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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02857270




Registration number
NCT02857270
Ethics application status
Date submitted
3/08/2016
Date registered
5/08/2016

Titles & IDs
Public title
A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer
Scientific title
A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination With Other Agents in Advanced Cancer
Secondary ID [1] 0 0
I8S-MC-JUAB
Secondary ID [2] 0 0
16419
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Metastatic Melanoma 0 0
Metastatic Non-small Cell Lung Cancer 0 0
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY3214996
Treatment: Drugs - Midazolam
Treatment: Drugs - Abemaciclib
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Encorafenib
Treatment: Drugs - Cetuximab

Experimental: LY3214996 Dose Escalation - LY3214996 given orally once a day (or twice a day) for 21 days.

Experimental: LY3214996 + Midazolam - (Preliminary Drug-Drug Interactions \[DDI\])

LY3214996 given orally (once a day) and midazolam given orally on cycle 1 day 1 and cycle 1 day 16 (21 day cycles except cycle 1 only = 22 days).

Experimental: LY3214996 Dose Expansion - LY3214996 given orally (once a day) during each 21 day cycle.

Experimental: LY3214996 + Abemaciclib - Dose Escalation and Expansion- LY3214996 given orally (dose timing will be determined) and abemaciclib given orally (single dose given during lead in period) twice a day every 12 hours during 21 day cycle.

Experimental: LY3214996 + Nab-Paclitaxel + Gemcitabine - Dose Escalation and Expansion- LY3214996 given orally (dose timing will be determined) and nab-paclitaxel given intravenously (IV) on day 1, 8, and 15 and gemcitabine IV on day 1, 8, and 15 during each 28 day cycle.

Experimental: LY3214996 + Encorafenib + Cetuximab - Dose Escalation and Expansion- LY3214996 given orally, encorafenib given orally and cetuximab given IV.

Experimental: Japan Part 1 - LY3214996 given orally.

Experimental: Japan Part 2 - LY3214996 given orally and abemaciclib given orally.


Treatment: Drugs: LY3214996
Administered orally

Treatment: Drugs: Midazolam
Administered orally

Treatment: Drugs: Abemaciclib
Administered orally

Treatment: Drugs: Nab-paclitaxel
Administered IV

Treatment: Drugs: Gemcitabine
Administered IV

Treatment: Drugs: Encorafenib
Administered orally

Treatment: Drugs: Cetuximab
Administered IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with LY3214996 Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 (21 Days)
Secondary outcome [1] 0 0
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) of LY3214996 Administered as Monotherapy and when Administered in Combination with Nab-Paclitaxel Plus Gemcitabine, Abemaciclib and Encorafenib Plus Cetuximab
Timepoint [1] 0 0
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 28 Day Cycles)
Secondary outcome [2] 0 0
PK: AUC of Gemcitabine when Administered with LY3214996
Timepoint [2] 0 0
Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
Secondary outcome [3] 0 0
PK: AUC of Nab-Paclitaxel when Administered with LY3214996
Timepoint [3] 0 0
Cycle 1 Day 1 through Cycle 1 Day 15 (28 Day Cycles)
Secondary outcome [4] 0 0
PK: AUC of Abemaciclib and its Metabolites when Administered with LY3214996
Timepoint [4] 0 0
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Secondary outcome [5] 0 0
PK: AUC of Encorafenib when Administered with LY3214996
Timepoint [5] 0 0
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Secondary outcome [6] 0 0
PK: AUC of Cetuximab when Administered with LY3214996
Timepoint [6] 0 0
Cycle 1 Day 1 through Cycle 2 Day 1 (up to 22 Day Cycles)
Secondary outcome [7] 0 0
PK: AUC of Midazolam and its 1'-Hydroxymidazolam Metabolite when Administered Alone and in Combination with LY3214996
Timepoint [7] 0 0
Cycle 1 Day 1 through Cycle 1 Day 16 (21 Day Cycles)
Secondary outcome [8] 0 0
Objective Response Rate (ORR): Percentage of Participants With a Complete (CR) or Partial Response (PR)
Timepoint [8] 0 0
Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 6 Months)
Secondary outcome [9] 0 0
Duration of Response (DoR)
Timepoint [9] 0 0
Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 12 Months)
Secondary outcome [10] 0 0
Time to First Response (TTR)
Timepoint [10] 0 0
Baseline to Date of CR or PR (Estimated up to 6 Months)
Secondary outcome [11] 0 0
Progression Free Survival (PFS)
Timepoint [11] 0 0
Baseline to Progressive Disease or Death of Any Cause (Estimated up to 12 Months)
Secondary outcome [12] 0 0
Disease Control Rate (DCR): Percentage of Participants who Exhibit Stable Disease (SD), CR or PR
Timepoint [12] 0 0
Baseline through Measured Progressive Disease (Estimated up to 6 Months)
Secondary outcome [13] 0 0
Overall Survival (OS) (Dose Expansion Arms Only)
Timepoint [13] 0 0
Baseline to Date of Death from Any Cause (Estimated up to 2 Years)

Eligibility
Key inclusion criteria
* Have advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy.

* Part B (No Longer Enrolling Participants): Have advanced or metastatic cancer with an activating mitogen-activated protein kinase pathway alteration, BRAF mutant metastatic melanoma refractory to or relapsed after treatment with RAF and/or MEK inhibitors, metastatic melanoma with a NRAS mutation, or BRAF mutant NSCLC.
* Part C: Advanced, unresectable cancer (dose escalation) and advanced, unresectable, or metastatic non-small cell lung cancer with a BRAF or RAS mutation, or NRAS mutant melanoma (dose expansion).
* Part D (No Longer Enrolling Participants): Have metastatic pancreatic ductal adenocarcinoma (dose escalation and dose expansion).
* Part E: Metastatic BRAF V600E colorectal cancer.
* Have discontinued previous treatments for cancer and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade =1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.
* Have adequate organ function.
* Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have serious preexisting medical conditions.
* Have a known human immunodeficiency virus (HIV) infection or known activated/reactivated hepatitis A, B, or C.
* Have symptomatic central nervous system malignancy or metastasis.
* Have current hematologic malignancies, acute or chronic leukemia.
* Have a second primary malignancy that in the judgment of the investigator or Lilly may affect the interpretation of results.
* Have prior malignancies. Participants with carcinoma in situ of any origin and participants with prior malignancies who are in remission and whose likelihood of recurrence is very low, as judged by the Lilly clinical research physician, are eligible for this study.
* Have a mean QT interval corrected for heart rate (QTc) of =470 milliseconds on screening electrocardiogram (ECG) as calculated using the Bazett's formula at several consecutive days of assessment.
* Have participated, within the last 28 days in a clinical trial involving an investigational product or are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
* Have previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.
* If female, is pregnant, breastfeeding, or planning to become pregnant.
* Have history or findings of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study.
* Currently using concomitant medications that are strong inhibitors or inducers of CYP3A4.
* Part C: have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study, including interstitial lung disease (ILD) or severe dyspnea at rest or requiring oxygen therapy.
* Part C4 NRAS Melanoma: have previously completed or withdrawn from a study investigating a MEK inhibitor.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/09/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/10/2022
Sample size
Target
Accrual to date
Final
210
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New Hampshire
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
France
State/province [8] 0 0
Villejuif Cedex
Country [9] 0 0
Japan
State/province [9] 0 0
Shizuoka
Country [10] 0 0
Japan
State/province [10] 0 0
Tokyo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02857270