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AzTrials

Relapsed Metastatic KRAS-Mutated Non-Small Cell Lung CancerPhase 1NCT02258607

Efficacy and Safety of Momelotinib Combined With Trametinib in Adults With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase

A Phase 1 study testing Momelotinib (MMB) and Trametinib in people with Relapsed Metastatic KRAS-Mutated Non-Small Cell Lung Cancer, run by Sierra Oncology LLC - a GSK company at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined with trametinib. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Momelotinib (MMB) and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
5 sitesUnited States
Study dates
11 Mar 2015to 27 Feb 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Individuals with KRAS-mutated metastatic or recurrent non-small cell lung cancer
  • Radiologic documentation of disease progression
  • Measurable disease per RECIST v1.1
  • Adequate organ function defined as follows:
  • Hepatic: Total conjugated bilirubin ≤ 1.25 x upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN) or < 5 x ULN in the setting of liver metastases
  • Hematological: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelet ≥ 100 x 10^9/L, hemoglobin ≥ 9 g/dL
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  • Renal: Serum creatinine < 1.5 x ULN OR calculated creatinine clearance (CLcr) ≥ 60 ml/min
  • Adequate left ventricular ejection fraction (LVEF) ≥ 50%
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Negative serum pregnancy test for females

Who cannot join

  • Less than or equal to 3 weeks since receiving treatment with biologic, small molecule, chemotherapy or other agent for non-small cell lung cancer and 28 days since any prior immunotherapy (such as nivolumab)
  • History of a concurrent or second malignancy, except for specified exceptions in the protocol or any other cancer that has been in complete remission for ≥ 5 years
  • Known positive status for human immunodeficiency virus (HIV)
  • Chronic active or acute viral hepatitis A, B, or C infection or hepatitis B or C carrier
  • Presence of ≥ Grade 2 peripheral neuropathy
  • Brain metastases, or spinal cord compression. Individuals with brain metastases are allowed if they have been treated with irradiation or surgery, are clinically stable without steroid treatment. Individuals with documented leptomeningeal disease are not eligible
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  • A history of uveitis and/or scleritis
  • Retinal pathology beyond normal age-related processes
  • Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal vein occlusion
  • History of newly diagnosed or uncontrolled glaucoma/intraocular pressure > 21 mm Hg as measured by tonography
  • Use of daily and/or chronic oral or ocular steroids. Individuals must be off daily steroids for at least 3 weeks prior to enrolling into the trial
  • History of interstitial pneumonitis
  • History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 480 ms for males and females)
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Study site

    Boston, Massachusetts

  • Study site

    Duarte, California

  • Study site

    Fairfax, Virginia

  • Study site

    Sacramento, California

  • Study site

    Spokane, Washington

Other trials in United States

About this study

Official title: A Phase 1b With Expansion Study Evaluating the Efficacy and Safety of Momelotinib Combined With Trametinib in Subjects With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase

This study is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined with trametinib. Once the MTD of momelotinib (MMB) is determined, the study will proceed to the Dose-finding Lead-in Phase, Part B, to determine the MTD of trametinib. After the MTD is established, the study may proceed to an expansion phase to determine the efficacy, safety, and tolerability of MMB combined with trametinib at the MTD in participants with kirsten rat sarcoma viral oncogene homolog (KRAS) mutated metastatic non-small cell lung cancer (NSCLC). Each treatment cycle will consist of 28 days and treatment will continue in the absence of disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of treatment.

Being tested
Momelotinib (MMB), Trametinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Momelotinib (MMB)Drug

    Also called GS-0387, CYT387

    Momelotinib (MMB) tablet(s) administered orally once or twice daily

  • TrametinibDrug

    Trametinib tablet administered orally once daily

Study groups in NCT02258607
Study groupRoleWhat they receive
Momelotinib (MMB) dose escalationExperimentalParticipants will receive momelotinib (MMB) plus trametinib. Momelotinib (MMB) dose will increase to find the MTD.
Receives: Drug: Momelotinib (MMB); Drug: Trametinib
Trametinib dose escalationExperimentalParticipants will receive momelotinib (MMB) plus trametinib. Trametinib dose will increase to find the MTD.
Receives: Drug: Momelotinib (MMB); Drug: Trametinib
Momelotinib (MMB)+trametinibExperimentalExpansion Phase: participants will receive momelotinib (MMB) plus trametinib for the duration of the study.
Receives: Drug: Momelotinib (MMB); Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)

    Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.

    Measured: Up to 28 days

  2. For Expansion Phase, disease control rate (DCR) at Week 8

    Disease control rate (DCR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumor (RECIST) v1.1.

    Measured: Week 8

Secondary outcomes (8)

  1. For the Dose-finding Lead-in Phase, disease control rate (DCR) at Week 8

    Measured: Week 8

  2. For the Dose-finding Lead-in Phase, overall survival

    Overall survival is defined as the interval from first dose of study drug to death from any cause.

    Measured: Up to 2 years

  3. For the Dose-finding Lead-in Phase, progression free survival (PFS)

    Progression free survival (PFS) is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.

    Measured: Up to 2 years

  4. For the Dose-finding Lead-in Phase, overall response rate (ORR)

    Overall response rate (ORR) is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.

    Measured: Up to 2 years

  5. For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of momelotinib (MMB) and major metabolite GS-644603 as measured by Cmax and AUCtau

    This composite endpoint will measure the plasma PK profile of momelotinib (MMB) and GS-644603. The following parameters will be measured:

    • Cmax: maximum observed concentration of drug in plasma
    • AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)

    Measured: Days 1 and 15 (Cycle 1 only)

  6. For Expansion Phase, overall survival

    Measured: Up to 2 years

  7. For Expansion Phase, progression free survival (PFS)

    Measured: Up to 2 years

  8. For Expansion Phase, overall response rate (ORR)

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2014 (estimated)
  2. Study start11 Mar 2015
  3. Primary completion19 Jul 2016
  4. Study completion27 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02258607
Sponsor's protocol ID
GS-US-370-1297
Status last verified
Jan 2019
First submitted
3 Oct 2014
Last updated
1 Feb 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Barbie DA, Spira A, Kelly K, Humeniuk R, Kawashima J, Kong S, Koczywas M. Phase 1B Study of Momelotinib Combined With Trametinib in Metastatic, Kirsten Rat Sarcoma Viral Oncogene Homolog-Mutated Non-Small-Cell Lung Cancer After Platinum-Based Chemotherapy Treatment Failure. Clin Lung Cancer. 2018 Nov;19(6):e853-e859. doi: 10.1016/j.cllc.2018.07.004. Epub 2018 Aug 4.

    PubMed 30087028

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Momelotinib (MMB) and Trametinib in people with Relapsed Metastatic KRAS-Mutated Non-Small Cell Lung Cancer, run by Sierra Oncology LLC - a GSK company at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02258607, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.

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