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TumorsPhase 1NCT00402415

Study of Combination of Sirolimus and Sutent in Patients With Advanced Solid Tumors Non-Curable With Standard Therapy

A Phase 1 study testing Sunitinib malate and Rapamycin in people with Tumors, run by Yale University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

There are two drugs involved in this study. Sunitinib (Sutent(R)) is approved by the Food and Drug Administration (FDA) for the treatment of advanced renal cell (kidney) cancer and gastrointestinal stromal tumors. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tumors
What is being tested?
Sunitinib malate and Rapamycin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Feb 2006to Jul 2008
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

Who may be able to join

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients with previously untreated metastatic renal cell carcinoma are eligible.
  • Patients must have measurable disease by RECIST criteria.
  • Patients must have at least 1 lesion located in the neck, lung, solid organ (including liver) or soft tissue in abdomen or pelvis, or soft tissue in lower extremities that is 3 cm and ideally <7 cm in the transaxial plane. Larger lesions may be considered if they meet all other criteria. Index lesions must be well demarcated.
  • ECOG performance status of 0-1.
  • Must be ≥18 years of age.
  • Expected survival of at least 3 months.
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  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods. Pregnant and nursing patients are excluded because the effects of the combination of SU11248 (Sutent®) and sirolimus on a fetus or nursing child are unknown.
  • Must be able and willing to give written informed consent.
  • Patients must have the following clinical laboratory values: ANC count ≥1500/mm3; Platelets ≥100,000/mm3; Serum creatinine ≤2x upper limit of normal. If serum creatinine is above the upper limit of normal (but less than 2x normal), patients must have a measured 24 hour urine creatinine clearance ≥ 50 ml/min to be eligible; Total bilirubin < 1.5x upper limit of normal; Serum calcium < 12.0 mg/dl; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x the upper limit of normal; Prothrombin Time (PT), activated partial thromboplastin time (aPTT) and INR in the normal range;. Hemoglobin ≥9 gm/dl (may be corrected by transfusion).
  • Normal cardiac ejection fraction

Who cannot join

  • Diagnosis or history of central nervous system (CNS) disease (i.e. primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis).
  • Any active uncontrolled bleeding and any patient with a bleeding diathesis (for example, active peptic ulcer disease). Any grade 3 hemorrhage within 4 weeks prior to starting treatment.
  • Any ongoing coagulopathies or receiving anticoagulants.
  • Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy).
  • QTc interval > 500 msec on baseline EKG.
  • Cardiac ejection fraction below institutional lower limit of normal.
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  • Measured 24-hour urine creatinine clearance < 50 ml/min.
  • Active infection of any kind.
  • Unwilling or unable to follow protocol requirements or to give informed consent.
  • Dyspnea at rest or with minimal exertion.
  • No treatment with cytotoxic or biologic agents within the 4 weeks prior to beginning treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 4 weeks must have elapsed from any prior surgery, radiation, hormonal or other drug therapy for their cancer. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible.
  • Any of the following within 6 months prior to first dose of treatment: myocardial infarction, symptomatic coronary artery disease (severe or unstable angina), artery bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolus.
  • Known HIV infection. Patients with HIV infection are excluded because there may be unknown or dangerous drug interactions between sirolimus/SU11248 (Sutent®) and the anti-retroviral agents used to treat HIV infections.
  • Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication.
  • Diagnosis of second malignancy (except malignancies treated with no evidence of recurrence for at least 5 years, and curatively treated basal cell or squamous cell carcinomas of the skin, or in situ cervical cancer, or any stage I malignancy > 2 years from treatment).
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Patients taking concurrent medications of any kind which are strong inducers or inhibitors of CYP3A4. Patients receiving any of the following will be excluded: ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Yale Comprehensive Cancer Center at Yale University School of Medicine

    New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: A Phase I Trial of the Combination of Sirolimus and SU11248 (Sutent(R)) in Patients With Advanced Solid Tumors That Are Non-Curable With Standard Therapy

There are two drugs involved in this study. Sunitinib (Sutent(R)) is approved by the Food and Drug Administration (FDA) for the treatment of advanced renal cell (kidney) cancer and gastrointestinal stromal tumors. Sunitinib is thought to work by blocking the growth of blood vessels into tumors; reducing the blood supply to tumors can slow their growth and sometimes causes the tumors to shrink. Sirolimus has been approved by the FDA to prevent the body from rejecting organ transplants. Sirolimus is being tested for its effects against cancer because it can slow the growth of some tumors in animal models. Sirolimus is thought to slow cancer growth in these animal models both by direct effects on the tumor cells, and also by blocking production of growth factors that stimulate production of blood vessels. We hope that the combined use of these two drugs will have better anti-cancer effects than either agent alone. This study is designed to find out if different doses of Sirolimus combined with a standard dose of Sutent are safe and well tolerated. Additionally, it is hoped to gain knowledge about the way that Sutent(R) in combination with sirolimus affects the blood vessels produced by cancer.

Conditions
Tumors
Being tested
Sunitinib malate, Rapamycin
Keywords
metastatic, malignancy, advanced solid tumors, unresectable, Solid Tumors
Medical subject headings
Neoplasms, Neoplasm Metastasis

What participants receive

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

  • Sunitinib malateDrug

    Also called SU11248, SUTENT®

    C1: 50 mg po days 1-15, 2 weeks off C2: 50 mg po x 4 weeks, 2 weeks off

  • RapamycinDrug

    Also called Sirolimus, Rapamune

    Dose escalation until MTD as follows:

    C1: not given C2: 4 mg weekly, 8 mg weekly, 12 mg weekly, 20 mg weekly

Study groups in NCT00402415
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: Sunitinib malate; Drug: Rapamycin

What is being measured

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

  1. To determine the maximum tolerated dose of sirolimus when combined with a standard dose and schedule of Sutent(R)

    Measured: upon completion of dose escalation

Secondary outcomes (3)

  1. To obtain preliminary experience with dynamic MR imaging of tumor blood flow using the combination of Sutent(R) and sirolimus

    Measured: upon completion of study

  2. To provide preliminary data on dose effects of the combination on serum levels of VEGF and circulating endothelial cells

    Measured: upon completion of study

  3. To obtain preliminary information on the efficacy of Sutent(R)in combination with sirolimus in treating malignancies using RECIST criteria

    Measured: upon completion of study

Timeline

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

  1. First posted22 Nov 2006 (estimated)
  2. Study startFeb 2006
  3. Primary completionJul 2008
  4. Study completionJul 2008

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00402415
Sponsor's protocol ID
0510000723
Status last verified
Dec 2013
First submitted
20 Nov 2006
Last updated
18 Dec 2013
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sunitinib malate and Rapamycin in people with Tumors, run by Yale University 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 10 inclusion and 17 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: stopped early, as of the sponsor's last update on 18 Dec 2013. 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 was stopped early. Results are not available in the source record.

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?

To determine the maximum tolerated dose of sirolimus when combined with a standard dose and schedule of Sutent(R) (time frame: upon completion of dose escalation). 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 NCT00402415.

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 18 Dec 2013.

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