Kidney NeoplasmsPhase 1NCT00001570
A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer
A Phase 1 study testing PSC 833 and vinblastine in people with Kidney Neoplasms and Neoplasm Metastasis, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Kidney Neoplasms, Neoplasm Metastasis
- What is being tested?
- PSC 833 and vinblastine
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 1997to Jan 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
DISEASE CHARACTERISTICS:
Histologically proven renal cancer with clear cell component:
Measurable or evaluable disease;
No brain metastases;
No grade 2 or greater peripheral neuropathy or neurologic toxicity symptoms.
PRIOR/CONCURRENT THERAPY:
Biologic Therapy: Not specified.
Chemotherapy: No prior or concurrent hypersensitivity to PSC 833 or cyclosporine A.
Endocrine Therapy: Not specified.
Radiotherapy: No prior radiation therapy within 4 weeks of study.
Surgery: No major surgery within 4 weeks of study.
Other: No concurrent treatments that interfere with cyclosporine blood concentrations.
PATIENT CHARACTERISTICS:
Age: 18 and over.
Performance Status: ECOG 0-2.
Life Expectancy: At least 16 weeks.
Hematopoietic:
ANC greater than or equal to 1500/mm(3);
Platelet count greater than or equal to 100,000/mm(3).
Hepatic:
Bilirubin no greater than 1.5 x normal;
AST no greater than 2.5 x normal.
Renal:
Creatinine no greater than 2.0 mg/dL OR;
Creatinine clearance greater than or equal to 50 mL/min.
Cardiovascular:
No concurrent angina or myocardial infarction that has not been appropriately treated.
Other:
Not pregnant or nursing.
Effective contraceptive required of all fertile patients.
Patients with a history of curatively treated basal cell or squamous cell carcinoma are eligible.
No HIV seropositivity.
No chronic hepatitis or cirrhosis.
Patients with concurrent reversible conditions such as diabetes, hypercalcemia, hyperuricemia, hyperviscosity, infection, renal disease, or spinal cord compression are eligible with appropriate therapy.
Patients must give written informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. To ensure the safety of a 7 day infusion of PSC 833, one patient is treated for 5 days and a second for 6 days, before the first cohort is enrolled.
Vinblastine is administered in escalating doses on days 2-5. At least 3 patients are entered at each dose level. The MTD will be defined as the dose immediately below that at which 2 patients experience dose limiting toxicity.
Treatment continues every 28 days.
Read the detailed description
The Phase I clinical trial of the combination of 120-hour continuous intravenous infusion of vinblastine with oral PSC 833 has shown activity in patients with advanced malignancies, particularly renal cell cancer. The MTD of vinblastine in combination with the oral drink solution of PSC 833 was determined to be 0.9 mg/m2/day for five days and 12.5 mg/kg po q 12 hours for eight days, respectively. For the soft gel capsule formulation, the MTD was determined to be 0.6 mg/m2/day vinblastine for five days and 4 mg/kg po q 6 hours PSC 833 for eight days. Ataxia was the dose limiting toxicity. Of the 46 patients, two complete remissions and one partial remission were seen among 29 patients with renal cell carcinoma.
In this Phase I study, patients with advanced renal carcinoma will be treated with escalating doses of vinblastine given as a 72 hour infusion, starting at approximately 40% of the total standard dose. A shorter infusion schedule of vinblastine was chosen since there is evidence in other cytotoxic combinations that PSC 833 increases the AUC and decreases the plasma clearance of chemotherapeutic agents by approximately twofold. Cytochrome P 450 3A or CYP3A, which is the major cytochrome enzyme in the metabolism of vinblastine and PSC 833, will be measured during the first and fourth cycle through an in vivo test using a single intravenous dose of midazolam, a short-acting benzodiazepine. Vinblastine and PSC 833 pharmacokinetics will be performed at the same time. For patients with accessible lesions, tumor biopsy will be requested.
- Conditions
- Kidney Neoplasms, Neoplasm Metastasis
- Being tested
- PSC 833, vinblastine
- Keywords
- Cytochrome P 450, Multi-Drug Resistance, P-Glycoprotein, Pharmacokinetics
- Medical subject headings
- Kidney Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PSC 833Drug
vinblastineDrug
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 startFeb 1997
- Study completionJan 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 Kidney NeoplasmsStudies 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
- 46 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001570
- Sponsor's protocol ID
- 970074
- Other IDs
- 97-C-0074
- Status last verified
- Jan 2000
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Chapman AE, Goldstein LJ. Multiple drug resistance: biologic basis and clinical significance in renal-cell carcinoma. Semin Oncol. 1995 Feb;22(1):17-28. No abstract available.
PubMed 7855615Boote DJ, Dennis IF, Twentyman PR, Osborne RJ, Laburte C, Hensel S, Smyth JF, Brampton MH, Bleehen NM. Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J Clin Oncol. 1996 Feb;14(2):610-8. doi: 10.1200/JCO.1996.14.2.610.
PubMed 8636778Twentyman PR. MDR1 (P-glycoprotein) gene expression--implications for resistance modifier trials. J Natl Cancer Inst. 1992 Oct 7;84(19):1458-60. doi: 10.1093/jnci/84.19.1458. No abstract available.
PubMed 1359150
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 Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer
- ClinicalTrials.gov ID
- NCT00001570
- Acronym / sponsor ID
- 970074
- Conditions
- Kidney Neoplasms, Neoplasm Metastasis
- Keywords
- Cytochrome P 450, Multi-Drug Resistance, P-Glycoprotein, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 1997
- Study completion
- Jan 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.
Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. To ensure the safety of a 7 day infusion of PSC 833, one patient is treated for 5 days and a second for 6 days, before the first cohort is enrolled.
Vinblastine is administered in escalating doses on days 2-5. At least 3 patients are entered at each dose level. The MTD will be defined as the dose immediately below that at which 2 patients experience dose limiting toxicity.
Treatment continues every 28 days.
Detailed description
The Phase I clinical trial of the combination of 120-hour continuous intravenous infusion of vinblastine with oral PSC 833 has shown activity in patients with advanced malignancies, particularly renal cell cancer. The MTD of vinblastine in combination with the oral drink solution of PSC 833 was determined to be 0.9 mg/m2/day for five days and 12.5 mg/kg po q 12 hours for eight days, respectively. For the soft gel capsule formulation, the MTD was determined to be 0.6 mg/m2/day vinblastine for five days and 4 mg/kg po q 6 hours PSC 833 for eight days. Ataxia was the dose limiting toxicity. Of the 46 patients, two complete remissions and one partial remission were seen among 29 patients with renal cell carcinoma.
In this Phase I study, patients with advanced renal carcinoma will be treated with escalating doses of vinblastine given as a 72 hour infusion, starting at approximately 40% of the total standard dose. A shorter infusion schedule of vinblastine was chosen since there is evidence in other cytotoxic combinations that PSC 833 increases the AUC and decreases the plasma clearance of chemotherapeutic agents by approximately twofold. Cytochrome P 450 3A or CYP3A, which is the major cytochrome enzyme in the metabolism of vinblastine and PSC 833, will be measured during the first and fourth cycle through an in vivo test using a single intravenous dose of midazolam, a short-acting benzodiazepine. Vinblastine and PSC 833 pharmacokinetics will be performed at the same time. For patients with accessible lesions, tumor biopsy will be requested.
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 |
|---|---|---|
| PSC 833 | Drug | – |
| vinblastine | 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 7855615Chapman AE, Goldstein LJ. Multiple drug resistance: biologic basis and clinical significance in renal-cell carcinoma. Semin Oncol. 1995 Feb;22(1):17-28. No abstract available.
- Background: PubMed 8636778Boote DJ, Dennis IF, Twentyman PR, Osborne RJ, Laburte C, Hensel S, Smyth JF, Brampton MH, Bleehen NM. Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J Clin Oncol. 1996 Feb;14(2):610-8. doi: 10.1200/JCO.1996.14.2.610.
- Background: PubMed 1359150Twentyman PR. MDR1 (P-glycoprotein) gene expression--implications for resistance modifier trials. J Natl Cancer Inst. 1992 Oct 7;84(19):1458-60. doi: 10.1093/jnci/84.19.1458. No abstract available.
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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 PSC 833 and vinblastine in people with Kidney Neoplasms and Neoplasm Metastasis, 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 NCT00001570, 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.