Advanced CancerPhase 1NCT01158404

Notch Inhibitor in Advanced Cancer

A Phase 1 study testing LY900009 - Dose Escalation Phase (Part A) and LY900009 - Dose Confirmation Phase (Part B) in people with Advanced Cancer, run by Eli Lilly and Company at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objective of this phase 1 study is to evaluate the safety and tolerability of Notch Inhibitor in participants with advanced cancer. This study includes dose escalation and dose confirmation components. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Cancer
What is being tested?: LY900009 - Dose Escalation Phase (Part A) and LY900009 - Dose Confirmation Phase (Part B)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 2 sitesUnited States
Study dates: Jul 2010to Aug 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

The participants must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease.
The participants must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic.
Have adequate organ function including:
Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/liter (L), platelets ≥100 x 10⁹/L, and hemoglobin ≥8 grams/deciliter (g/dL).
Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN) and alanine aminotransferase (ALT) ≤3.0 times ULN.
Renal: Serum creatinine ≤1.5 times ULN.

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Have a performance status less than or equal to 1 for Dose Escalation and less than or equal to 2 for Dose Confirmation on the Eastern Cooperative Oncology Group (ECOG) scale.
Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia.
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug.
Females with childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study drug.

Who cannot join

Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, inflammatory bowel disease or history of major surgical resection involving the stomach or small bowel).
Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).
Females who are pregnant or lactating.
Have Central Nervous System (CNS) malignancy or metastasis.
Have an acute leukemia.
Have active bacterial, fungal and/or known viral infection.

Trial locations and contacts

2 sites in 1 country.

United States2 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.
Nashville, Tennessee, 37203
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.
Oklahoma City, Oklahoma, 73104

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About this study

Official title: Phase 1 Study of a Notch Inhibitor in Patients With Advanced Cancer

Conditions: Advanced Cancer
Being tested: LY900009 - Dose Escalation Phase (Part A), LY900009 - Dose Confirmation Phase (Part B)
Keywords: Metastatic Cancer, Solid Tumors
Medical subject headings: Neoplasm Metastasis

What participants receive

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

LY900009 - Dose Escalation Phase (Part A)Drug
Also called Notch Inhibitor
2 milligrams (mg), 4 mg, 8 mg, 15 mg, 30 mg, 45 mg and 60mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle.
Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.
LY900009 - Dose Confirmation Phase (Part B)Drug
Also called Notch Inhibitor
30 mg LY900009 orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle.
Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.

Study groups in NCT01158404
Study group	Role	What they receive
LY900009	Experimental	Dose escalation phase: 2 milligrams (mg), 4 mg, 8 mg, 15 mg, 30 mg, 45 mg and 60mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle. Dose confirmation phase: 30 mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle. Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met. Receives: Drug: LY900009 - Dose Escalation Phase (Part A); Drug: LY900009 - Dose Confirmation Phase (Part B)

What is being measured

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

Number of Participants With Clinically Significant Effects
Clinically significant effects are study drug related serious adverse events (SAEs) and study drug related treatment emergent adverse events (TEAEs). A summary of all SAEs and all other non-SAEs regardless of causality is located in the Reported Adverse Events module.
Measured: Baseline to study completion up to 18.7 weeks

Secondary outcomes (4)

Recommended Dose Range for Phase 2 Studies
Recommended Phase 2 dose was determined by the maximum tolerated dose (MTD). MTD is the highest dose with <33% of participants having a dose-limiting toxicity (DLT) during Cycle 1. DLT is an adverse event (AE) occurring for a participant enrolled in Part A that is likely related to the study drug and fulfills any 1 of the following: Common Terminology Criteria for AE (CTCAE, Version 4.02) Grade 3 or 4 nonhematologic toxicity except for Grade 3 nausea, vomiting or electrolyte disturbance; Grade 3 nausea, vomiting or electrolyte disturbance that persists more than 2 days despite maximal supportive intervention; Grade 4 hematological toxicity that persists more than 5 days; Grade 3 or 4 thrombocytopenia with bleeding; Grade 3 or 4 neutropenia with fever. A DLT can be declared if a participant experiences increasing toxicity during treatment.
Measured: Predose up to 28 days in Cycle 1
Percentage of Participants With a Best Overall Response of Stable Disease or Better (Document the Antitumor Activity)
Best overall response of stable disease or better is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.1). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Percentage of Participants with a best overall response of SD or better is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated then multiplied by 100.
Measured: Baseline to measured progressive disease up to 15.1 weeks
Pharmacokinetics: Area Under the Concentration-time Curve of LY900009 From Time Zero to Infinity [AUC(0-infinity)]
The geometric mean AUC(0-infinity) for each dose group is reported following a single dose of LY900009.
Measured: Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose
Pharmacokinetics: Maximum Concentration (Cmax) of LY900009
The geometric mean Cmax for each dose group is reported following a single dose of LY900009.
Measured: Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose

Timeline

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

Jul 2010Aug 2012

First posted8 Jul 2010 (estimated)
Study startJul 2010
Primary completionAug 2012
Study completionAug 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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced CancerStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01158404
Sponsor's protocol ID: 13284
Other IDs: I3F-MC-JSRB
Status last verified: Jun 2019
First submitted: 6 Jul 2010
Last updated: 9 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Pant S, Jones SF, Kurkjian CD, Infante JR, Moore KN, Burris HA, McMeekin DS, Benhadji KA, Patel BKR, Frenzel MJ, Kursar JD, Zamek-Gliszczynski MJ, Yuen ESM, Chan EM, Bendell JC. A first-in-human phase I study of the oral Notch inhibitor, LY900009, in patients with advanced cancer. Eur J Cancer. 2016 Mar;56:1-9. doi: 10.1016/j.ejca.2015.11.021. Epub 2016 Jan 19.
PubMed 26798966

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1 Study of a Notch Inhibitor in Patients With Advanced Cancer
ClinicalTrials.gov ID: NCT01158404
Acronym / sponsor ID: 13284
Conditions: Advanced Cancer
Keywords: Metastatic Cancer, Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Jul 2010
Primary completion: Aug 2012 (actual)
Study completion: Aug 2012 (actual)
First posted: 8 Jul 2010 (estimated)
Results: Posted 9 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
LY900009	Experimental	Drug: LY900009 - Dose Escalation Phase (Part A), Drug: LY900009 - Dose Confirmation Phase (Part B)Dose escalation phase: 2 milligrams (mg), 4 mg, 8 mg, 15 mg, 30 mg, 45 mg and 60mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle. Dose confirmation phase: 30 mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle. Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

The participants must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease.
The participants must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic.
Have adequate organ function including:
Have a performance status less than or equal to 1 for Dose Escalation and less than or equal to 2 for Dose Confirmation on the Eastern Cooperative Oncology Group (ECOG) scale.
Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia.

Key exclusion criteria (7 listed)

Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, inflammatory bowel disease or history of major surgical resection involving the stomach or small bowel).
Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).
Females who are pregnant or lactating.
Have Central Nervous System (CNS) malignancy or metastasis.

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
LY900009 - Dose Escalation Phase (Part A)Also: Notch Inhibitor2 milligrams (mg), 4 mg, 8 mg, 15 mg, 30 mg, 45 mg and 60mg LY900009 administered orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle. Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.	Drug	LY900009
LY900009 - Dose Confirmation Phase (Part B)Also: Notch Inhibitor30 mg LY900009 orally 3 times per week (Monday, Wednesday, Friday) for 4 weeks of a 28-day cycle. Participants experiencing clinical benefit may continue treatment unless discontinuation criteria are met.	Drug	LY900009

Primary outcome

Number of Participants With Clinically Significant Effects
Time frame: Baseline to study completion up to 18.7 weeks
Clinically significant effects are study drug related serious adverse events (SAEs) and study drug related treatment emergent adverse events (TEAEs). A summary of all SAEs and all other non-SAEs regardless of causality is located in the Reported Adverse Events module.

4 secondary outcomes

Recommended Dose Range for Phase 2 Studies
Time frame: Predose up to 28 days in Cycle 1
Percentage of Participants With a Best Overall Response of Stable Disease or Better (Document the Antitumor Activity)
Time frame: Baseline to measured progressive disease up to 15.1 weeks
Pharmacokinetics: Area Under the Concentration-time Curve of LY900009 From Time Zero to Infinity [AUC(0-infinity)]
Time frame: Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose
Pharmacokinetics: Maximum Concentration (Cmax) of LY900009
Time frame: Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose

Results and safety

Results posted to the registry on 9 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
2 mg LY900009 - Dose Escalation Phase (Part A)	3	3
4 mg LY900009 - Dose Escalation Phase (Part A)	4	3
8 mg LY900009 - Dose Escalation Phase (Part A)	3	3
15 mg LY900009 - Dose Escalation Phase (Part A)	3	3
30 mg LY900009 - Dose Escalation Phase (Part A)	6	3
45 mg LY900009 - Dose Escalation Phase (Part A)	5	4
60 mg LY900009 - Dose Escalation Phase (Part A)	3	2
30 mg LY900009 - Dose Confirmation Phase (Part B)	8	6

Primary outcome: Number of Participants With Clinically Significant Effects

Time frame: Baseline to study completion up to 18.7 weeks. Count of participants. Unit: Participants

Measure	2 mg LY900009 - Dose Escalation Phase (Part A) n = 3	4 mg LY900009 - Dose Escalation Phase (Part A) n = 4	8 mg LY900009 - Dose Escalation Phase (Part A) n = 3	15 mg LY900009 - Dose Escalation Phase (Part A) n = 3	30 mg LY900009 - Dose Escalation Phase (Part A) n = 6	45 mg LY900009 - Dose Escalation Phase (Part A) n = 5	60 mg LY900009 - Part A: Dose Escalation n = 3	30 mg LY900009 - Dose Confirmation Phase (Part B) n = 8
SAEs	0	1	0	0	0	0	1	2
TEAEs	2	1	3	3	5	5	2	6

Population analysed: All enrolled participants who received at least one dose of study drug.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up To 18.7 Weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
2 mg LY900009 - Dose Escalation Phase (Part A)	0 of 3 (0%)	3 of 3 (100%)	Not reported
4 mg LY900009 - Dose Escalation Phase (Part A)	1 of 4 (25%)	3 of 4 (75%)	Not reported
8 mg LY900009 - Dose Escalation Phase (Part A)	0 of 3 (0%)	3 of 3 (100%)	Not reported
15 mg LY900009 - Dose Escalation Phase (Part A)	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
30 mg LY900009 - Dose Escalation/Confirmation Phase (Part A,B)	7 of 14 (50%)	14 of 14 (100%)	Not reported
45 mg LY900009 - Dose Escalation Phase (Part A)	3 of 5 (60%)	5 of 5 (100%)	Not reported
60 mg LY900009 - Dose Escalation Phase (Part A)	2 of 3 (66.7%)	3 of 3 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26798966Pant S, Jones SF, Kurkjian CD, Infante JR, Moore KN, Burris HA, McMeekin DS, Benhadji KA, Patel BKR, Frenzel MJ, Kursar JD, Zamek-Gliszczynski MJ, Yuen ESM, Chan EM, Bendell JC. A first-in-human phase I study of the oral Notch inhibitor, LY900009, in patients with advanced cancer. Eur J Cancer. 2016 Mar;56:1-9. doi: 10.1016/j.ejca.2015.11.021. Epub 2016 Jan 19.

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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

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 7 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 9 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

Yes. Results are posted in the registry (first posted 9 Aug 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?

Number of Participants With Clinically Significant Effects (time frame: Baseline to study completion up to 18.7 weeks). 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 NCT01158404, 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 9 Aug 2019.