Clinical trial NCT01115803: A Study of LY2584702 With Erlotinib or Everolimus in Participants With Solid Tumors
Official title: A Phase 1b Trial of LY2584702 in Combination With Erlotinib or Everolimus in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastases, Neoplasm
Carcinoma, Non-small Cell Lung
Renal Cell Carcinoma
Neuroendocrine Tumors
Keywords: Advanced Cancer
Metastatic Cancer
Non-Small Cell Lung Cancer
Renal Cell Carcinoma
Neuroendocrine Tumors
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-05-04
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recommended Dose for Phase 2 Studies
timeFrame: Baseline up to 6 cycles of 28 days
Secondary outcomes:
measure: Clinically Significant Effects (Number of Participants With Adverse Events)
timeFrame: Baseline up to 7 months
measure: Progression-Free Survival (PFS)
timeFrame: Baseline to disease progression or death or up to 166 days postbaseline
measure: Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)]
timeFrame: Baseline to disease progression or death or up to 6 cycles of 28 days
measure: Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702
timeFrame: Cycle 1 Day 1 (C1 D1): predose, 0.5, 1, 2, 3, 5, 8 hours postdose and Cycle 1 Day 8 (C1 D8): predose, 0.5, 1, 2, 3, 5, and 8 hours postdose of 28-day cycle
measure: Pharmacokinetics, Area Under the Concentration Time Curve (AUC)
timeFrame: Cycle 1 Days 1 (C1 D1) and Cycle 1 Day 8 (C1 D8) of 28-day cycle
measure: Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)]
timeFrame: Baseline up to 112 Days
Other outcomes:
measure: Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation
timeFrame: Within 30 days of study drug discontinuation
Locations:
city: Chicago
country: United States
facility: 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.
state: Illinois
city: Bordeaux
country: France
facility: 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.
city: Villejuif
country: France
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Hollebecque A, Houede N, Cohen EE, Massard C, Italiano A, Westwood P, Bumgardner W, Miller J, Brail LH, Benhadji KA, Soria JC. A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours. Eur J Cancer. 2014 Mar;50(5):876-84. doi: 10.1016/j.ejca.2013.12.006. Epub 2014 Jan 20.