FISH, RT-PCR, or NGS via a CLIA-certified LDT.
• Phase 2 Cohort C (thyroid cancer): Subjects must have a histologically or cytologically confirmed diagnosis of metastatic thyroid cancer (Stage IV) that carries either a RET rearrangement or activating RET mutation, as determined by FISH, RT-PCR, or NGS via a CLIA-certified LDT.
• Disease Status Requirements:
• Phase 1: Subjects with a RET rearrangement must have had disease progression after at least one prior line of systemic therapy. Subjects with an ALK rearrangement may be either treatment naive or may have received prior treatment, and must have CNS disease present at baseline. Subjects cannot have received more than one prior RET TKI (such as, but not limited to, vandetanib, sorafenib, sunitinib, ponatinib, or cabozantinib). Subjects enrolling to the Phase 1 portion of the trial must not have received prior alectinib therapy.
• Phase 2:
• Cohort A: RET-positive NSCLC subjects must have received at least one prior line of therapy, but must be RET TKI-naive.
• Cohort B: RET-positive NSCLC that has previously been treated with one RET TKI. Subjects cannot have received more than one prior RET TKI and must not have received prior alectinib.
• Cohort C: RET-positive thyroid cancer, must be radioactive iodine refractory.
• Subjects must have at least one measurable target lesion according to RECIST v1.1.
• Subjects enrolling to the phase 1 portion of the trial who have received a prior RET TKI must be able and willing to undergo a pre-treatment fresh tumor biopsy.
• Subjects enrolling to Cohort B or C of the phase 2 portion of the trial who have received a prior RET TKI must be able and willing to undergo a pre-treatment fresh tumor biopsy.

You may not qualify if:

• Cytotoxic chemotherapy or immunotherapy within 3 weeks of study entry.
• Oral targeted therapy within 5 half-lives (if known) or 3 weeks (if half-life is unknown) of study entry.
• Phase 1: subjects who have received prior alectinib therapy.
• For enrollment to the phase 1 portion of the trial: Administration of any cytochrome P450 (CYP)3A inhibitors or inducers within 14 days prior to the first dose of alectinib and from Cycle 1 Day 1 - Cycle 2 Day 8 of the phase 1 portion of the trial. Following completion of this period, strong/potent cytochrome P450 (CYP)3A inhibitors or inducers are prohibited while on study. Please see APPENDIX C.
• Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
• Major surgery within 4 weeks of study entry. Minor surgical procedures (e.g., port insertion) are not excluded, but sufficient time should have passed for wound healing (as determined by the treating investigator).
• Subjects who are receiving any other investigational agents.
• Liver disease characterized by:
• \-- ALT or AST \> 3 × institutional ULN (≥ 5 × ULN for subjects with concurrent liver metastasis) confirmed on two consecutive measurements
• \--- OR-
• Absolute impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices
• \--- OR-
• Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices
• OR-
• Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genentech, Inc.: collaborator

Study Sites (4)

University of California, Irvine

Irvine, California, 92697-7600, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms

Interventions

alectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Mark Awad, MD, PhD
• Organization: Dana-Farber Cancer Institute

mark_awad@dfci.harvard.edu

6176323468

Study Officials

• Mark Awad, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 19, 2017
• First Posted: April 27, 2017
• Study Start: June 19, 2017
• Primary Completion: November 8, 2018
• Study Completion: April 8, 2019
• Last Updated: September 27, 2021
• Results First Posted: November 25, 2019

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)