Notch Inhibitor in Advanced Cancer

NCT01158404 | Completed Phase 1 Results

• 2 other identifiers: 13284I3F-MC-JSRB
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Advanced Cancer

Keywords

Metastatic Cancer; Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to study completion up to 18.7 weeks

Secondary Outcomes (4)

• Recommended Dose Range for Phase 2 Studies

  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)

  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)]

  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

  Day1: Pre-dose, 0.5 hours (hr), 1 hr, 3-4 hr, 6-8 hr and 24-30 hours post-dose

Study Arms (1)

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.

Drug: LY900009 - Dose Escalation Phase (Part A); Drug: LY900009 - Dose Confirmation Phase (Part B)

Interventions

LY900009 - Dose Escalation Phase (Part A) DRUG

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.

Also known as: Notch Inhibitor

LY900009

LY900009 - Dose Confirmation Phase (Part B) DRUG

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.

Also known as: Notch Inhibitor

LY900009

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

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, United States

Location

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, United States

Location

Related Publications (1)

• 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.

  PMID: 26798966 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2010
• First Posted: July 8, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: August 9, 2019
• Results First Posted: August 9, 2019

Record last verified: 2019-06

Locations

US (2)