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

NCT01115803 | Terminated Phase 1 Results

• 2 other identifiers: 12531I3G-MC-JGCB
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (1)

• Recommended Dose for Phase 2 Studies

  The recommended dose for the Phase 2 (Dose Confirmation Phase) study was determined by safety assessment. Doses were escalated following the assessment for toxicity based on Common Terminology Criteria for Adverse Events (CTCAE v4.0). Any adverse events (AE) that were possibly related to LY2584702 were considered toxicities. The Phase 2 dose of LY2584702 was not determined due to unacceptable toxicities of LY2584702 in combination with erlotinib or everolimus in Phase 1 of the study.

  Baseline up to 6 cycles of 28 days

Secondary Outcomes (6)

• Clinically Significant Effects (Number of Participants With Adverse Events)

  Baseline up to 7 months

• Progression-Free Survival (PFS)

  Baseline to disease progression or death or up to 166 days postbaseline

• Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)]

  Baseline to disease progression or death or up to 6 cycles of 28 days

• Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702

  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

• Pharmacokinetics, Area Under the Concentration Time Curve (AUC)

  Cycle 1 Days 1 (C1 D1) and Cycle 1 Day 8 (C1 D8) of 28-day cycle

Other Outcomes (1)

• Number of Participants Who Died Due to Progressive Disease Within 30 Days of Study Drug Discontinuation

  Within 30 days of study drug discontinuation

Study Arms (2)

Arm A: LY2584702 + Erlotinib

EXPERIMENTAL

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.

Drug: LY2584702; Drug: Erlotinib

Arm B: LY2584702 + Everolimus

EXPERIMENTAL

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.

Drug: LY2584702; Drug: Everolimus

Interventions

LY2584702 DRUG

Supplied as 25 milligrams (mg) and 100 mg capsules, administered orally for two 28-day cycles.

Arm A: LY2584702 + Erlotinib; Arm B: LY2584702 + Everolimus

Erlotinib DRUG

Supplied as 25 mg, 100 mg, or 150 mg tablets, administered orally, daily for two 28-day cycles. Starting dose is 150mg. Doses may be decreased in 50mg increments if necessary due to toxicity.

Arm A: LY2584702 + Erlotinib

Everolimus DRUG

Supplied as 5 mg or 10 mg tablets, administered orally, daily for two 28-day cycles.

Arm B: LY2584702 + Everolimus

Eligibility Criteria

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

You may qualify if:

• 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:
• Arm A: advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
• 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.
• Dose Escalation portion (Part 1): participants may have measurable or nonmeasurable disease.
• Dose Confirmation portion (Part 2): participants must have measurable disease.
• Have adequate organ function including:
• 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).
• 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.

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 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

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.

Chicago, Illinois, 60637, 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.

Bordeaux, 33076, France

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.

Villejuif, 94805, France

Location

Related Publications (1)

• 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.

  PMID: 24456794 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Neuroendocrine Tumors

Interventions

LY2584702; Erlotinib Hydrochloride; Everolimus

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Study terminated early. Dose confirmation, Part B, was not initiated.

Results Point of Contact

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

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM - 5PM 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2010
• First Posted: May 4, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: February 5, 2019
• Results First Posted: January 18, 2019

Record last verified: 2019-01

Locations

FR (2); US (1)