A Study of LY2940680 in Pediatric Medulloblastoma or Rhabdomyosarcoma

This study has been withdrawn prior to enrollment.
(Trial stopped early for poor accrual.)
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01697514
First received: September 28, 2012
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to find a recommended dose level of LY2940680 that can be safely given to children with medulloblastoma or rhabdomyosarcoma that has returned or doesn't respond to initial treatment. The study will also explore the changes in a cancer marker levels. Finally, the study will help document any antitumor activity.


Condition Intervention Phase
Medulloblastoma, Childhood
Rhabdomyosarcoma
Drug: LY2940680
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of LY2940680 in Pediatric Patients With Recurrent or Refractory Rhabdomyosarcoma or Medulloblastoma

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Maximum Tolerated Dose of LY2940680 [ Time Frame: Baseline to Part A Completion (estimated as 12 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of LY2940680 and LSN2941091 [ Time Frame: Predose up to 24 hours Postdose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum Concentration (Cmax) of LY2940680 and LSN2941091 [ Time Frame: Predose up to 24 hours Postdose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2940680 and LSN2941091 [ Time Frame: Predose up to 24 hours Postdose ] [ Designated as safety issue: No ]
  • Number of Participants with Tumor Response [ Time Frame: Baseline to Study Completion (estimated as 44 months) ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: July 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: LY2940680 (Dose Escalation)
LY2940680 administered orally once daily at escalating doses (92.5 milligrams per square meter [mg/m^2] up to 370 mg/m^2) for two 28 day cycles. Lower dose levels (23 mg/m^2 and 46 mg/m^2) may also be explored, if necessary. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
Drug: LY2940680
Capsule administered orally.
Drug: LY2940680
Powder administered orally (may be sprinkled on soft food).
Experimental: Part B: LY2940680 (Dose Confirmation)
LY2940680 administered orally once daily for two 28 day cycles. Dose based on Part A. Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
Drug: LY2940680
Capsule administered orally.
Drug: LY2940680
Powder administered orally (may be sprinkled on soft food).

  Eligibility

Ages Eligible for Study:   12 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Part A: Have a diagnosis of recurrent or refractory rhabdomyosarcoma or medulloblastoma and have had histologic verification of malignancy at original diagnosis or relapse.
  • For Part B: Have a diagnosis of recurrent or refractory medulloblastoma and have had histologic verification of malignancy at original diagnosis or relapse.
  • Current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
  • Karnofsky score must be at least 50% for participants >16 years of age, and Lansky score must be at least 50% for participants 16 years of age or less. Participants who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Have fully recovered from the acute toxic effects of all prior anticancer chemotherapy.

    • Participants with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment in this study (6 weeks, if previously treated with nitrosourea).
    • Hematopoietic growth factors: At least 14 days after the last dose of a longacting growth factor (eg, Neulasta®) or 7 days for short-acting growth factor.
    • Biologic (antineoplastic agent): At least 7 days after the last dose of a biologic agent.
    • Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy (eg, tumor vaccines).
    • Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
    • Radiation therapy (XRT): ≥8 weeks for local irradiation to primary tumor;≥2 weeks prior to study entry for focal irradiation for symptomatic metastatic sites; ≥3 months for craniospinal XRT, or ≥24 weeks if ≥50% radiation of pelvis; minimum of 6 weeks must have elapsed if other substantial bone marrow radiation has been received.
    • Stem cell transplant: allowed if they have recovered from all acute toxicity and adequate bone marrow reserve is demonstrated. At least 8 weeks must have elapsed since autologous stem cell transplantation or ≥3 months for allogenic transplantation. Participants must be off all immunosuppressive therapy and have no evidence of active graft-versus-host disease.
  • Have adequate organ function, including:

    • Bone marrow: Peripheral absolute neutrophil count (ANC) ≥500/cubic millimeter (mm^3) and platelet count ≥100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment).
    • Hepatic: Bilirubin (sum of conjugated + unconjugated)≤1.5 × upper limit of normal (ULN) for age. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.0 times ULN for age. Serum albumin ≥2 grams/deciliter (g/dL).
    • Renal: Creatinine clearance or radioisotope glomerular filtration rate (GFR)

      ≥70 milliliters/minute/1.73 square meters (mL/min/1.73 m^2), or a serum creatinine based on age/gender per the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC).

    • Neurologic: Participants with seizure disorders may be enrolled if receiving nonenzyme-inducing anticonvulsants and if the symptoms are well controlled. They must have a stable neurologic status for at least 1 week prior to enrollment in the study.
  • Must be able to swallow powder or a capsule.
  • Have the presence of either measurable or nonmeasurable disease.

Exclusion Criteria:

  • Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.
  • Receiving corticosteroids and have not been on a stable or decreasing dose of corticosteroid for the prior 7 days.
  • Receiving enzyme-inducing anticonvulsants.
  • Have serious preexisting medical conditions.
  • Have current hematologic malignancies or acute or chronic leukemia.
  • Have a known active fungal, bacterial, and/or known viral infection, including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
  • Have a second primary malignancy that, in the judgment of the investigator and sponsor, may affect the interpretation of results.
  • Have ≥Grade 2 QT prolongation, that is, QTc interval of >480 milliseconds (msec) on screening electrocardiography (ECG).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01697514

Locations
United States, California
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.
San Diego, California, United States, 92123
United States, Colorado
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.
Aurora, Colorado, United States, 80045
United States, Ohio
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.
Cincinnati, Ohio, United States, 45229
United States, Oregon
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.
Portland, Oregon, United States, 97239
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 9 AM - 5 PM 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: NCT01697514     History of Changes
Other Study ID Numbers: 14492, I4J-MC-HHBD
Study First Received: September 28, 2012
Last Updated: August 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
recurrent medulloblastoma

Additional relevant MeSH terms:
Medulloblastoma
Rhabdomyosarcoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma

ClinicalTrials.gov processed this record on August 26, 2014