Gynecologic TumorsPhase 1NCT00800345
Phase I Trial of Oral Metronomic Topotecan and Oral Pazopanib to Treat Recurrent/Persistent Gynecologic Tumors
A Phase 1 study testing Oral Topotecan and Pazopanib in people with Gynecologic Tumors, run by Vector Oncology at 1 site in United States.
Trial summary
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Gynecologic Tumors
- What is being tested?
- Oral Topotecan and Pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Sep 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must provide written informed consent prior to the performance of study specific procedures, and must be willing to comply with treatment and follow-up.
- Female patients, greater than 18 years of age with a histologically confirmed recurrent/persistent gynecologic malignancy.
- For patients with recurrent/persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: persistent disease = progression during primary platinum therapy; recurrent disease = disease that recurs ≤ 12 months after discontinuing primary platinum therapy; if disease recurrence occurs > 12 months after discontinuing primary platinum therapy, there must be progression either during a 2nd platinum therapy or < 6 months after discontinuing the 2nd platinum therapy.
- For patients with other gynecologic malignancies:
- Malignancy is metastatic or unresectable and no curative or palliative measures exist or are no longer effective.
- Maximum of two total prior treatments (this includes neoadjuvant, adjuvant, and metastatic settings) for the recurrent or persistent gynecologic tumors including chemotherapy, hormonal therapy, investigational therapy, radiation therapy, etc.)
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- Disease may be measurable or non-measurable according to RECIST version 1.0
- Gynecologic Oncology Group (GOG) performance status of 0,1,or 2
- Must have a life expectancy of at least six months
- Adequate bone marrow, liver, renal, and cardiac function at study entry as assessed by the following:
- Hemoglobin > 9.0 g/dL.
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
- Platelet count ≥ 100 x 10^9/L.
- Prothrombin time (PT) or international normalized ratio (INR) < 1.2 x upper limit of normal (ULN).
- Partial thromboplastin time (PTT) < 1.2 x ULN.
- Total bilirubin ≤ 1.5 x ULN.
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN.
- Creatinine ≤ 1.5 mg/dL or if serum creatinine is greater than 1.5 mg/dL, calculated creatinine clearance must be > 50 mL/min
- Urine dipstick for protein < 2+ or urine protein creatinine (UPC) ratio < 1.0.
- Left ventricular ejection fraction (LVEF) ≥ 50% or the institutional lower limit of normal (LLN)
- Patients must be physiologically incapable of becoming pregnant, be postmenopausal, or have a negative pregnancy test and agree to use adequate contraception.
Who cannot join
- Treatment naive patients.
- Repetitive or prolonged neutropenia or thrombocytopenia during previous therapy.
- Concurrent malignancy other than malignancies under study. Subjects who have had another malignancy and have been disease free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- Prior radiation therapy.
- Myelosuppressive chemotherapy within the past 28 days or has not recovered from the myelosuppressive effects of recent chemotherapy.
- Use of an investigational agent, including an investigational anti-cancer agent, immunotherapy, biological therapy, or hormonal therapy within 28 days prior to the first dose of study treatment.
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- Prior major surgery or trauma within 28 days prior to the first dose of study treatment and/or presence of any non-healing wound, fracture, or ulcer.
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis.
- Inability to swallow a capsule or clinically significant gastrointestinal abnormalities including, but not limited to:
- Malabsorption syndrome
- Major resection of the stomach or small bowel that could affect the absorption of study treatment
- Active peptic ulcer disease
- Inflammatory bowel disease
- Ulcerative colitis, 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.
- Unresolved bowel obstruction or diarrhea ≥ Grade 1
- Known intraluminal metastatic lesion(s) with risk of bleeding
- Known endobronchial lesions or involvement of large pulmonary vessels by tumor.
- Presence of uncontrolled infection.
- Prolongation of corrected QT interval > 480 milliseconds.
- History of any one or more of the following cardiovascular conditions within the past 6 months:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Coronary artery bypass graft
- Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- Poorly controlled hypertension (defined as systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
- History of cerebrovascular accident, transient ischemic attack, pulmonary embolism, or insufficiently treated deep vein thrombosis (DVT) within the past 6 months. Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
- Evidence of active bleeding or bleeding diathesis.
- Recent hemoptysis in excess of 2.5 mL within 8 weeks of 1st dose of study treatment.
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- Use of any prohibited medication within 14 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study treatment and during the study.
- Prior use of any investigational or licensed anti-angiogenic agent, including topotecan, bevacizumab, thalidomide, and agents that target vascular endothelial growth factor (VEGF), VEGF receptors, or platelet-derived growth factor (PDGF).
- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia.
- Known hypersensitivity to topoisomerase I inhibitors or pazopanib.
- Administration of any non-oncologic investigational drug within 30 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of Oral Metronomic Topotecan in Combination With Oral Pazopanib Utilizing a Daily Dosing Schedule to Treat Recurrent or Persistent Gynecologic Tumors
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors.
Read the detailed description
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors. The study will include a Screening Phase, a Treatment Phase and a Followup Phase. In the Screening Phase the subject's eligibility for study participation will be determined; this phase can last up to 28 days. The Treatment Phase will begin when the subject starts study treatment and will continue until the subject is removed from study treatment. The Follow-up Phase will last for 30 days after the subject ends study treatment. The study will be conducted at approximately 1 site. Treatment cycle length is 28 days. Radiologic imaging will be repeated after every 2 cycles of treatment.
- Conditions
- Gynecologic Tumors
- Being tested
- Oral Topotecan, Pazopanib
- Keywords
- Gynecologic tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral TopotecanDrug
Also called Hycamtin capsules
Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
PazopanibDrug
Also called GW786034, Votrient
Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
| Study group | Role | What they receive |
|---|---|---|
| Experimenal | Experimental | Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level. Receives: Drug: Oral Topotecan; Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Measured: Cycle 1 (28 days)
Secondary outcomes (1)
Treatment Response
Treatment response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
Measured: After every 2 cycles of treatment beginning on Cycle 1 Day 1, up to 38 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2008 (estimated)
- Study startApr 2009
- Primary completionJun 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gynecologic TumorsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vector Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Todd D Tillmanns, MD, Principal investigator, The West Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00800345
- Sponsor's protocol ID
- ATDTRPST0802
- Status last verified
- Dec 2016
- First submitted
- 1 Dec 2008
- Last updated
- 28 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Oral Metronomic Topotecan in Combination With Oral Pazopanib Utilizing a Daily Dosing Schedule to Treat Recurrent or Persistent Gynecologic Tumors
- ClinicalTrials.gov ID
- NCT00800345
- Acronym / sponsor ID
- ATDTRPST0802
- Conditions
- Gynecologic Tumors
- Keywords
- Gynecologic tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Vector OncologyUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Apr 2009
- Primary completion
- Jun 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 2 Dec 2008 (estimated)
- Results
- Posted 23 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors.
Detailed description
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors. The study will include a Screening Phase, a Treatment Phase and a Followup Phase. In the Screening Phase the subject's eligibility for study participation will be determined; this phase can last up to 28 days. The Treatment Phase will begin when the subject starts study treatment and will continue until the subject is removed from study treatment. The Follow-up Phase will last for 30 days after the subject ends study treatment. The study will be conducted at approximately 1 site. Treatment cycle length is 28 days. Radiologic imaging will be repeated after every 2 cycles of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimenal | Experimental | Drug: Oral Topotecan, Drug: PazopanibMetronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for dose limiting toxicity (DLT) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Subjects must provide written informed consent prior to the performance of study specific procedures, and must be willing to comply with treatment and follow-up.
- Female patients, greater than 18 years of age with a histologically confirmed recurrent/persistent gynecologic malignancy.
- For patients with recurrent/persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: persistent disease = progression during primary platinum therapy; recurrent disease = disease that recurs ≤ 12 months after discontinuing primary platinum therapy; if disease recurrence occurs > 12 months after discontinuing primary platinum therapy, there must be progression either during a 2nd platinum therapy or < 6 months after discontinuing the 2nd platinum therapy.
- For patients with other gynecologic malignancies:
- Disease may be measurable or non-measurable according to RECIST version 1.0
Key exclusion criteria (37 listed)
- Treatment naive patients.
- Repetitive or prolonged neutropenia or thrombocytopenia during previous therapy.
- Concurrent malignancy other than malignancies under study. Subjects who have had another malignancy and have been disease free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- Prior radiation therapy.
- Myelosuppressive chemotherapy within the past 28 days or has not recovered from the myelosuppressive effects of recent chemotherapy.
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 |
|---|---|---|
| Oral TopotecanAlso: Hycamtin capsulesStarting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth. | Drug | Experimenal |
| PazopanibAlso: GW786034, VotrientStarting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth. | Drug | Experimenal |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: Cycle 1 (28 days)
1 secondary outcome
Treatment Response
Time frame: After every 2 cycles of treatment beginning on Cycle 1 Day 1, up to 38 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Todd D Tillmanns, MD principal investigator
The West Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oral Topotecan and Pazopanib in people with Gynecologic Tumors, run by Vector Oncology at 1 site 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 21 inclusion and 37 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: finished, as of the sponsor's last update on 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Dose Limiting Toxicity (DLT) (time frame: Cycle 1 (28 days)). 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 28 Mar 2017.