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Kidney CancerPhase 1PTK/RADNCT00303732

Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors

A Phase 1 study testing RAD001 (everolimus) and PTK787 (vatalanib) in people with Kidney Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by Daniel George, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Vatalanib and everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib and everolimus and to see how well they work in treating patients… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RAD001 (everolimus) and PTK787 (vatalanib)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteUnited States
Study dates
Dec 2004to Aug 2012
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor with radiographic evidence of metastatic disease
  • No standard therapy exists (phase I)
  • Unresectable or metastatic renal cell carcinoma (phase Ib)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • AST or ALT ≤ 2.5 times upper limit of normal (ULN)
  • Total cholesterol < 300 mg/dL
  • Triglycerides < 350 mg/dL
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance > 40 mL/min
  • Negative proteinuria by dip stick OR total urinary protein ≤ 500 mg
  • No uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with antihypertensive regimen
  • No unstable angina pectoris
  • No symptomatic congestive heart failure (New York Heart Association class III or IV heart disease)
  • No uncontrolled serious cardiac arrhythmia (symptomatic supraventricular tachycardia or any ventricular tachycardia/fibrillation)
  • No myocardial infarction in the past 6 months
  • No uncontrolled diabetes
  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • No active or uncontrolled infection
  • No uncontrolled hyperlipidemia
  • No chronic renal disease
  • No acute or chronic liver disease (e.g., hepatitis or cirrhosis)
  • No impaired gastrointestinal (GI) function OR GI disease that may significantly alter the absorption of vatalanib or everolimus, including any of the following:
  • Ulcerative disease
  • Uncontrolled nausea and vomiting with solid food
  • Watery diarrhea > 5 times daily
  • Malabsorption syndrome
  • Bowel obstruction
  • Inability to swallow the tablets
  • No confirmed HIV infection
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent severe and/or uncontrolled medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

  • Recovered from prior therapy
  • No prior antivascular endothelial growth factor therapy
  • More than 4 weeks since prior major surgery* (laparotomy)
  • More than 2 weeks since prior minor surgery*
  • More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
  • More than 6 weeks since prior antibody therapy
  • More than 2 weeks since prior biologic/immunotherapy
  • More than 2 weeks since prior limited-field radiotherapy
  • More than 4 weeks since prior full-field radiotherapy
  • More than 4 weeks since prior investigational agents
  • Prior transfusions allowed provided blood counts are stable for > 2 weeks
  • Concurrent epoetin alfa allowed
  • No concurrent warfarin or similar oral anticoagulants that are metabolized by the cytochrome P450 system
  • Heparin and low molecular weight heparin allowed NOTE: *Insertion of a vascular access device is not considered major or minor surgery

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: PTK787/ZK222584 and RAD001 for Patients With Advanced Solid Tumors

RATIONALE: Vatalanib and everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib and everolimus and to see how well they work in treating patients with advanced solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) of vatalanib and everolimus in patients with advanced solid tumors.
  • Determine the safety and tolerability of vatalanib and everolimus in patients with advanced solid tumors.
  • Evaluate the safety and tolerability of vatalanib and everolimus at the MTD in patients with metastatic renal cell carcinoma (RCC).

Secondary

  • Describe the non dose-limiting toxic effects associated with vatalanib and everolimus.
  • Describe the pharmacokinetics of vatalanib and everolimus in patients with advanced solid tumors.
  • Determine the functional extent of mTOR inhibition by changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells in patients treated with vatalanib and everolimus.
  • Describe any clinical responses seen in patients with metastatic RCC in a dose-expansion cohort treated at the MTD.
  • Observe overall survival of RCC patients treated with vatalanib and everolimus.
  • Determine the time to progression of patients with RCC treated with vatalanib and everolimus.

OUTLINE: This is a phase I dose-escalation study followed by a phase Ib study.

  • Phase I (solid tumors): Patients receive oral vatalanib on days 1-28 and oral everolimus on days 15-28 during course 1 and on days 1-28 during all subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vatalanib and everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase Ib (renal cell carcinoma only): Patients receive oral vatalanib and oral everolimus at the MTD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Being tested
RAD001 (everolimus), PTK787 (vatalanib)
Keywords
unspecified adult solid tumor, protocol specific, recurrent renal cell cancer, stage IV renal cell cancer
Medical subject headings
Kidney Neoplasms, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RAD001 (everolimus)Drug

    Also called Afinitor

  • PTK787 (vatalanib)Drug

Study groups in NCT00303732
Study groupRoleWhat they receive
PTK787, RAD001ExperimentalPTK787 (vatalinib) 1000 mg daily, RAD001 (everolimus) 5 mg daily
Receives: Drug: RAD001 (everolimus); Drug: PTK787 (vatalanib)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) of vatalanib and everolimus

    Patients were evaluated on Day 1,14 and 28 for dose limiting toxicities

    Measured: Day 1 - 28

  2. Safety and tolerability

    Adverse events were assessed every 14 days for the length of the treatment period.

    Measured: Duration of study treatment

  3. Safety and tolerability at the MTD in patients with metastatic renal cell carcinoma (RCC)

    Patients were assessed for adverse events every 14 days while on study treatment

    Measured: Duration of study treatment

Secondary outcomes (6)
  1. Non dose-limiting toxicity

    Patients were assessed every 14 days for non dose-limiting toxicity while on study treatment

    Measured: Duration of study treatment

  2. Pharmacokinetics

    Blood was drawn for PK assessment on Day 14 of Cycle 1 and Day 1 of Cycle 2

    Measured: Day 14 Cycle 1, Day 1 Cycle 2

  3. Changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells

    Samples were collected on Day 1 and at Day 28 of Cycle 1

    Measured: Day 1 and 28

  4. Clinical response in patients with metastatic RCC

    patients underwent restaging studies every 2 cycles while on treatment for evidence of disease response

    Measured: Duration of treatment

  5. Overall survival of patients with RCC

    Measured: Until death

  6. Time to progression of patients with RCC

    Patients were followed for evidence of disease progression as long as they remained on study drug.

    Measured: Duration of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2006 (estimated)
  2. Study startDec 2004
  3. Primary completionAug 2010
  4. Study completionAug 2012

Resources

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
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00303732
Sponsor's protocol ID
Pro00012347
Other IDs
DUMC-6626-04-12R0, CDR0000454988
Acronym
PTK/RAD
Status last verified
Mar 2016
First submitted
15 Mar 2006
Last updated
3 Mar 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Speca JC, Mears AL, Creel PA, et al.: Phase I study of PTK787/ZK222584 (PTK/ZK) and RAD001 for patients with advanced solid tumors and dose expansion in renal cell carcinoma patients. [Abstract] J Clin Oncol 25 (Suppl 18): A-5039, 244s, 2007.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RAD001 (everolimus) and PTK787 (vatalanib) in people with Kidney Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by Daniel George, MD 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?

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 3 Mar 2016. 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.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of vatalanib and everolimus (time frame: Day 1 - 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00303732, which also lists 1 linked publication.

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 3 Mar 2016.

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