Central Nervous System (CNS) MetastasesPhase 2NCT01736800
Phase II Trial of Chemotherapy With Temodar With Topotecan for CNS Metastasis of Solid Tumors
A Phase 2 study testing Topotecan and Temozolomide in people with Central Nervous System (CNS) Metastases and Brain Metastases, run by The Methodist Hospital Research Institute at 2 sites in United States.
Trial summary
The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with Temozolomide and Topotecan in patients with CNS metastases of solid tumors. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years and will receive 8 cycles of chemotherapy. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Central Nervous System (CNS) Metastases, Brain Metastases
- What is being tested?
- Topotecan and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2007to Nov 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for the study, patients must have evidence of progressive CNS metastases of a solid tumor (new or progressing lesions), and either:
- Have failed prior WBRT.
- Or: not be candidates for surgical intervention and not require immediate radiation therapy to relieve symptoms, and have controlled systemic disease.
- Additional requirements:
- Patients must be > 18 years old.
- Patients must have radiographically measurable tumor on the updated scan within 2 weeks prior to starting treatment.
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- Patients must have histopathologic documentation of primary tumor at the time of initial diagnosis.
- Patients must be in adequate condition at time of enrollment, as indicated by:
- Absolute neutrophil count (ANC) greater than or equal 1,500/mm3
- Hemoglobin greater than or equal 9 gm/dL
- Platelets greater than or equal 100,000/mm3
- Karnofsky Performance Status greater than or equal 50
- Creatinine clearance >40 ml/min
- Total bilirubin less than or equal 2.0 mg/dl and SGOT, SGPT less than or equal 3 times upper limit of normal
- Patients must not be receiving concurrent anti-tumor therapy and must have recovered from toxicity of prior therapy. Minimum intervals required:
- greater than or equal 6 weeks after receiving nitrosourea cytotoxic drug
- greater than or equal 4 weeks after receiving any non-nitrosourea cytotoxic drug or any systemic investigational agent with exception of methotrexate
- greater than or equal 2 weeks after receiving methotrexate
- greater than or equal 2 weeks after receiving any non-cytotoxic anti-tumor drug.
- greater than or equal 4 weeks after radiation therapy or SRS.
- greater than or equal 3 weeks after craniotomy or other surgery.
- Female patients of childbearing potential must have a negative pregnancy test at the time of screening. All patients must be willing to practice an effective method of birth control during the study. Female patients must not be pregnant or breast-feeding during the entire study.
- Patients or legal representatives must understand the investigational nature of this study and sign a written informed consent form, approved by the Institutional Review Board (IRB) prior to enrolling into the study.
- No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
Who cannot join
- Patients who are pregnant or breastfeeding, or females of childbearing potential not using adequate contraception.
- Known allergy to temozolomide or topotecan.
- Severe vomiting or other inability to administer medications orally.
- Major medical illnesses or psychiatric impairment that in the investigator's opinion will prevent administration or completion of the protocol therapy and/or will interfere with follow-up.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Houston Methodist Hospital
Houston, Texas, 77030
Methodist Neurological Institute - Department of Neurosurgery
Houston, Texas, 77030
About this study
Official title: Phase II Trial of Chemotherapy With Temozolomide in Combination With Topotecan for Central Nervous System (CNS) Metastasis of Solid Tumors
The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with Temozolomide and Topotecan in patients with CNS metastases of solid tumors. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years and will receive 8 cycles of chemotherapy. The primary endpoint is the determinant median overall survival and progression-free survival of this regimen, time to progression of the brain metastases, and assessment of toxicity levels in this regimen.
Read the detailed description
The long-term objective of this research project is to develop chemotherapy-based approach to the treatment of brain metastases. The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with temozolomide and topotecan in patients with central nervous system (CNS) metastases of solid tumors. Patients with brain metastases of solid tumors have a poor prognosis, despite improvements in survival achieved with modern neurosurgical and radiation techniques. Chemotherapy does not play any significant role in this disease, but may have application in salvage of patients who have failed radiation therapy. In patients who are not surgical candidates, do not require immediate XRT to relieve symptoms and have controlled systemic disease, effective chemotherapy as an alternative to XRT might decrease the risk of radiation induced neurotoxicity.
Recent advances in treatment of systemic disease with the use of modern chemotherapy and pathobiologic agents have significantly improved overall survival of cancer patients, putting them at risk for CNS metastases and radiation induced neurotoxicity. Both, temozolomide and topotecan have good blood-brain barrier penetration and have shown activity in CNS malignancies. Preclinical studies suggest synergy of this drug combination. This is a single-arm, open-label phase II drug study. All patients will receive the chemotherapy combination. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years. Patients will receive up to 8 cycles of chemotherapy. The primary endpoint is the rate of radiologic response of brain metastases and secondary endpoints are median overall survival, progression-free survival, time to progression of brain metastases and toxicity. The study is expected to provide data to be used in generating further research hypotheses.
- Being tested
- Topotecan, Temozolomide
- Keywords
- Temozolomide, Topotecan, Central Nervous System Metastases, Chemotherapy, Brain Metastases, Solid Tumors
- Medical subject headings
- Neoplasm Metastasis, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopotecanDrug
Also called Hycamtin
Patients will receive Topotecan intravenous treatment days 2-6 of each 28-day cycle at The Mehthodist Hospital Outpatient Infusion Center.
TemozolomideDrug
Also called Temodar
Temozolomide is taken on an empty stomach at night and should not be chewed. Patients receive Temozolomide on days 1-5 of a 28-day schedule.
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide/Topotecan | Experimental | Temozolomide pills are to be taken on an empty stomach at night and should not be chewed. Patients receive Temozolomide on days 1-5 of a 28-day schedule. Patients will receive Topotecan intravenous treatment days 2-6 of each 28-day cycle at The Mehthodist Hospital Outpatient Infusion Center. Receives: Drug: Topotecan; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiologic Response
The primary objective of this study is to determine the overall rate of radiologic response of brain metastases to combination chemotherapy with temozolomide and topotecan in patients with CNS metastases of solid tumors
Measured: 5 years
Secondary outcomes (1)
Median Overall Survival
Secondary objectives are to determine median overall survival and progression-free survival on this regimen, to determine time to progression of the brain metastases, and to assess toxicity of this regimen
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2012 (estimated)
- Study startMar 2007
- Primary completionNov 2014
- Study completionNov 2014
Why it stopped: No enrollment and PI requested study termination per IRB system.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System (CNS) MetastasesStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pamela Z New, M.D., Principal investigator, Methodist Neurological Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01736800
- Sponsor's protocol ID
- Pro00000771
- Status last verified
- Sep 2017
- First submitted
- 19 Nov 2012
- Last updated
- 19 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Chemotherapy With Temozolomide in Combination With Topotecan for Central Nervous System (CNS) Metastasis of Solid Tumors
- ClinicalTrials.gov ID
- NCT01736800
- Acronym / sponsor ID
- Pro00000771
- Keywords
- Temozolomide, Topotecan, Central Nervous System Metastases, Chemotherapy, Brain Metastases, Solid Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No enrollment and PI requested study termination per IRB system.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- Mar 2007 (actual)
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 29 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with Temozolomide and Topotecan in patients with CNS metastases of solid tumors. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years and will receive 8 cycles of chemotherapy. The primary endpoint is the determinant median overall survival and progression-free survival of this regimen, time to progression of the brain metastases, and assessment of toxicity levels in this regimen.
Detailed description
The long-term objective of this research project is to develop chemotherapy-based approach to the treatment of brain metastases. The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with temozolomide and topotecan in patients with central nervous system (CNS) metastases of solid tumors. Patients with brain metastases of solid tumors have a poor prognosis, despite improvements in survival achieved with modern neurosurgical and radiation techniques. Chemotherapy does not play any significant role in this disease, but may have application in salvage of patients who have failed radiation therapy. In patients who are not surgical candidates, do not require immediate XRT to relieve symptoms and have controlled systemic disease, effective chemotherapy as an alternative to XRT might decrease the risk of radiation induced neurotoxicity.
Recent advances in treatment of systemic disease with the use of modern chemotherapy and pathobiologic agents have significantly improved overall survival of cancer patients, putting them at risk for CNS metastases and radiation induced neurotoxicity. Both, temozolomide and topotecan have good blood-brain barrier penetration and have shown activity in CNS malignancies. Preclinical studies suggest synergy of this drug combination. This is a single-arm, open-label phase II drug study. All patients will receive the chemotherapy combination. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years. Patients will receive up to 8 cycles of chemotherapy. The primary endpoint is the rate of radiologic response of brain metastases and secondary endpoints are median overall survival, progression-free survival, time to progression of brain metastases and toxicity. The study is expected to provide data to be used in generating further research hypotheses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temozolomide/Topotecan | Experimental | Drug: Topotecan, Drug: TemozolomideTemozolomide pills are to be taken on an empty stomach at night and should not be chewed. Patients receive Temozolomide on days 1-5 of a 28-day schedule. Patients will receive Topotecan intravenous treatment days 2-6 of each 28-day cycle at The Mehthodist Hospital Outpatient Infusion Center. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- To be eligible for the study, patients must have evidence of progressive CNS metastases of a solid tumor (new or progressing lesions), and either:
- Have failed prior WBRT.
- Or: not be candidates for surgical intervention and not require immediate radiation therapy to relieve symptoms, and have controlled systemic disease.
- Patients must be > 18 years old.
- Patients must have radiographically measurable tumor on the updated scan within 2 weeks prior to starting treatment.
Key exclusion criteria (4 listed)
- Patients who are pregnant or breastfeeding, or females of childbearing potential not using adequate contraception.
- Known allergy to temozolomide or topotecan.
- Severe vomiting or other inability to administer medications orally.
- Major medical illnesses or psychiatric impairment that in the investigator's opinion will prevent administration or completion of the protocol therapy and/or will interfere with follow-up.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TopotecanAlso: HycamtinPatients will receive Topotecan intravenous treatment days 2-6 of each 28-day cycle at The Mehthodist Hospital Outpatient Infusion Center. | Drug | Temozolomide/Topotecan |
| TemozolomideAlso: TemodarTemozolomide is taken on an empty stomach at night and should not be chewed. Patients receive Temozolomide on days 1-5 of a 28-day schedule. | Drug | Temozolomide/Topotecan |
Primary outcome
Radiologic Response
Time frame: 5 years
The primary objective of this study is to determine the overall rate of radiologic response of brain metastases to combination chemotherapy with temozolomide and topotecan in patients with CNS metastases of solid tumors
1 secondary outcome
Median Overall Survival
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2017.
- PO 5200Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pamela Z New, M.D. principal investigator
Methodist Neurological Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topotecan and Temozolomide in people with Central Nervous System (CNS) Metastases and Brain Metastases, run by The Methodist Hospital Research Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiologic Response (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2017; AzTrials last refreshed its copy on 7 Nov 2026.