Oral Pazopanib Plus Oral Topotecan Metronomic Antiangiogenic Therapy for Recurrent Glioblastoma Multiforme (A) Without Prior Bevacizumab Exposure and (B) After Failing Prior Bevacizumab

NCT01931098 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16003416-C-0034
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glioblastoma is the most common and most aggressive type of malignant brain tumor. The drug pazopanib is used to treat people with a type of kidney cancer. Topotecan is used to treat lung cancer. Both topotecan and pazopanib have individually been used to treat patients with glioblastoma and some anti-tumor activity has been found. Researchers want to see if these two drugs together may be able to help people with glioblastoma. Objectives: To learn if pazopanib with topotecan can help control glioblastoma. Also, to study the safety of this drug combination. Eligibility: Adults at least 18 years old whose glioblastoma has returned after treatment. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Brain computed tomography (CT) or magnetic resonance imaging (MRI) For these, participants lay in a machine that takes pictures. Chest CT scan or x-ray Heart electrocardiogram (EKG) A questionnaire about quality of life Participants will be assigned to a study group. Participants will take the study drugs for 28-day cycles for up to 1 year. They will take capsules of topotecan by mouth once every day. They will take tablets of pazopanib by mouth once every day. Participants will write in a diary the times they take the study drugs. Participants will have several study visits during each cycle. These may include Blood pressure measurement Blood and urine tests EKG Physical exam and/or neurological exam Brain MRI or CT scan to check the status of the disease A symptom questionnaire At the end of treatment, participants will have a physical exam. They may have blood drawn. Participants will have follow-up calls once every 3 months to check.

Conditions

Glioblastoma; Glioblastoma Multiforme; Gliosarcoma; Brain Neoplasms; Central Nervous System Neoplasms

Keywords

Brain Tumors

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients That Have Progressive Survival (PFS) at Six Months From Patient Registration for Bevacizumab Naive Patients and PFS at 3 Months for Patients With Prior Bevacizumab Treatment

  PFS was evaluated using the Kaplan-Meier product-limit survival curve methodology. For participants with no prior bevacizumab exposure, PFS is defined as 2 or more participants who are progression free at 6 months. For participants with prior bevacizumab exposure, PFS is defined as 1 or more participants who are progression free at 3 months. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) or clear worsening of evaluable disease or the appearance of any new lesions.

  six months from patient registration for bevacizumab naive patients, and 3 months from patient registration for patients with prior bevacizumab treatment

Secondary Outcomes (4)

• Overall Survival

  From date of registration to date of death due to any cause, up to 5 years.

• Mean Symptom Severity Score Between Responders and Non-responders at Baseline and by Cycle

  Baseline, and Cycles 1-6

• Mean Symptom Interference Score Between Responders and Non-responders at Baseline and by Cycle

  Baseline, and Cycles 1-6

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

  Date treatment consent signed to date off study, approximately 20 months and 18 days for the first Arm/Group, and 28 months and 23 days for the second Arm/Group.

Study Arms (2)

Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure

EXPERIMENTAL

Topotecan .25 mg and pazopanib 600 mg are administered orally daily until progression, up to one year.

Drug: topotecan; Drug: pazopanib

Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure

EXPERIMENTAL

Topotecan .25 mg and pazopanib 600 mg are administered orally daily until progression, up to one year.

Drug: topotecan; Drug: pazopanib

Interventions

topotecan DRUG

Taken .25 mg orally, daily continuous until progression up to one year.

Also known as: Hycamtin

Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure; Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure

pazopanib DRUG

600 mg orally, daily until progression, up to one year.

Also known as: Votrient

Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure; Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure

Eligibility Criteria

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

You may qualify if:

• Patients with histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM or GS is made. Patients must have evidence of progression of the GBM or GS on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Patient must have failed prior chemoradiation with temozolomide and any other therapies except BEV (group A), or must have failed primary chemoradiation and a BEV-incorporating treatment (group B).
• Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy). The intent therefore is that patients had no more than 3 prior therapies
• (initial and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse.
• For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse.
• Patients must be greater than 12 weeks following completion of chemoradiation or any additional radiation to reduce the chance of pseudoprogression.
• Measurable disease is required unless patient is post-operative and in that case patient can have no evidence of disease.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
• Archived tumor tissue must be available for all subjects for confirmation of the diagnosis before or during treatment. Samples must be provided within 4 weeks of enrollment.
• Patients must be greater than or equal to 18 years old.
• Patients must have a Karnofsky performance status of greater than or equal to 60.
• At the time of registration: Patients must have recovered from the toxic effects of prior therapy: greater than or equal to 28 days from any investigational agent, greater than or equal to 28 days from prior cytotoxic therapy, greater than or equal to 14 days from vincristine, greater than or equal to 42 days from nitrosoureas, greater than or equal to 21 days from procarbazine administration, \>21 days from bevacizumab administration and greater than or equal to 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of noncytotoxic agents should be directed to Academic Principal Investigator (PI).
• Patients must have adequate organ function:
• Bone marrow function (White blood cell (WBC) greater than or equal to 3,000/microl, absolute neutrophil count (ANC) greater than or equal to 1,500/mm\^3, platelet count of greater than or equal to 100,000/mm\^3, and hemoglobin greater than or equal to 10 gm/dl).
• Eligibility level for hemoglobin may be reached by transfusion.
• Liver function (alanine amino transferase (ALT) and aspartate aminotransferase (AST) \< 2.5 X upper limit of normal (ULN), and total bilirubin \< 1.5 X ULN), prothrombin time (PT) or international normalized ratio (INR), and activated partial thromboplastin time (aPTT) less than or equal to 1.2 X ULN.

You may not qualify if:

• Patients must not have any significant medical illnesses that in the investigators opinion cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this therapy.
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease.
• Known intraluminal metastatic lesion/s with risk of bleeding.
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel.
• Presence of uncontrolled infection.
• Corrected QT interval (QTc) \> 480 msecs using Bazett's formula. Bazett's Formula: QTc (Bazett)=QT/RR
• History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Macdonald D, Cairncross G, Stewart D, Forsyth P, Sawka C, Wainman N, Eisenhauer E. Phase II study of topotecan in patients with recurrent malignant glioma. National Clinical Institute of Canada Clinical Trials Group. Ann Oncol. 1996 Feb;7(2):205-7. doi: 10.1093/oxfordjournals.annonc.a010550.

  PMID: 8777179 BACKGROUND

• Armstrong TS, Mendoza T, Gning I, Coco C, Cohen MZ, Eriksen L, Hsu MA, Gilbert MR, Cleeland C. Validation of the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT). J Neurooncol. 2006 Oct;80(1):27-35. doi: 10.1007/s11060-006-9135-z. Epub 2006 Apr 6.

  PMID: 16598415 BACKGROUND

• Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007 Oct 20;25(30):4722-9. doi: 10.1200/JCO.2007.12.2440.

  PMID: 17947719 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Central Nervous System Neoplasms

Interventions

Topotecan; pazopanib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kevin Camphausen
• Organization: National Cancer Institute

camphauk@nih.gov

240-760-6205

Study Officials

• Kevin Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: August 29, 2013
• Study Start: December 10, 2015
• Primary Completion: September 12, 2019
• Study Completion: September 12, 2019
• Last Updated: August 11, 2025
• Results First Posted: September 18, 2020

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)