SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma
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| ClinicalTrials.gov Identifier: NCT00083889 |
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Recruitment Status :
Completed
First Posted : June 4, 2004
Results First Posted : December 10, 2009
Last Update Posted : January 26, 2010
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Sponsor:
Pfizer
Information provided by:
Pfizer
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Brief Summary:
The purpose of this study is to test whether SU011248 has activity and is safe compared to interferon-alfa as first-line therapy in patients with metastatic renal cell carcinoma (RCC).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Renal Cell | Drug: Interferon-alfa Drug: SU011248 | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 750 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized Study Of SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma |
| Study Start Date : | August 2004 |
| Actual Primary Completion Date : | September 2008 |
| Actual Study Completion Date : | September 2008 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: 2 |
Drug: Interferon-alfa
3 MIU first week, 6 MIU second week, and 9 MIU thereafter three times a week (non-consecutive days) until progression or unacceptable toxicity
Other Name: Roferon |
| Experimental: 1 |
Drug: SU011248
50 mg orally daily for 4 weeks and 2 weeks off treatment until progression or unacceptable toxicity
Other Name: Sunitinib, SUTENT |
Primary Outcome Measures :
- Progression-Free Survival (PFS), Core Radiology Assessment [ Time Frame: Day 28 of each 6-week cycle: duration of treatment phase ]Progression-free survival (PFS) = time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. PFS = first event date minus the date of randomization + 1. On study included treatment plus 28-day follow-up periods.
- Progression-Free Survival (PFS), Investigator's Assessment [ Time Frame: Day 28 of each 6-week cycle: duration of treatment phase ]Progression-free survival = time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occured first. PFS = first event date minus the date of randomization + 1). On study included treatment plus 28-day follow-up periods.
Secondary Outcome Measures :
- Objective Response, Core Radiology Assessment [ Time Frame: Day 28 of each 6-week cycle: duration of treatment phase ]Objective response (OR) = the number of patients with confirmed complete response (CR) and confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, relative to all randomized patients. CR was defined as the disappearance of all target lesions. PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR or PR) = those that persisted on repeat imaging study >= 4 weeks after initial documentation of response.
- Objective Response, Investigator's Assessment [ Time Frame: Day 28 of each 6-week cycle: duration of treatment phase ]Objective response (OR) = the number of patients with confirmed complete response (CR) and confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, relative to all randomized patients. CR was defined as the disappearance of all target lesions. PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses = those that persist on repeat imaging study >= 4 weeks after initial documentation of response.
- Overall Survival (OS) [ Time Frame: Clinic visit or telephone contact every 2 months until death ]Overall survival (OS) = time from date of randomization to date of death due to any cause. For patients not expiring, survival time was censored at the last date they were known to be alive. Patients lacking data beyond randomization had their survival times censored at the date of randomization with a duration of 1 day.
- Time to Tumor Progression (TTP), Core Radiology Assessment [ Time Frame: Randomization to first documentation of tumor progression: duration of treatment phase ]TTP = time from randomization to first documentation of objective tumor progression. TTP data were censored on the day following the date of last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects who did not have objective tumor progression while on treatment or who were given anti-tumor treatment other than study treatment prior to documentation of objective tumor progression. Subjects with no tumor assessments after randomization had TTP censored on the date of randomization with a duration of 1 day.
- Time to Tumor Progression (TTP), Investigator's Assessment [ Time Frame: Randomization to first documentation of tumor progression: duration of treatment phase ]TTP = time from randomization to first documentation of objective tumor progression. TTP data were censored on the day following the date of last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects who did not have objective tumor progression while on treatment or who were given anti-tumor treatment other than the study treatment prior to documentation of objective tumor progression. Subjects with no tumor assessments after randomization had TTP censored on the date of randomization with a duration of 1 day.
- Duration of Response (DR), Core Radiology Assessement [ Time Frame: Day 28 of each cycle: duraton of treatment phase ]Duration of response (DR) = time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause. DR data were censored on the day following the date of the last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects without objective tumor progression who did not die due to any cause while on treatment or who were given anti-tumor treatment other than study treatment prior to observing tumor progression.
- Duration of Response (DR), Investigator's Assessment [ Time Frame: Day 28 of each cycle: duration of treatment phase ]Duration of response (DR) = time from the first documentation of objective tumor response to the first documentaion of objective tumor progression or to death due to any cause. DR data were censored on the day following the date of the last on treatment (including 28 day follow-up period) tumor assessment documenting absence of progressive disease for subjects without objective tumor progression who did not die due to any cause while on treatment or who were given anti-tumor treatment other than study treatment prior to observing tumor progression.
- FACT-Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Subscale [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]FACT-Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) subscale of the FKSI to measure advanced kidney cancer disease related symptoms. Includes 9 items: lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria. Each question was answered on a five-point Likert-type scale ranging from 0 (not at all) to 4 (very much). Score = the sum score of the item scores in the subscale; total range: 0 to 36. A score greater than 0 indicates the difference favored sunitinib.
- FACT-Kidney Symptom Index (FKSI) Subscale [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]FACT-Kidney Symptom Index (FKSI) subscale designed to be a stand-alone instrument to measure symptoms and quality of life in patients with advanced kidney cancer. Contains 15 questions; some questions overlap with the FACT-G questions. Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Total FKSI score = sum score of the 15 item scores; total range: 0 - 60; 0 (most severe symptoms and concerns) to 60 (no symptoms or concerns).
- Functional Assessment of Cancer Therapy-General (FACT-G) [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]Functional Assessment of Cancer Therapy-General (FACT-G): core questionnaire of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system that has been validated in a variety of cancer populations. 27 questions grouped into 4 domains that measure a patient's physical, functional, social and family, and emotional well-being. Five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = sum score of item scores in the subscale; total range: 0 to 108 with higher score indicating better quality of life.
- Functional Assessment of Cancer Therapy-General (FACT-G): Physical Well Being (PWB) Subscale [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]Physical well-being (PWB) subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; lower score indicates better physical well-being.
- Functional Assessment of Cancer Therapy-General (FACT-G): Social/Family Well Being (SWB) Subscale [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]Social/family well-being (SWB)subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; lower score indicates less social/family well-being.
- Functional Assessment of Cancer Therapy-General (FACT-G): Emotional Well Being (EWB) Subscale [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]Emotional well-being (EWB)subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 24; lower score indicates better emotional well-being.
- Functional Assessment of Cancer Therapy-General (FACT-G): Functional Well Being (FWB) Subscale [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]Functional well-being (FWB) subscale of the Functional Assessment of Cancer Therapy-General (FACT-G). Each question was answered on a five-point Likert-type scale ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Score = the sum score of the item scores in the subscale; range: 0 to 28; higher score indicates greater functional well-being.
- EuroQoL Five Dimension (EQ-5D) Health State Index [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]EQ-5D Health State Index: a brief, self-administered generic health status instrument. Respondents were asked to describe their current health state on each of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety or depression) on a three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A maximum score of 1 can be derived from these 5 dimensions by score conversion; range: -0.39 (worst health state)to 1.00 (best health state). This descriptive system classifies respondents into one of 243 possible distinct health states (EQ-5D descriptive system).
- Euro-QoL Visual Analog Scale (EQ-VAS) [ Time Frame: Day 1 & 28 of each cycle: duration of treatment phase ]EQ-VAS: overall self-rating rating of the patient's current health state using a 20 cm Visual Analog Scale (EQ-VAS), also called the health state thermometer) is a metric measurement (in 2 mm interval) from the visual analog scale which ranges between 0 (worse imaginable health state) and 100 (best imaginable health state).
- Plasma Concentrations of Soluble Proteins: Plasma VEGF-A, Plasma VEGF-C, Plasma sVEGFR-3, PLASMA IL-8, and PLASMA bFGF That May be Associated With Tumor Proliferation or Angiogenesis [ Time Frame: Day 1 & Day 28, Cycle 1 to Cycle 4 ]Plasma concentrations of soluble proteins that may be associated with tumor proliferation or angiogenesis collected from a subset of patients were analyzed by enzyme-linked immunosorbent assay (ELISA) analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio = plasma concentration of soluble protein (picograms per milliliter [pg/ml]) at timepoint / concentration of soluble protein (pg/ml) at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
- Plasma Concentrations of Soluble Proteins: Plasma Basic Fibroblast Growth Factor (bFGF) That May be Associated With Tumor Proliferation or Angiogenesis [ Time Frame: Day 1 & Day 28, Cycle 1 to Cycle 4 ]Plasma concentrations of soluble proteins that may be associated with tumor proliferation or angiogenesis collected from a subset of patients were analyzed by enzyme-linked immunosorbent assay (ELISA) analysis. Soluble protein values: Baseline concentration (pM) and ratio to Baseline at each timepoint; ratio = plasma concentration of soluble protein (picograms per milliliter [pg/ml]) at timepoint / concentration of soluble protein (pg/ml) at baseline. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
- Incremental Cost Effectiveness Ratio (ICER) [ Time Frame: post study measurement ]Incremental cost effectiveness ratio (ICER) of sunitinib compared to IFN-a as first-line treatment for MRCC, defined as the ratio of the incremental cost of treatment over the incremental effectiveness; effectiveness measured as quality adjusted life year (QALY) gain. This objective was not addressed in the clinical study report, but an interim analysis of cost-effectiveness was presented separately. These results were not available for inclusion at the time of this posting.
- Ctrough Concentrations of SU011248 [ Time Frame: Day 28 of Cycle 1 to Cycle 4 ]Subject observed Ctrough (trough drug) concentrations of SU011248 per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter [ng/mL]).
- Ctrough Concentrations of Metabolite SU012662 [ Time Frame: Day 28 of Cycle 1 to Cycle 4 ]Subject observed Ctrough (trough drug) concentrations of active metabolite SU012662 per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter [ng/mL]).
- Ctrough Concentrations of SU011248 and Active Metabolite SU012662 [ Time Frame: Day 28 of Cycle 1 to Cycle 4 ]Subject observed Ctrough (trough drug) concentrations of total drug (SU011248 and its active metabolite SU012662) per cycle and study day determined by plasma trough samples collected from a subset of patients. Steady-state observed trough concentrations were dose corrected to the starting dose (reference dose) where appropriate. Concentrations below the limits of quantitation (BLQ) were set to 0. Ctrough = minimum (trough) plasma concentration (nanograms per milliliter [ng/mL]).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Histologically confirmed renal cell carcinoma of clear cell histology with metastases
- Evidence of measurable disease by radiographic technique
- Eastern Cooperative Oncology Group [ECOG] performance status of 0 or 1
Exclusion Criteria:
- Prior systemic (including adjuvant or neoadjuvant) therapy of any kind for RCC
- History of or known brain metastases
- Serious acute or chronic illness or recent history of significant cardiac abnormality
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00083889
Locations
Show 124 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Director, Clinical Trial Disclosure Group, Pfizer Inc |
| ClinicalTrials.gov Identifier: | NCT00083889 |
| Obsolete Identifiers: | NCT00098657 |
| Other Study ID Numbers: |
A6181034 |
| First Posted: | June 4, 2004 Key Record Dates |
| Results First Posted: | December 10, 2009 |
| Last Update Posted: | January 26, 2010 |
| Last Verified: | January 2010 |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Adenocarcinoma Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Kidney Diseases Urologic Diseases |
Male Urogenital Diseases Interferons Interferon-alpha Sunitinib Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors |