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

This study has been terminated.
(Primary objective has been met; safety and pharmacokinetics have been characterized.)
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01115803
First received: April 22, 2010
Last updated: January 6, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Metastases, Neoplasm
Carcinoma, Non-small Cell Lung
Renal Cell Carcinoma
Neuroendocrine Tumors
Drug: LY2584702
Drug: Erlotinib
Drug: Everolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Trial of LY2584702 in Combination With Erlotinib or Everolimus in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended dose for Phase 2 studies [ Time Frame: Baseline to study completion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinically significant effects [ Time Frame: Baseline to study completion ] [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) [ Time Frame: Baseline to disease progression or death. Tumor assessments are performed every 2 cycles until disease progression and during post-study follow-up period. ] [ Designated as safety issue: No ]
  • Response rate (RR), the proportion of patients achieving a response of confirmed partial or complete response (CR+PR). [ Time Frame: Baseline to disease progression or death. Tumor assessments are performed every 2 cycles until disease progression and during post-study follow-up period. ] [ Designated as safety issue: No ]
  • Pharmacokinetics, maximum concentration (Cmax) [ Time Frame: Baseline, Days 1, 2, 8, 15, 22 of Cycle 1, and Day 1 of Cycle 2 ] [ Designated as safety issue: No ]
  • Pharmacokinetics, area under the curve (AUC) [ Time Frame: Baseline, Days 1, 2, 8, 15, 22 of Cycle 1, and Day 1 of Cycle 2 ] [ Designated as safety issue: No ]
  • Best overall response (CR+PR+SD) [ Time Frame: Baseline to disease progression. Tumor assessments are performed every 2 cycles until disease progression and during post-study follow-up period. ] [ Designated as safety issue: No ]

Estimated Enrollment: 85
Study Start Date: March 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: LY2584702 + Erlotinib Drug: LY2584702

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

Starting dose is 50mg. Dose will be subsequently increased to 100mg, 200mg, and 300mg.

Drug: Erlotinib

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.

Experimental: Arm B: LY2584702 + Everolimus Drug: LY2584702

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

Starting dose is 50mg. Dose will be subsequently increased to 100mg, 200mg, and 300mg.

Drug: Everolimus

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

Starting dose is 10mg. Doses may be reduced to 5mg if necessary due to toxicity.


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 patients with advanced or metastatic cancer.

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

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

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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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): patients may have measurable or nonmeasurable disease.
    2. Dose Confirmation portion (Part 2): patients must have measurable disease.
  • Have adequate organ function including:

    1. Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, and hemoglobin greater than or equal to 8 g/dL.
    2. Hepatic: bilirubin less than or equal to 1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and 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. Patients 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 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, patients with prostate cancers progressing under LHRH agonists therapy, and patients with adrenal carcinomas using mitotan, 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 CNS malignancy or metastasis. Patients 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 patients without history of CNS metastasis is not required.
  • Concomitant treatment by strong CYP3A4 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 allogenic 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01115803

Locations
United States, Illinois
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, United States, 60637
France
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, France, 33076
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, France, 94805
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01115803     History of Changes
Other Study ID Numbers: 12531, I3G-MC-JGCB
Study First Received: April 22, 2010
Last Updated: January 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced Cancer
Metastatic Cancer
Non-Small Cell Lung Cancer
Renal Cell Carcinoma
Neuroendocrine Tumors

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Neoplasm Metastasis
Neuroendocrine Tumors
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Neoplastic Processes
Pathologic Processes
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Erlotinib

ClinicalTrials.gov processed this record on April 17, 2014