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

NCT00402415

Last updated date
Study Location
Yale Comprehensive Cancer Center at Yale University School of Medicine
New Haven, Connecticut, 06520, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Tumors
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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.

- 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

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.


- 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.

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TumorsStudy of Combination of Sirolimus and Sutent in Patients With Advanced Solid Tumors Non-Curable With Standard Therapy
NCT00402415
  1. New Haven, Connecticut
ALL GENDERS
18 Years+
years
MULTIPLE SITES
TumorsStudy Evaluating SKI-606 in Subject With Solid Tumors
NCT01001936
ALL GENDERS
20 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Study of Combination of Sirolimus and Sutent in Patients With Advanced Solid Tumors Non-Curable With Standard Therapy
Official Title  ICMJE 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
Brief 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. 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Tumors
Intervention  ICMJE
  • Drug: Sunitinib malate
    C1: 50 mg po days 1-15, 2 weeks off C2: 50 mg po x 4 weeks, 2 weeks off
    Other Names:
    • SU11248
    • SUTENT®
  • Drug: Rapamycin

    Dose escalation until MTD as follows:

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

    Other Names:
    • Sirolimus
    • Rapamune
Study Arms  ICMJE Experimental: 1
Interventions:
  • Drug: Sunitinib malate
  • Drug: Rapamycin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 17, 2013)
18
Original Enrollment  ICMJE
 (submitted: November 21, 2006)
30
Actual Study Completion Date  ICMJE July 2008
Actual Primary Completion Date July 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • 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

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00402415
Other Study ID Numbers  ICMJE 0510000723
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Mario Sznol, M.D.Yale University
PRS Account Yale University
Verification Date December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP