Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma

NCT00826241 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 999916005NCI-2012-0213116-C-N005
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 6

Brief Summary

The goal of this clinical research study is to learn if lapatinib when given in combination with temozolomide can help to control ependymoma that has come back after treatment. The safety of this combination will also be studied.

Conditions

Brain Tumors; Spinal Cord Tumors

Keywords

Brain Tumor; Central Nervous System; CNS; Spinal Cord Tumor; Anaplastic Ependymoma; Supratentorial Ependymoma; Infratentorial Ependymoma; Spinal Cord Ependymoma; Lapatinib; GW572016; Temozolomide; Temodar

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

  Assessed every two months till disease progression, up to 4 years

Secondary Outcomes (2)

• Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria

  4 weeks

• Number of Participants With Serious and Non-Serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 111 months and 26 days

Study Arms (1)

Temozolomide + Lapatinib

EXPERIMENTAL

Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth.

Drug: Temozolomide; Drug: Lapatinib

Interventions

Temozolomide DRUG

Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle.

Also known as: Temodar

Temozolomide + Lapatinib

Lapatinib DRUG

Starting dose 1250 mg daily by mouth.

Also known as: GW572016

Temozolomide + Lapatinib

Eligibility Criteria

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

You may qualify if:

• Histologically proven ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth. The patients histologic diagnosis must be confirmed on Central Pathology Review prior to registration Step 2.
• History and physical examination, including neurologic examination, within 2 weeks prior to registration.
• Patients must be able to undergo brain or spine magnetic resonance imaging (MRI) scans with intravenous gadolinium, based on tumor location(s) within 14 days prior to registration.
• Patients must be on a steroid dose that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required.
• Karnofsky performance status \>/= 70
• Age \>/= 18
• Complete blood count (CBC)/differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows: 1) Absolute neutrophil count (ANC) \>/= 1,500/mm\^3. 2) Platelets \>/= 100,000 cells/mm\^3. 3) Hemoglobin \>/= 10.0 gm/dL (Note: The use of transfusion or other intervention to achieve Hgb \>/= 10.0 is acceptable). 4) White blood cell count (WBC) \>/= 3,000/mcL.
• Adequate liver function within 14 days prior to registration, defined as follows: serum glutamic pyruvic transaminase (SGPT) \[alanine aminotransferase (ALT)\] \< 2.5 times the upper limit of normal, Bilirubin \</= 1.6 mg/dL
• Adequate renal function within 14 days prior to registration, defined as follows: Creatinine \< 1.7 mg/dL
• Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of: 1) 28 days from the administration of any investigational agent. 2) 28 days from administration of prior cytotoxic therapy with the following exceptions: (a) 14 days from administration of vincristine. (b) 42 days from administration of nitrosoureas. (c) 21 days from administration of procarbazine.
• ( 11. continued) 3) 7 days from administration of non-cytotoxic agents \[e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count)\]. 4) 28 days from prior radiation therapy.
• Patients must have recovered from the effects of surgery and a minimum of 14 days must have elapsed from the day of surgery to the day of registration. For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration.
• Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be done no later than 96 hours in the immediate postoperative period or at least 4 weeks postoperatively, within 14 days prior to registration. If the " within 96-hour of surgery " scan is more than 14 days before registration, the scan needs to be repeated.
• Patients must sign study-specific informed consent and authorization for the release of their protected health information prior to registration. Patients must be registered in the MD Anderson Cancer Center Office of Multicenter Clinical Research (MDACC OMCR) database prior to treatment with study drug.
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration.

You may not qualify if:

• Prior invasive malignancy that is not the ependymoma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years
• Transmural myocardial infarction or unstable angina within 3 months prior to study registration
• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of \>/= 2 mm using the analysis of an electrocardiography (EKG) performed within 14 days prior to registration
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
• History of stroke or transient ischemic attack within 3 months prior to registration.
• Inadequately controlled hypertension (systolic blood pressure \> 140 mm Hg and/or diastolic blood pressure \> 90 mm Hg despite antihypertensive medication)
• History of cerebral vascular accident (CVA) within 3 months prior to registration
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with acquired immunodeficiency syndrome (AIDS) from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• Pregnant or nursing women because of concern of fetal/infant exposure to these agents
• Any condition that impairs ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease).
• Patients cannot be receiving enzyme-inducing anti-epileptic Drugs (EIAEDs) nor any other Image result for CYP3A4 Cytochrome P450 3A4 (CYP3A4) inducers such as rifampin or St. John's wort beginning at least 14 days prior to registration Step 2.
• Patients cannot be receiving CYP3A4 inhibitors beginning at least 7 days prior to registration Step 2.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• CERN Foundation - Collaborative Ependymoma Research Network: collaborator

Study Sites (6)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Spinal Cord Neoplasms; Ependymoma

Interventions

Temozolomide; Lapatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Mark Gilbert
• Organization: National Cancer Institute

gilbertmr@nih.gov

240-760-6023

Study Officials

• Marta Penas-Prado, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 20, 2009
• First Posted: January 22, 2009
• Study Start: January 1, 2009
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: March 22, 2019
• Results First Posted: March 22, 2019

Record last verified: 2019-03

Locations

US (6)