Renal Cell CarcinomaPhase 2NCT00557830
Randomized Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma
A Phase 2 study testing Sorafenib Escalated Dose and Sorafenib Standard Dose in people with Renal Cell Carcinoma, run by Accelerated Community Oncology Research Network at 13 sites in United States.
Trial summary
The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Sorafenib Escalated Dose and Sorafenib Standard Dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 13 sitesUnited States
- Study dates
- Jan 2008to Apr 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age ≥18 years old.
- Diagnosis of unresectable/metastatic renal cell carcinoma (RCC). Nonclear cell histology is permitted (except for medullary, collecting duct, or sarcomatoid >50% of specimen). Prior metastasectomy is permitted as long as there is measurable disease at time of consent.
- Karnofsky Performance Status of 50% or greater at study entry.
- Adequate bone marrow, liver and renal function as assessed by the following: o Hemoglobin ≥ 9.0 g/dL. o ANC ≥ 1500/mm3. o Platelet count ≥ 100,000/mm3. o Total bilirubin ≤ 1.5 ULN. o ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver involvement). o Creatinine ≤ 1.5 × ULN.
- Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.
- Women of childbearing potential and sexually active men must agree to use adequate barrier contraception prior to study entry, for the duration of study participation, and for at least three months after the last administration of sorafenib.
- INR < 1.5 or a PT/ PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
Who cannot join
- Prior systemic anticancer treatment for metastatic disease, including investigational therapy.
- Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting.
- Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease.
- Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment.
- Hemodialysis or peritoneal dialysis.
- Treatment with radiotherapy within 2 weeks of enrollment.
Show all 21Show fewer
- Cardiac disease: Congestive heart failure Class II or higher per NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Uncontrolled CNS metastases. All patients must undergo a CT) scan/MRI of the brain to exclude brain metastasis. Patients with adequately treated CNS disease may be considered for participation as long as the first dose of sorafenib is 4 weeks after completion of CNS therapy.
- Uncontrolled hypertension defined as SBP > 150 mmHg or DBP > 90 mmHg, despite optimal medical management.
- Active clinically serious infection > Grade 2 per the CTCAE v3.
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
- Any other hemorrhage/bleeding event ≥ Grade 3 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
- Serious non-healing wound, ulcer, or bone fracture.
- Evidence or history of bleeding diathesis or coagulopathy.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of administration of the first study drug dose.
- Use of St. John's Wort, rifampin (rifampicin), phenytoin, Phenobarbital, carbamazepine, dexamethasone.
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem.
- Pregnancy or lactation.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Northeast Georgia Cancer Care
Athens, Georgia, 30607
Peachtree Hematology Oncology Consultants
Atlanta, Georgia, 30309
Pacific Oncology, PC
Beaverton, Oregon, 97006
Hematology Oncology Centers of the Northern Rockies
Billings, Montana, 59101
Gaston Hematology and Oncology
Gastonia, North Carolina, 28054
Clopton Clinic
Jonesboro, Arkansas, 72401
Wilshire Oncology Medical Group, Inc.
La Verne, California, 91750
The Lancaster Cancer Center, Ltd
Lancaster, Pennsylvania, 17605
Central Georgia Cancer Care
Macon, Georgia, 31201
Northwest Georgia Oncology Centers
Marietta, Georgia, 30060
The West Clinic
Memphis, Tennessee, 38120
Advanced Medical Specialties
Miami, Florida, 33176
Mid-Illinois Hematology and Oncology Associates, Ltd.
Normal, Illinois, 61761
About this study
Official title: Randomized Phase IIb Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (RCC)
The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC.
The secondary objectives are to evaluate the effects of the dose-escalation regimen on the quality of life (QoL) of patients with metastatic RCC and to characterize the safety and tolerability profile of a dose-escalation regimen of sorafenib in patients with metastatic RCC.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Sorafenib Escalated Dose, Sorafenib Standard Dose
- Keywords
- Renal Cell Carcinoma, Kidney Cancer
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib Escalated DoseDrug
Also called Nexavar
Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
Sorafenib Standard DoseDrug
Also called Nexavar
Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Escalated Dose | Active comparator | Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Receives: Drug: Sorafenib Escalated Dose |
| Group B: Standard Dose | Active comparator | Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Receives: Drug: Sorafenib Standard Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.
Measured: Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.
Secondary outcomes (3)
PFS Rate at 9, 13 and 17 Months
Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.
Measured: PFS was to be measured at 9, 13, and 17 months.
Overall Survival Rate
Due to the early study closure and the small sample size, overall survival rate was not evaluated.
Measured: Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.
Changes From Baseline in Symptom Burden
The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment.
The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible).
Measured: The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2007 (estimated)
- Study startJan 2008
- Primary completionApr 2011
- Study completionApr 2011
Why it stopped: The study was closed to enrollment when it became clear that enrollment was too slow to complete the full enrollment target within the time frame allowed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Cell CarcinomaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Accelerated Community Oncology Research Network
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Vasily Assikis, MD, Principal investigator, Acorn Cardiovascular, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00557830
- Sponsor's protocol ID
- AVJARCC0702
- Status last verified
- Jul 2013
- First submitted
- 9 Nov 2007
- Last updated
- 18 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase IIb Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT00557830
- Acronym / sponsor ID
- AVJARCC0702
- Conditions
- Renal Cell Carcinoma
- Keywords
- Renal Cell Carcinoma, Kidney Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was closed to enrollment when it became clear that enrollment was too slow to complete the full enrollment target within the time frame allowed.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Accelerated Community Oncology Research NetworkUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jan 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 14 Nov 2007 (estimated)
- Results
- Posted 18 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC.
The secondary objectives are to evaluate the effects of the dose-escalation regimen on the quality of life (QoL) of patients with metastatic RCC and to characterize the safety and tolerability profile of a dose-escalation regimen of sorafenib in patients with metastatic RCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Escalated Dose | Active comparator | Drug: Sorafenib Escalated DoseEligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. |
| Group B: Standard Dose | Active comparator | Drug: Sorafenib Standard DoseEligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥18 years old.
- Diagnosis of unresectable/metastatic renal cell carcinoma (RCC). Nonclear cell histology is permitted (except for medullary, collecting duct, or sarcomatoid >50% of specimen). Prior metastasectomy is permitted as long as there is measurable disease at time of consent.
- Karnofsky Performance Status of 50% or greater at study entry.
- Adequate bone marrow, liver and renal function as assessed by the following: o Hemoglobin ≥ 9.0 g/dL. o ANC ≥ 1500/mm3. o Platelet count ≥ 100,000/mm3. o Total bilirubin ≤ 1.5 ULN. o ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver involvement). o Creatinine ≤ 1.5 × ULN.
- Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.
Key exclusion criteria (21 listed)
- Prior systemic anticancer treatment for metastatic disease, including investigational therapy.
- Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting.
- Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease.
- Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment.
- Hemodialysis or peritoneal dialysis.
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 |
|---|---|---|
| Sorafenib Escalated DoseAlso: NexavarPatients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. | Drug | Group A: Escalated Dose |
| Sorafenib Standard DoseAlso: NexavarPatients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. | Drug | Group B: Standard Dose |
Primary outcome
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Time frame: Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.
Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.
3 secondary outcomes
PFS Rate at 9, 13 and 17 Months
Time frame: PFS was to be measured at 9, 13, and 17 months.
Overall Survival Rate
Time frame: Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.
Changes From Baseline in Symptom Burden
Time frame: The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Vasily Assikis, MD principal investigator
Acorn Cardiovascular, Inc.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib Escalated Dose and Sorafenib Standard Dose in people with Renal Cell Carcinoma, run by Accelerated Community Oncology Research Network at 13 sites 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 8 inclusion and 21 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 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites 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 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?
Yes. Results are posted in the registry (first posted 18 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. (time frame: Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.). 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 18 Jul 2013.