Breast CancerPhase 1NCT00001944
Vinorelbine and XR9576 to Treat Cancer
A Phase 1 study testing Vinorelbine and XR9576 in people with Breast Cancer and Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Tumor resistance to anti-cancer drugs is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps chemotherapy drugs out of the cells, reducing treatment effectiveness. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Breast Cancer, Cancer, Lung Cancer
- What is being tested?
- Vinorelbine and XR9576
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1999to Jun 2001
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Age greater than or equal to 18 years.
Histologic or cytologic confirmation of cancer, for which there is no known standard therapy capable of extending life expectancy.
Performance status ECOG 0-2.
Life expectancy of 3 months or greater.
Platelet count greater than or equal to 90,000/mL.
Absolute granulocyte count (AGC) greater than or equal to 1,000/mL.
Serum creatinine less than or equal to 1.5 mg/dl (or if greater than 1.5, measured creatinine clearance greater than or equal to 50 mL/min).
SGPT and SGOT less than or equal to 2.5 times normal limit, and bilirubin less than or equal to 1.5 times normal limit (in patients with clinical evidence of Gilbert's disease, less than or equal to 3 times normal limit).
2 weeks from prior radiation or chemotherapy and recovery from associated toxicities such that they meet eligibility criteria. Hormonal therapy may be taken up to the time of enrollment.
No serious intercurrent medical illness.
Bidimensionally measurable disease by radiographic means or physical examination; or relevant tumor markers (i.e. CA-125 and PSA greater than or equal to 2 times upper limit of normal).
The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol.
No pregnant or nursing women; or women of childbearing potential unless using effective contraception as determined by the patient's physician.
No history of another malignancy; specifically, no patients with a non-skin malignancy or with melanoma within the past 5 years; no concomitant malignancy that has not been curatively treated. However, cancer survivors who have undergone potentially curative therapy for a prior malignancy at least 5 years before enrollment is considered, and are deemed at low risk for recurrence by their treating physicians.
No patients with current or a history of CNS metastases.
No patients who are a poor medical risk because of other non malignant systemic disease or active, uncontrolled infection.
No HIV seropositive patients.
No prior vinorelbine therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: A Clinical Trial of the P-Glycoprotein Antagonist, XR9576, in Combination With Vinorelbine in Patients With Cancer: Analysis of the Interaction Between XR9576 and Vinorelbine
Tumor resistance to anti-cancer drugs is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps chemotherapy drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called XR9576, has blocked pumping by this protein. It is being used in this study to try to increase the amount of the anti-cancer drug vinorelbine, in cancer cells. Vinorelbine has been shown in several clinical trials to be effective against some advanced cancers, including breast, lung and ovarian, and is one of the drugs pumped out of tumor cells by P-glycoprotein.
Patients with cancer 18 years and older may be eligible for this study. Candidates will be screened with tests that may include blood and urine tests, electrocardiogram, echocardiogram, CT scans, X-rays, and nuclear medicine studies. A tumor biopsy may be done for diagnostic or research purposes.
Read more
Study participants will undergo tumor imaging with the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures are taken with a gamma camera. After this baseline scan, patients will receive a dose of XR9576 and undergo a second scan 24 hours later. The scan will show whether XR9576 affects the accumulation and elimination of Sestamibi in tumor cells. This procedure may provide a way to monitor cancers for evidence of chemotherapy resistance and show if XR9576 can improve the effectiveness of therapy.
At least 10 days after the baseline and XR9576 scans, patients will begin the first of 3 or more 21-day cycles of vinorelbine treatment. On days 1 and 8 of each cycle, patients will receive a 30-minute infusion of XR9576 intravenously (through a vein) followed by vinorelbine, infused over a 6- to 10-minute period. (In some patients, XR9576 will be administered before only one of the two vinorelbine dosages.)
Physical examination, blood tests, and other procedures may be done periodically to monitor treatment.
Read the detailed description
Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer. Accumulating evidence indicates that in some malignancies P-glycoprotein can confer resistance, and that its reversal can improve therapeutic outcome. Clinical trials investigating P-glycoprotein antagonists have been hampered by the occurrence of unpredictable pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic agents to avert excessive toxicity. XR9576 is a new P-glycoprotein antagonist that is more potent, has prolonged activity, and is potentially devoid of significant pharmacokinetic interactions. This phase I study seeks to identify the safety of XR9576 administration in combination with vinorelbine and determine the extent, if any, of a pharmacokinetic interaction between these two drugs. Clinical responses will also be determined.
- Conditions
- Breast Cancer, Cancer, Lung Cancer, Ovarian Cancer
- Being tested
- Vinorelbine, XR9576
- Keywords
- Drug Resistance, MDR-1, P-Glycoprotein Blocker, Pgp, Resistance Reversal
- Medical subject headings
- Breast Neoplasms, Neoplasms, Lung Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinorelbineDrug
XR9576Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startDec 1999
- Study completionJun 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001944
- Sponsor's protocol ID
- 000044
- Other IDs
- 00-C-0044
- Status last verified
- Dec 2000
- First submitted
- 18 Jan 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol. 1974 Feb;83(1):103-16. doi: 10.1002/jcp.1040830114. No abstract available.
PubMed 4855907Beck WT, Cirtain MC, Lefko JL. Energy-dependent reduced drug binding as a mechanism of Vinca alkaloid resistance in human leukemic lymphoblasts. Mol Pharmacol. 1983 Nov;24(3):485-92.
PubMed 6579344Fairchild CR, Ivy SP, Kao-Shan CS, Whang-Peng J, Rosen N, Israel MA, Melera PW, Cowan KH, Goldsmith ME. Isolation of amplified and overexpressed DNA sequences from adriamycin-resistant human breast cancer cells. Cancer Res. 1987 Oct 1;47(19):5141-8.
PubMed 2441861
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial of the P-Glycoprotein Antagonist, XR9576, in Combination With Vinorelbine in Patients With Cancer: Analysis of the Interaction Between XR9576 and Vinorelbine
- ClinicalTrials.gov ID
- NCT00001944
- Acronym / sponsor ID
- 000044
- Conditions
- Breast Cancer, Cancer, Lung Cancer, Ovarian Cancer
- Keywords
- Drug Resistance, MDR-1, P-Glycoprotein Blocker, Pgp, Resistance Reversal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 1999
- Study completion
- Jun 2001
- First posted
- 10 Dec 2002 (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.
Tumor resistance to anti-cancer drugs is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps chemotherapy drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called XR9576, has blocked pumping by this protein. It is being used in this study to try to increase the amount of the anti-cancer drug vinorelbine, in cancer cells. Vinorelbine has been shown in several clinical trials to be effective against some advanced cancers, including breast, lung and ovarian, and is one of the drugs pumped out of tumor cells by P-glycoprotein.
Patients with cancer 18 years and older may be eligible for this study. Candidates will be screened with tests that may include blood and urine tests, electrocardiogram, echocardiogram, CT scans, X-rays, and nuclear medicine studies. A tumor biopsy may be done for diagnostic or research purposes.
Study participants will undergo tumor imaging with the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures are taken with a gamma camera. After this baseline scan, patients will receive a dose of XR9576 and undergo a second scan 24 hours later. The scan will show whether XR9576 affects the accumulation and elimination of Sestamibi in tumor cells. This procedure may provide a way to monitor cancers for evidence of chemotherapy resistance and show if XR9576 can improve the effectiveness of therapy.
At least 10 days after the baseline and XR9576 scans, patients will begin the first of 3 or more 21-day cycles of vinorelbine treatment. On days 1 and 8 of each cycle, patients will receive a 30-minute infusion of XR9576 intravenously (through a vein) followed by vinorelbine, infused over a 6- to 10-minute period. (In some patients, XR9576 will be administered before only one of the two vinorelbine dosages.)
Physical examination, blood tests, and other procedures may be done periodically to monitor treatment.
Detailed description
Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer. Accumulating evidence indicates that in some malignancies P-glycoprotein can confer resistance, and that its reversal can improve therapeutic outcome. Clinical trials investigating P-glycoprotein antagonists have been hampered by the occurrence of unpredictable pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic agents to avert excessive toxicity. XR9576 is a new P-glycoprotein antagonist that is more potent, has prolonged activity, and is potentially devoid of significant pharmacokinetic interactions. This phase I study seeks to identify the safety of XR9576 administration in combination with vinorelbine and determine the extent, if any, of a pharmacokinetic interaction between these two drugs. Clinical responses will also be determined.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| Vinorelbine | Drug | – |
| XR9576 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 4855907Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol. 1974 Feb;83(1):103-16. doi: 10.1002/jcp.1040830114. No abstract available.
- Background: PubMed 6579344Beck WT, Cirtain MC, Lefko JL. Energy-dependent reduced drug binding as a mechanism of Vinca alkaloid resistance in human leukemic lymphoblasts. Mol Pharmacol. 1983 Nov;24(3):485-92.
- Background: PubMed 2441861Fairchild CR, Ivy SP, Kao-Shan CS, Whang-Peng J, Rosen N, Israel MA, Melera PW, Cowan KH, Goldsmith ME. Isolation of amplified and overexpressed DNA sequences from adriamycin-resistant human breast cancer cells. Cancer Res. 1987 Oct 1;47(19):5141-8.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Vinorelbine and XR9576 in people with Breast Cancer and Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001944, which also lists 3 linked publications.
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 4 Mar 2008.