A Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors

Lilly

Status and phase: Terminated; Phase 1

Conditions: Neuroendocrine Tumors; Metastases, Neoplasm; Renal Cell Carcinoma; Carcinoma, Non-small Cell Lung

Treatments: Drug: Erlotinib; Drug: Everolimus; Drug: LY2584702

Study type: Interventional

Funder types: Industry

Identifiers

NCT01115803

12531

I3G-MC-JGCB (Other Identifier)

Details and patient eligibility

About

Study I3G-MC-JGCB (JGCB) is a multicenter, nonrandomized, open-label, dose-escalation Phase 1b study of LY2584702 in combination with either erlotinib or everolimus.

Full description

Study JGCB will consist of the following parts:

Part 1 - Dose Escalation to maximum tolerated dose in each arm.

Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic cancer.

Arm B - LY2584702 + Everolimus in participants with advanced or metastatic cancer.

Part 2 - Dose Confirmation of maximum tolerated dose from each arm in Part 1.

Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic non-small cell lung cancer.

Arm B - LY2584702 + Everolimus in participants with advanced renal cell carcinoma after treatment failure with sunitinib or sorafenib, or advanced neuroendocrine tumors.

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) for which no proven effective therapy exists.

• Dose Confirmation portion (Part 2): have histological or cytological evidence of:

  1. Arm A: advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
  2. Arm B: advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib, or advanced neuroendocrine tumors.

• Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma.

  1. Dose Escalation portion (Part 1): participants may have measurable or nonmeasurable disease.
  2. Dose Confirmation portion (Part 2): participants must have measurable disease.

• Have adequate organ function including:

  1. Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10⁹/liters (L), platelets greater than or equal to 100 x 10⁹/L, and hemoglobin greater than or equal to 8 grams/deciliter (g/dL).
  2. Hepatic: bilirubin less than or equal to 1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling less than or equal to 5 times ULN are acceptable. Participants with bone metastases may enter with alkaline phosphatase values less than or equal to 5 times ULN, as long as other hepatic parameters meet inclusion criteria.
  3. Renal: Serum creatinine less than or equal to 1.5 times ULN or calculated creatinine clearance >45 milliliter/minute (ml/mn).

• Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrollment, and have recovered from the acute effects of therapy. At the discretion of the investigator, participants with prostate cancers progressing under luteinizing hormone-releasing hormone (LHRH) agonists therapy, and participants with adrenal carcinomas using mitotane, may have that treatment continued while receiving 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 opinion of the investigator, would preclude participation in this study.
• Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable and asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required.
• Concomitant treatment by strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers.
• Have an acute or chronic leukemia.
• Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogeneic stem-cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
• For Dose Confirmation portion (Part 2): have previously received erlotinib for Arm A or everolimus for Arm B.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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29 participants in 2 patient groups

Arm A: LY2584702 + Erlotinib

Experimental group

Description:

Participants received 50 mg LY2584702 once daily (QD )+ 150 mg Erlotinib QD, 50 mg LY2584702 twice daily (BID) + 150 mg Erlotinib QD, 100 mg LY2584702 BID + 150 mg Erlotinib QD and 75 mg LY2584702 BID + 150 mg Erlotinib QD.

Treatment:

Drug: LY2584702

Drug: Erlotinib

Arm B: LY2584702 + Everolimus

Experimental group

Description:

Participants received 50 mg LY2584702 QD + 10 mg Everolimus QD, 100 mg LY2584702 QD + 10 mg Everolimus QD and 50 mg LY2584702 BID + 10 mg Everolimus QD.

Treatment:

Drug: Everolimus

Drug: LY2584702