Trametinib in Patients With Advanced Neurofibromatosis Type 1 (NF1)-Mutant Non-small Cell Lung Cancer

NCT03232892 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 166521NCI-2017-02295
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II trial to evaluate trametinib in patients with locally advanced non-squamous, non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with progressive disease on at least one prior line of therapy.

Conditions

Non-small Cell Lung Cancer

Keywords

NSCLC; NF-1 mutant

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  For participants receiving at least one dose of study treatment, the ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence as assessed over a 1-year period from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined. We will test the hypothesis that the ORR is greater than the null hypothesis of 10% using the Fisher's exact test.

  Up to 1 year

Secondary Outcomes (4)

• Duration of Response (DR)

  Up to 4 years

• Disease Control Rate (DCR) According to RECIST Version 1.1 Criteria.

  Up to 4 years

• Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria.

  Up to 1 year

• Overall Survival (OS)

  Up to 1 year

Study Arms (1)

Trametinib 2.0mg PO daily

EXPERIMENTAL

Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.

Drug: Trametinib

Interventions

Trametinib DRUG

Trametinib 2mg, once daily, PO, 28-day cycles

Also known as: Mekinist

Trametinib 2.0mg PO daily

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed metastatic or unresectable locally advanced, non-squamous, NSCLC.
• Documented non-synonymous somatic mutation in NF1 in any tumor specimen or cell-free DNA assay by Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.
• Received at least one prior line of cancer therapy for the treatment of NSCLC; this should include at least one of the following: platinum (carboplatin or cisplatin) doublet chemotherapy (acceptable combinations include: paclitaxel, docetaxel, abraxane, pemetrexed, gemcitabine, vinorelbine, or etoposide), anti-PD1/PDL1 therapy (pembrolizumab, nivolumab, or atezolizumab), or appropriate targeted therapy in patients with activating EGFR (osimertinib, erlotinib, gefitinib, or afatinib), ALK (alectinib, crizotinib, ceritinib, brigatinib, or loralatinib), or ROS-1 (crizotininb or entrectinib) alterations; therapy may be given as monotherapy or in combination with other cancer therapy (e.g. bevacizumab, ipilumimab)
• Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). Patients whose tumors were found to have an EGFR T790M mutation must also have progressed or been intolerable to treatment with osimertinib.
• Patients with a known Anaplastic lymphoma kinase (ALK)-rearrangement must have progressed or been intolerant to treatment with at least one ALK TKI: crizotinib ceritinib, alectinib,brigatinib, or loralatinib
• Patients with a known ROS-1-rearrangement must have progressed or been intolerant to treatment with crizotinib or entrectinib
• Patients with PDL1 level of \>= 50%, who do not have an ALK-rearrangement or EGFR-mutation, must have progressed or been intolerant to treatment with anti-PD1/PDL1 therapy (pembrolizumab, nivolumab, or atezolizumab)
• Documented disease progression or intolerance to treatment either during or after treatment with most recent therapy.
• Willingness to undergo research biopsy.
• Measurable disease defined by RECIST 1.1 criteria.
• Life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Age ≥ 18 years.
• Resolution of all acute toxic effects of prior chemotherapy, immunotherapy, radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 grade 1.
• Adequate baseline organ function defined as follows:

You may not qualify if:

• Known mutation in KRAS at position G12, G13, or Q61.
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases are allowed as long as they are stable for at least 28 days post-treatment.
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with trametinib . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with trametinib, breastfeeding should be discontinued if the mother is treated with trametinib.
• History of another malignancy. Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer and/or subjects with indolent second malignancies are eligible.
• Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• The subject has received cytotoxic chemotherapy, molecular targeted therapy, or immunotherapy within 21 days before the first dose of study drug (trametinib).
• Prior treatment with MEK inhibitor.
• History of interstitial lung disease or pneumonitis.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
• Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to study enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to study enrollment.
• History of retinal vein occlusion (RVO).
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV infection will be permitted).
• History or evidence of cardiovascular risk including any of the following:
• LVEF \< LLN
• A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec;

Sponsors & Collaborators

• University of California, San Francisco: lead
• Novartis Pharmaceuticals: collaborator
• American Cancer Society, Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

trametinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

There was only one participant enrolled on this trial and the study was terminated early due to low accrual. No analyses were conducted on any of the samples collected as there was insufficient material available for analysis

Results Point of Contact

• Title: Dr. Collin Blakely, MD PhD.
• Organization: University of California, San Francisco

Collin.Blakely@ucsf.edu

(415) 502-6959

Study Officials

• Collin Blakely, MD, PhD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, single-arm, open label, multicenter clinical trial.

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 28, 2017
• Study Start: February 13, 2018
• Primary Completion: September 11, 2019
• Study Completion: September 11, 2019
• Last Updated: December 3, 2019
• Results First Posted: December 3, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)