Everolimus Versus Sunitinib in Non-Clear Cell Renal Cell Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01185366
First received: August 18, 2010
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

The goal of this clinical research study is to compare the effectiveness of Afinitor (everolimus) and Sutent (sunitinib) for the treatment of advanced renal cell carcinoma (kidney cancer). The safety of each treatment will also be studied.


Condition Intervention Phase
Kidney Cancer
Drug: Everolimus
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Everolimus Versus Sunitinib Therapy in Patients With Advanced Non-clear Cell Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Beginning of every 6 week cycle from baseline to disease progression or intolerable side effects. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 108
Study Start Date: August 2010
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus Group 1
Everolimus 10 mg by mouth once a day.
Drug: Everolimus
10 mg by mouth once a day.
Other Names:
  • Afinitor
  • RAD001
Active Comparator: Sunitinib Group 2
Sunitinib 50 mg by mouth daily for 4 weeks on / 2 weeks off.
Drug: Sunitinib
50 mg by mouth daily for 4 weeks on / 2 weeks off
Other Names:
  • Sunitinib Malate
  • SUO11248
  • Sutent

  Hide Detailed Description

Detailed Description:

The Study Drugs:

Everolimus is designed to stop cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, which may cause the tumor cells to die.

Sunitinib is designed to block pathways that control important events (such as the growth of blood vessels) that are essential for the growth of cancer.

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups.

  • If you are assigned to Group 1, you will take 2 everolimus tablets by mouth once every day.
  • If you are assigned to Group 2, you will take sunitinib capsules by mouth every day for 4 weeks, followed by 2 weeks off.

If you have any side effects from any of the drugs, tell the study doctor right away. The study doctor may then lower the dose or keep the dose level the same.

Every 6 weeks on this study is called a study "cycle."

If the disease gets worse or you have intolerable side effects while you are on study, you will have the chance to receive the study drug that you did not receive at first. The dosing and follow-up will be the same as for all participants in that group.

Study Visits:

On Day 1 of every cycle:

  • You will have a physical exam, including measurement of your vital signs.
  • You will be asked about any drugs or treatments you may be receiving.
  • Your performance status will be recorded.
  • Blood (about 3 teaspoons) and urine will be collected for routine tests and a fasting blood sugar test. Blood or urine will also be used for a pregnancy test for women who are able to have children. If you are in Group 1, you will have an additional 1 teaspoon of blood drawn to test your cholesterol.

On Day 15 and 29 of Cycle 1:

  • Your vital signs and weight will be measured.
  • Blood (about 2 teaspoons) will be drawn for routine tests. If you are in Group 1, an additional 1 teaspoon of blood will be drawn to measure your cholesterol.

The Day 15 and Day 29 tests may be done at your local doctor's office.

On Day 1 of Cycles 2 and 3, and every other cycle after that (Day 1 of Cycle 5, 7, 9 and so on):

-You will have a CT scan of the chest and a CT scan or MRI of the abdomen to check the status of the disease.

Every 4 cycles (24 weeks):

-If you are in Group 2, you will have an echocardiogram or MUGA scan to check your heart's health.

Length of Study:

You may continue taking the study drugs for as long as you are benefiting. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Treatment Visit:

If you have stopped taking the study drug because of intolerable side effects, the treating physician will make every effort to check the status of the disease before you are taken off of study.

Long-Term Follow-up:

Once you are no longer on this study, the research staff will check up on you about every 6 months. This update will consist of a phone call or a review of your medical and/or other records. You will not have any extra tests, procedures, or study visits. If contacted by phone, the call would only last about 5 minutes.

This is an investigational study. Sunitinib and everolimus are both FDA approved and commercially available for the treatment of advanced kidney cancer.

Up to 108 patients will be enrolled in this multicenter trial. Up to 108 patients will be enrolled at MD Anderson.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have advanced non-clear cell RCC, which may include but is not limited to the following subtypes: papillary I or II, chromophobe, collecting duct carcinoma (CDC), translocation or unclassified. Patients with conventional-type renal cell carcinoma who have >/= 20% sarcomatoid component in their primary tumor are eligible. Patients who have sarcomatoid features in FNA or core biopsy of any metastatic site are eligible, if they have an underlying renal cell carcinoma primary tumor.
  2. Patients must have at least one measurable site of disease that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
  3. ECOG performance status 0-1
  4. Age >/= 18 years
  5. Patients must have adequate organ and marrow function within 14 days prior to study entry as defined below: a) Hemoglobin >/= 9 g/dl (tx allowed); b) absolute neutrophil count >/=1,500/microL; c) platelets >/= 100,000/microL; d) total bilirubin </= 1.5 mg/dl; e) AST(SGOT) or ALT (SGPT) </=2.5 X institutional uln, except in known hepatic metastasis, wherein may be </= 5 x ULN; f) Serum Creatinine </= 1.5 x ULN (as long as patient does not require dialysis)
  6. INR and PTT </= 1.5 x ULN within 14 days prior to study entry. Therapeutic anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of randomization.
  7. Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN within 14 days prior to study entry.
  8. Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days before study entry. Pregnancy test must be repeated if performed > 14 days before starting study drug.
  9. Patients must give written informed consent prior to study entry, in keeping with the policies of each institution.
  10. Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy.
  11. Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or Gamma knife, without recurrence or edema for 3 months (90days).

Exclusion Criteria:

  1. No other malignancies within the past 2 years except for adequately treated carcinoma of the cervix or basal (without recurrence post-surgery or post-radiotherapy) or squamous cell carcinomas of the skin.
  2. No prior systemic therapy for RCC including prior adjuvant therapy or investigational drug is allowed.
  3. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks (28 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. However, patients are permitted to receive bisphosphonates. Also, patients who completed palliative radiation therapy prior to enrollment in this trial are eligible.
  4. Patients, who have had a major surgery or significant traumatic injury (injury requiring > 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
  5. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital) or CYP3A4 inhibitors is not recommended on this study.
  6. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic congestive heart failure of New York heart Association Class III or IV; b) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c) severely impaired lung function as defined as 02 saturation that is 88% or less at rest on room air
  7. (#6 cont'd) d) uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN; e) active (acute or chronic) or uncontrolled severe infections requiring antibiotic intervention; f) liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  8. Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of sunitinib or everolimus or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  9. Concomitant treatment with drugs with dysrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and indapamide) is not recommended.
  10. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  11. Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period.
  12. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  13. A known history of HIV sero-positivity.
  14. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus and/or sunitinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  15. Patients with an active, bleeding diathesis.
  16. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to study entry. Pregnancy test must be repeated if performed > 7 days before administration of everolimus and sunitinib)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185366

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Nizar M. Tannir, MD, FACP UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01185366     History of Changes
Other Study ID Numbers: 2009-0628, NCI-2012-01789
Study First Received: August 18, 2010
Last Updated: April 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced non-clear cell renal cell cancer (RCC)
Clear-cell renal cell carcinoma
Collecting duct carcinoma
Translocation carcinoma
Chromophobe
Everolimus
Sunitinib
Afinitor
RAD001
Sunitinib Malate
SUO11248
Sutent
ESPN

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Everolimus
Sirolimus
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014