Locally Metastatic Malignant NeoplasmPhase 2NCT01616186
Everolimus/Sorafenib or Sunitinib in Patients With Metastatic Renal Cell Carcinoma (RCC)
A Phase 2 study testing Everolimus and sorafenib and Sunitinib monotherapy in people with Locally Metastatic Malignant Neoplasm, run by Andrea Harzstark.
Trial summary
This is a phase II trial that follows the completion of the phase I UCSF trial of everolimus and sorafenib for Renal Cell Carcinoma (RCC). This trial will be for patients who have not had treatment for RCC before. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Locally Metastatic Malignant Neoplasm
- What is being tested?
- Everolimus and sorafenib and Sunitinib monotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2012to Apr 2016
- Phase
- Phase 2
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically- or cytologically-confirmed renal cell carcinoma, which is unresectable or metastatic and of any of the following histologies: clear cell, papillary, chromophobic, oncocytic, unclassified, or mixed. A component of clear cell histology must be present. Tumors with pure collecting duct histology are not eligible.
- Cytoreductive nephrectomy is allowed but not required
- Evidence of RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥ 10 mm with spiral CT scan)
- Male or female at least 18 years old
- Female patients must be either surgically sterile or postmenopausal, or if of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment and agree to use effective barrier contraception during the period of therapy, and for 3 months after the end of treatment/end of participation in the study. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
- Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy, and for 3 months after the end of treatment/end of participation in the study.
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- The definition of effective contraception will be based on the judgment of the investigator.
- ECOG performance status 0-1
- Adequate bone marrow function:
- ANC ≥ 1500/uL
- platelet count ≥ 100,000/uL
- hemoglobin ≥ 9.0 g/dL
- Adequate hepatic function:
- Total bilirubin ≤ 1.5 X ULN
- AST (SGOT) ≤ 2.5 X ULN
- ALT (SGPT) ≤ 2.5 X ULN
- Adequate renal function as determined by either:
- Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated creatinine clearance, Cockroft-Gault equation will be used)
- Modified Cockcroft-Gault formula:
- ((140 - age (yrs)) x (actual weight(kg))) / (72 x serum creatinine(mg/dl))
- Multiply by another factor of 0.85 if female
- Serum creatinine ≤ 1.5 X ULN
- Able to swallow oral medications
- Total fasting serum cholesterol ≤ 300 mg/dL
- Resolution of any pre-existing toxicity from prior therapy to NCI CTCAE V3.0 ≤ grade 1 (with the exception of hypertension, hypothyroidism)
- Signed and dated informed consent document
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- More than 28 days since any prior therapy, including investigational agents and surgical procedures.
Who cannot join
- Collecting duct renal cell carcinoma is excluded. Transitional cell carcinoma of the renal pelvis is excluded.
- Prior systemic regimens for renal cell carcinoma (neoadjuvant therapy is acceptable as long as it did not include sunitinib, sorafenib, everolimus, or temsirolimus). A prior therapy which was started and stopped after no more than four weeks of therapy will not constitute a prior systemic regimen.
- Prior surgery, radiation therapy, or systemic therapy for renal cell carcinoma within 4 weeks of starting study treatment.
- History of or known brain metastasis, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan (evaluation for CNS disease is required to be performed for eligibility).
- Any of the following within 6 months prior to study drug administration: myocardial infarction, unstable or severe angina, coronary or peripheral artery bypass graft, NYHA functional Class II, III, IV congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
- Ejection fraction lower than institutional lower limit of normal by echocardiogram or MUGA.
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- Hypertension that is unable to be controlled with medications to a blood pressure of ≤ 150/90.
- Hypothyroidism that is unable to be controlled with medications such that FT4 is outside of normal limits.
- QTc prolongation (QTc interval ≥ 480 msecs) or any other clinically significant ECG abnormalities.
- Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness (because of the immunosuppressive effects of therapy). Testing for HIV in the absence of a history or symptoms is not required.
- Hepatitis B or C (because of the risk of reactivation). The following serologies are acceptable for enrollment: HBsAg-/anti-HBc-/anti-HBs-; HBsAg-/anti-HBc+/anti-HBs+; HBsAg-/anti-HBc-/anti-HBs+. The following serologies are not acceptable for enrollment: HBsAg+/anti-HBc+(IgM+/-)/anti-HBs-. If the following serologies are obtained, additional testing will be required to ascertain the patient's hepatitis B status: HBsAg-/anti-HBc+/anti-HBs-.
- "Currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered to have a less than 30% risk of relapse.
- Current treatment on another clinical trial.
- Pregnant or breastfeeding.
- Chronic treatment with systemic steroids or other immunosuppressive agent.
- On oral vitamin K antagonist medication (except low dose warfarin) (other anticoagulants are allowed).
- History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of stomach or small bowel that could interfere with absorption, distribution, metabolism, or excretion of study drugs.
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or obtaining informed consent. Examples of such include uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN (Note: optimal glycemic control should be achieved before starting trial therapy), nonhealing wound, severe infection, severe malnutrition, ventricular arrhythmias, active ischemic heart disease, chronic liver or renal disease, or active upper GI tract ulceration.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
About this study
Official title: A Randomized Non-Comparative Multicenter Phase II Study of Everolimus/Sorafenib or Sunitinib in Patients With Metastatic Renal Cell Carcinoma (RCC)
This is a phase II trial that follows the completion of the phase I UCSF trial of everolimus and sorafenib for Renal Cell Carcinoma (RCC). This trial will be for patients who have not had treatment for RCC before. This trial will have 2/3 patients getting everolimus/sorafenib treatment and 1/3 getting sunitinib, an FDA approved RCC drug. All three drugs are approved for advanced RCC when used individually, the combination of everolimus and sorafenib for RCC is not approved by the FDA.
Read the detailed description
In the phase I study of the combination of everolimus and sorafenib, clinical benefit was observed in patients with no prior systemic therapy. There was no evidence of pharmacokinetic interaction and acceptable toxicity at a dosage of sorafenib of 400 mg twice daily (BID) and everolimus 5 mg daily. Based on these data and the need for more effective front-line therapy for renal cell carcinoma, the plan is to investigate this regimen in patients who have not undergone prior therapy. A sunitinib arm is being included as a concurrent reference to help provide a guideline of an activity level and toxicity that would be meaningful to move forward to a phase III study. Therefore, this study is designed as a non-comparative investigation and patients will be randomized in a 2:1 ratio to everolimus/sorafenib or to sunitinib, respectively.
- Conditions
- Locally Metastatic Malignant Neoplasm
- Being tested
- Everolimus and sorafenib, Sunitinib monotherapy
- Keywords
- Renal Cell Carcinoma
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus and sorafenibDrug
- Starting doses: everolimus 5 mg daily and sorafenib 400 mg BID - taken fasting, no food 1 hour before or 2 hours after dosing
- Everolimus and sorafenib are dosed continuously (Note: everolimus and sorafenib are typically dosed in 28 day cycles, and sunitinib is typically dosed in 42 day cycles; for the purposes of this protocol to keep timing consistent, a cycle will be defined as 42 days of therapy)
Sunitinib monotherapyDrug
Starting dose: sunitinib 50 mg daily 4 weeks on, 2 weeks off - taken fasting, no food 1 hour before or 2 hours after dosing
(Note: sunitinib is typically dosed in 42 day cycles described above: 28 days treatment, 14 days off. For the purposes of this protocol, to keep timing consistent, a cycle will be defined as 42 days of therapy)
| Study group | Role | What they receive |
|---|---|---|
| Everolimus/Sorafenib | Experimental | Patients will be stratified by current smoking status (smoker: yes or no0, for each smoking stratum patients will be randomized in a 2:1 ratio Receives: Drug: Everolimus and sorafenib |
| Sunitinib | Active comparator | * Sunitinib is the concurrent control group
* Patients will be stratified by current smoking status (smoker: yes or no), for each smoking stratum patients will be randomized in a 2:1 ratio Receives: Drug: Sunitinib monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response
Computerized Tomography Scans (CT) done at Screening and every 2 cycles
- For Partial Response (PR) or Complete Response (CR), changes in tumor measurements must be confirmed by repeat studies no less than 4 weeks after the criteria for response are first met (RECIST 1.1 criteria)
- For Stable Disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum of 12 weeks after study entry
Measured: 12-18 weeks
Secondary outcomes (4)
Safety: combination of everolimus and sorafenib
Safety/Adverse Event (AE) assessments done on Day 1, 21, 42 during Cycle 1 \& Day 28 of all subsuquent cycles; assessments include Eastern Oncology Group Conference (ECOG) Performance scale, physical/history, hematology \& chemistry labs; other safety data (e.g. Electrocardiogram [ECG], Multigated Acquisition Scan [MUGA], etc.) will be considered as appropriate
Measured: 12-18 weeks
Progression-free Survival (PFS)
- PFS will be measured (using RECIST 1.1 criteria) from the start of protocol therapy until the date of the first occurrence of recurrent or progressive disease or death
Measured: 12-18 weeks
Time-to-Progression (TTP)
- TTP will be measured from the start of protocol therapy until first date that recurrent or progressive disease is documented
Measured: 12-18 weeks
Clinical Benefit rate
Clinical benefit (defined as objective response+stable disease) will be summarized for each treatment arm by the proportion of patients achieving this outcome with 95% confidence intervals
Measured: 12-18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionDec 2015 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Metastatic Malignant NeoplasmStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrea Harzstark
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, Andrea Harzstark, University of California, San Francisco
- Investigators
- Andrea Harzstark, MD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01616186
- Sponsor's protocol ID
- UCSF CC# 12521
- Status last verified
- Apr 2013
- First submitted
- 4 Jun 2012
- Last updated
- 8 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Non-Comparative Multicenter Phase II Study of Everolimus/Sorafenib or Sunitinib in Patients With Metastatic Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT01616186
- Acronym / sponsor ID
- UCSF CC# 12521
- Conditions
- Locally Metastatic Malignant Neoplasm
- Keywords
- Renal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Andrea HarzstarkUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jul 2012
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 11 Jun 2012 (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.
This is a phase II trial that follows the completion of the phase I UCSF trial of everolimus and sorafenib for Renal Cell Carcinoma (RCC). This trial will be for patients who have not had treatment for RCC before. This trial will have 2/3 patients getting everolimus/sorafenib treatment and 1/3 getting sunitinib, an FDA approved RCC drug. All three drugs are approved for advanced RCC when used individually, the combination of everolimus and sorafenib for RCC is not approved by the FDA.
Detailed description
In the phase I study of the combination of everolimus and sorafenib, clinical benefit was observed in patients with no prior systemic therapy. There was no evidence of pharmacokinetic interaction and acceptable toxicity at a dosage of sorafenib of 400 mg twice daily (BID) and everolimus 5 mg daily. Based on these data and the need for more effective front-line therapy for renal cell carcinoma, the plan is to investigate this regimen in patients who have not undergone prior therapy. A sunitinib arm is being included as a concurrent reference to help provide a guideline of an activity level and toxicity that would be meaningful to move forward to a phase III study. Therefore, this study is designed as a non-comparative investigation and patients will be randomized in a 2:1 ratio to everolimus/sorafenib or to sunitinib, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus/Sorafenib | Experimental | Drug: Everolimus and sorafenibPatients will be stratified by current smoking status (smoker: yes or no0, for each smoking stratum patients will be randomized in a 2:1 ratio |
| Sunitinib | Active comparator | Drug: Sunitinib monotherapy* Sunitinib is the concurrent control group * Patients will be stratified by current smoking status (smoker: yes or no), for each smoking stratum patients will be randomized in a 2:1 ratio |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Histologically- or cytologically-confirmed renal cell carcinoma, which is unresectable or metastatic and of any of the following histologies: clear cell, papillary, chromophobic, oncocytic, unclassified, or mixed. A component of clear cell histology must be present. Tumors with pure collecting duct histology are not eligible.
- Cytoreductive nephrectomy is allowed but not required
- Evidence of RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥ 10 mm with spiral CT scan)
- Male or female at least 18 years old
- ECOG performance status 0-1
Key exclusion criteria (19 listed)
- Collecting duct renal cell carcinoma is excluded. Transitional cell carcinoma of the renal pelvis is excluded.
- Prior systemic regimens for renal cell carcinoma (neoadjuvant therapy is acceptable as long as it did not include sunitinib, sorafenib, everolimus, or temsirolimus). A prior therapy which was started and stopped after no more than four weeks of therapy will not constitute a prior systemic regimen.
- Prior surgery, radiation therapy, or systemic therapy for renal cell carcinoma within 4 weeks of starting study treatment.
- History of or known brain metastasis, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan (evaluation for CNS disease is required to be performed for eligibility).
- Any of the following within 6 months prior to study drug administration: myocardial infarction, unstable or severe angina, coronary or peripheral artery bypass graft, NYHA functional Class II, III, IV congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
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 |
|---|---|---|
| Everolimus and sorafenib* Starting doses: everolimus 5 mg daily and sorafenib 400 mg BID - taken fasting, no food 1 hour before or 2 hours after dosing * Everolimus and sorafenib are dosed continuously (Note: everolimus and sorafenib are typically dosed in 28 day cycles, and sunitinib is typically dosed in 42 day cycles; for the purposes of this protocol to keep timing consistent, a cycle will be defined as 42 days of therapy) | Drug | Everolimus/Sorafenib |
| Sunitinib monotherapyStarting dose: sunitinib 50 mg daily 4 weeks on, 2 weeks off - taken fasting, no food 1 hour before or 2 hours after dosing (Note: sunitinib is typically dosed in 42 day cycles described above: 28 days treatment, 14 days off. For the purposes of this protocol, to keep timing consistent, a cycle will be defined as 42 days of therapy) | Drug | Sunitinib |
Primary outcome
Objective response
Time frame: 12-18 weeks
Computerized Tomography Scans (CT) done at Screening and every 2 cycles * For Partial Response (PR) or Complete Response (CR), changes in tumor measurements must be confirmed by repeat studies no less than 4 weeks after the criteria for response are first met (RECIST 1.1 criteria) * For Stable Disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum of 12 weeks after study entry
4 secondary outcomes
Safety: combination of everolimus and sorafenib
Time frame: 12-18 weeks
Progression-free Survival (PFS)
Time frame: 12-18 weeks
Time-to-Progression (TTP)
Time frame: 12-18 weeks
Clinical Benefit rate
Time frame: 12-18 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2013.
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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.
Andrea Harzstark, MD study chair
University of California, San Francisco
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and sorafenib and Sunitinib monotherapy in people with Locally Metastatic Malignant Neoplasm, run by Andrea Harzstark.
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 28 inclusion and 19 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: withdrawn, as of the sponsor's last update on 8 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Objective response (time frame: 12-18 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2013.