Malignant Solid TumorPhase 1NCT01648764
A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread
A Phase 1 study testing LY2334737 in people with Malignant Solid Tumor and Solid Tumor, run by Eli Lilly and Company at 4 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate two different dosing regimens of LY2334737 in participants with cancer that is advanced and/or has spread to other parts of the body. Information about side effects will be collected. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Solid Tumor, Solid Tumor, Metastatic Tumor
- What is being tested?
- LY2334737
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Sep 2008to Nov 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of advanced and/or metastatic cancer (including lymphoma) for which no treatment of higher priority exists
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Estimated life expectancy of more than 12 weeks
- Have discontinued all previous therapies for cancer for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) and recovered from acute effects of therapy
- Have discontinued radiotherapy more than one week before enrolling in the study and have recovered from the acute effects of therapy
- Have adequate organ function
Show all 11Show fewer
- Follow your doctor's directions and live close enough to the study site so you can continue to go to the clinic for follow-up
- Are willing and able to swallow capsules and follow study procedures
- Have given written informed consent prior to any study-specific procedures
- Males and females with reproductive potential should use medically approved contraceptive precautions during the study and for 6 months following the last dose of study drug
- Females with child-bearing potential must have had a negative urine or serum pregnancy test 7 days prior to the first dose of study drug
Who cannot join
- Have gastrointestinal diseases or prior surgery that may interfere with the absorption of medication taken by mouth
- Females who are pregnant or lactating
- Symptomatic central nervous system malignancy or metastasis
- Known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
- Liver cirrhosis or chronic hepatitis
- Acute or chronic leukemia
- Are currently receiving treatment with valproic acid (VPA) and its derivatives, or if you have a history of intolerance to VPA
- Known hypersensitivity to gemcitabine
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Germany2 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Berlin, 13353
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Nuremberg, 90419
United States1 site
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Philadelphia, Pennsylvania, 19111
France1 site
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Clichy, 92118
About this study
Official title: Phase 1 Dose Escalation Study of LY2334737 Using 2 Dosing Regimens in Patients With Advanced and/or Metastatic Solid Tumors
The purpose of this study is to evaluate two different dosing regimens of LY2334737 in participants with cancer that is advanced and/or has spread to other parts of the body. Information about side effects will be collected.
Read the detailed description
This study will consist of a Dose Escalation Phase (Arms A and B) followed by a Dose Confirmation Phase.
- Conditions
- Malignant Solid Tumor, Solid Tumor, Metastatic Tumor
- Being tested
- LY2334737
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY2334737Drug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| LY2334737 - Arm A | Experimental | LY2334737 administered orally at escalating doses [40 milligrams (mg) - 200 mg] every other day for 21 days followed by 7 days without study drug (28 day treatment cycle). Participants may receive additional treatment cycles until discontinuation criterion is met. Receives: Drug: LY2334737 |
| LY2334737 - Arm B | Experimental | LY2334737 administered orally at escalating doses (40 mg - 200 mg) every day for 7 days followed by 7 days without study drug then repeated (28 day treatment cycle). Participants may receive additional treatment cycles until discontinuation criterion is met. Receives: Drug: LY2334737 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Dose for Phase 2 Studies
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). The MTD was the highest dose level at which <2 out of 6 participants experienced a dose-limiting toxicity (DLT) in Cycle 1. DLT was an adverse event (AE) during Cycle 1 that was likely related to LY2334737 and fulfilled any of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 nonhematological (except nausea/vomiting controlled with treatment); Grade 3 neutropenia with fever or any Grade 4 neutropenia with or without fever; Grade 3 thrombocytopenia with ≥Grade 2 bleeding or Grade 4 thrombocytopenia with or without bleeding; A recovery period longer than 14 days from last dose of LY2334737 to values allowing Cycle 2 to start; Other significant drug-related toxicity deemed by investigator to be dose limiting or that caused the participant to withdraw from the study. Pharmacokinetics and pharmacodynamics (PK/PD) were also taken into consideration for Phase 2 recommended dose.
Measured: Baseline up to 28 days postdose in Cycle 1 (28-day cycle)
Secondary outcomes (9)
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for LY2334737
AUC over the dosing interval (AUC0-Ƭ) of LY2334737 for Arm A (single dose) is 0 to 48 hours postdose. AUC0-Ƭ of LY2334737 for Arm B (multiple doses) is 0 to 24 hours postdose and AUC time 0 to infinity (AUC0-∞) for LY2334737.
Measured: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for 2'2'-Difluorodeoxycytidine (dFdC)
AUC over the dosing interval (AUC0-Ƭ) of dFdC (a metabolite of LY2334737) for Arm A (following a single dose of LY2334737) AUC0-Ƭ is 0-48 hours postdose, Arm B (following multiple doses of LY2334737) AUC 0-Ƭ is 0-24 hours postdose and AUC from time 0 to infinity (AUC0-∞).
Measured: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours post dose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours post dose of 28-day cycle
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for Difluorodeoxyuridine (dFdU)
Daily AUC from time 0 to 24 hours (AUC 0-24) of dFdU (a metabolite of LY2334737) for Arm A (single dose of LY2334737) and Arm B (multiple doses of LY2334737).
Measured: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Cmax for LY2334737 and its metabolites 2'2'-difluorodeoxycytidine (dFdC) and difluorodeoxyuridine (dFdU).
Measured: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Number of Participants With Best Overall Response (BOR)
Response defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. Complete Response defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Partial Response defined as ≥30% decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) defined as ≥20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions, or appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease was defined as small changes that did not meet above criteria and unknown defined as response status was not known. The BOR was the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).
Measured: Baseline to measured disease progression up to 33 weeks
Progression-Free Survival (PFS)
PFS was defined as the time from date of first dose to the first observation of disease progression or death due to any cause.
Due to the different tumor types, schedules and doses, the PFS was not analyzed.
Measured: Baseline to measured disease progression or death up to 33 weeks
Percentage of Participants With Changes in QT Interval (>30 Milliseconds) From Baseline
Fridericia-corrected QT (QTcF) interval corrected for heart rate was assessed using triplicate 12-lead electrocardiograms (ECGs). Change in QT interval from baseline was calculated using a time matched approach, that is change from baseline was calculated by subtracting the respective reading taken at the same nominal time on Day-1 from the reading taken on Days 1 and 21; change from baseline was calculated by subtracting the last non-missing ECG assessment on or prior to Day 1, 0.5 hours prior to dose from assessment on Day 2 and Day 22. The outlying QTcF intervals were defined using the criteria: change from baseline in mean QTcF interval >30 milliseconds
Measured: Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21, 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose (28-day cycles)
Percentage of Participants With Changes in R-R Interval From Baseline
Changes in R-R interval from baseline was calculated using a time matched approach, that is change from baseline was calculated by subtracting the respective reading taken at the same nominal time on Day -1 from the reading taken on Days 1 and 21; change from baseline was calculated by subtracting the last non-missing electrocardiogram (ECG) assessment on or prior to Day 1 and 0.5 hours prior to dose for Day 2 and Day 22. Percentage of participants with changes in R-R interval from baseline was calculated as the number of participants with a change not equal to 0 across all time points divided by the number of treated participants multiplied by 100.
Measured: Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21: 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose
Pharmacokinetics: Minimum Plasma Concentration (Cmin)
Cmin for LY2334737 and its metabolite 2'2'-difluorodeoxycytidine (dFdC).
Measured: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7, 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2012 (estimated)
- Study startSep 2008
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Solid TumorStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01648764
- Sponsor's protocol ID
- 11967
- Other IDs
- 2008-000807-28, I1C-MC-JLBE, 2008
- Status last verified
- Mar 2019
- First submitted
- 20 Jul 2012
- Last updated
- 17 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Dose Escalation Study of LY2334737 Using 2 Dosing Regimens in Patients With Advanced and/or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT01648764
- Acronym / sponsor ID
- 11967
- Conditions
- Malignant Solid Tumor, Solid Tumor, Metastatic Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Sep 2008
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 24 Jul 2012 (estimated)
- Results
- Posted 17 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate two different dosing regimens of LY2334737 in participants with cancer that is advanced and/or has spread to other parts of the body. Information about side effects will be collected.
Detailed description
This study will consist of a Dose Escalation Phase (Arms A and B) followed by a Dose Confirmation Phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LY2334737 - Arm A | Experimental | Drug: LY2334737LY2334737 administered orally at escalating doses [40 milligrams (mg) - 200 mg] every other day for 21 days followed by 7 days without study drug (28 day treatment cycle). Participants may receive additional treatment cycles until discontinuation criterion is met. |
| LY2334737 - Arm B | Experimental | Drug: LY2334737LY2334737 administered orally at escalating doses (40 mg - 200 mg) every day for 7 days followed by 7 days without study drug then repeated (28 day treatment cycle). Participants may receive additional treatment cycles until discontinuation criterion is met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosis of advanced and/or metastatic cancer (including lymphoma) for which no treatment of higher priority exists
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Estimated life expectancy of more than 12 weeks
- Have discontinued all previous therapies for cancer for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) and recovered from acute effects of therapy
- Have discontinued radiotherapy more than one week before enrolling in the study and have recovered from the acute effects of therapy
Key exclusion criteria (8 listed)
- Have gastrointestinal diseases or prior surgery that may interfere with the absorption of medication taken by mouth
- Females who are pregnant or lactating
- Symptomatic central nervous system malignancy or metastasis
- Known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
- Liver cirrhosis or chronic hepatitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY2334737Administered orally | Drug | LY2334737 - Arm A, LY2334737 - Arm B |
Primary outcome
Recommended Dose for Phase 2 Studies
Time frame: Baseline up to 28 days postdose in Cycle 1 (28-day cycle)
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). The MTD was the highest dose level at which <2 out of 6 participants experienced a dose-limiting toxicity (DLT) in Cycle 1. DLT was an adverse event (AE) during Cycle 1 that was likely related to LY2334737 and fulfilled any of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 nonhematological (except nausea/vomiting controlled with treatment); Grade 3 neutropenia with fever or any Grade 4 neutropenia with or without fever; Grade 3 thrombocytopenia with ≥Grade 2 bleeding or Grade 4 thrombocytopenia with or without bleeding; A recovery period longer than 14 days from last dose of LY2334737 to values allowing Cycle 2 to start; Other significant drug-related toxicity deemed by investigator to be dose limiting or that caused the participant to withdraw from the study. Pharmacokinetics and pharmacodynamics (PK/PD) were also taken into consideration for Phase 2 recommended dose.
9 secondary outcomes
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for LY2334737
Time frame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for 2'2'-Difluorodeoxycytidine (dFdC)
Time frame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours post dose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours post dose of 28-day cycle
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for Difluorodeoxyuridine (dFdU)
Time frame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Time frame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Number of Participants With Best Overall Response (BOR)
Time frame: Baseline to measured disease progression up to 33 weeks
Progression-Free Survival (PFS)
Time frame: Baseline to measured disease progression or death up to 33 weeks
Percentage of Participants With Changes in QT Interval (>30 Milliseconds) From Baseline
Time frame: Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21, 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose (28-day cycles)
Percentage of Participants With Changes in R-R Interval From Baseline
Time frame: Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21: 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose
Pharmacokinetics: Minimum Plasma Concentration (Cmin)
Time frame: Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7, 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY2334737 in people with Malignant Solid Tumor and Solid Tumor, run by Eli Lilly and Company at 4 sites in 3 countries.
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 11 inclusion and 8 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: finished, as of the sponsor's last update on 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, United States, France. 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?
Yes. Results are posted in the registry (first posted 17 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Recommended Dose for Phase 2 Studies (time frame: Baseline up to 28 days postdose in Cycle 1 (28-day cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jun 2019.