Notch Inhibitor in Advanced Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Advanced Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01158404

13284

I3F-MC-JSRB (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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 design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

LY900009

Experimental group

Description:

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.

Treatment:

Drug: LY900009 - Dose Escalation Phase (Part A)

Drug: LY900009 - Dose Confirmation Phase (Part B)