Metastatic Renal Cell Carcinoma
Conditions
Keywords
Kidney, Renal Cell, Metastatic, interleukin-2, select
Brief summary
High-dose interleukin 2 (Proleukin, Novartis) (IL-2) is approved by the U.S Food and Drug Administration (FDA) for the treatment of metastatic kidney cancer and is a standard treatment of this disease. At the present time, IL-2 is the only therapy for kidney cancer that can produce a remission of disease that lasts after treatment is completed. However, most patients who receive IL-2 do not benefit and all patients experience potentially dangerous side effects. Recent research has suggested that certain patients may respond better to IL-2 than others. The Cytokine Working Group is currently conducting a clinical trial that aims to identify and confirm this research and narrow the application of IL-2 to those patients most likely to benefit.
Detailed description
OBJECTIVES: Primary * To determine, in a prospective fashion, if the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and good pathologic predictive features is significantly higher than a historical, unselected patient population. Secondary * To determine, in a prospective fashion, the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and poor pathologic predictive features and to compare this response rate to the response rate of patients with good pathologic predictive features. * To determine if components of other predictive and prognostic models (e.g MSKCI or UCLA criteria) can help to further define the optimal population to receive high-dose IL2 for metastatic renal cell carcinoma. * To identify features of the baseline immune function (arginine, arginase, T cell zeta chain) of patients with metastatic renal cell carcinoma that are associated with response to high-dose IL-2. * To identify new proteins or patterns of gene expression that might be associated with high-dose IL-2 responsiveness in order to further narrow the application of IL-2 therapy to those who will benefit the most.
Interventions
DRUGHD IL2
Sponsors
City of Hope National Medical Center
Providence Cancer Center, Earle A. Chiles Research Institute
Dartmouth-Hitchcock Medical Center
Indiana University
Loyola University
Our Lady of Mercy Medical Center
Roswell Park Cancer Institute
University of California, Los Angeles
University of Cincinnati
University of Pittsburgh
University of Virginia
Vanderbilt University
Wayne State University
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed renal cell carcinoma that is metastatic or unresectable. * If patients have measurable disease restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology. * Patients must provide access to tissue blocks containing adequate tumor for interpretation and analysis. * Patients must have measurable disease. * Patients must have good performance status (ECOG 0 or 1; Karnofsky PS 100-80%). * Patients must have adequate organ function. * Patients must have no contraindication of vasopressor agents. * Patients must be ≥ 18 years of age.
Exclusion criteria
* Patients who have received systemic therapy for metastatic disease. * Patients with organ allografts. * Patients who require or are likely to require systemic corticosteroid therapy for intercurrent illness. * Patients with any significant medical disease other than the malignancy (e.g. COPD, patients with ascites or pleural effusions), which in the opinion of the investigator would significantly increase the risk of immunotherapy. * Patients with a history of another malignancy within the past 5 years other than surgically cured non-melanoma skin cancer, carcinoma-in-situ or Stage I carcinoma of the cervix.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response in ISM Good Risk Group | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by investigator assessment of radiographs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate in ISM Poor Risk Group | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on treatment on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Objective Response Rate (Independent Assessment) | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks.. Response status was determined by independent assessment of radiographs. |
| Overall Survival | Participants were followed for survival up to 7 years. | Overall survival based on the Kaplan-Meier method is defined as the time from treatment start to date of death or censored at the date of last documented contact. |
| Objective Response Rate by MSKCC Risk Group | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Objective Response Rate by UCLA SANI Score | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Objective Response Rate by Tumor Type | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| 3-Year Progression-Free Survival Rate | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Relevant for this endpoint was disease status at 3 y. | 3-year progression-free survival rate is defined as the proportion of patients absent death or progression based on WHO criteria by 3 years since time of treatment start. PD is a \>/=25% increase in the sum of products of the perpendicular diameters of all measurable lesions. Further, PD is the appearance of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. |
| Objective Response Rate by CA-9 Score (CAIX Classification) | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Objective Response Rate by PD-L1 Tumor | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Objective Response Rate by B7-H3 Tumor | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Objective Response Rate by CA-9 SNP | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262). | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs. |
| Progression-Free Survival | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Median survival follow-up was X months (95% CI: ). | Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from treatment start to date of disease progression (PD) or death. Per WHO criteria: PD is a \>/=25% increase in the sum of products of the perpendicular diameters of all measurable lesions. Further, PD is the appearance of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. Participants who were event-free were censored at the date of their last disease evaluation. |
| Objective Response Rate by Clear Cell Histology Risk Group | Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Response status was confirmed by an independent assessment of radiographs. Participants received up to 3 courses of 12 weeks duration each. | The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. |
Countries
United States
Participant flow
Recruitment details
Participants enrolled from 13 institutions between November 2006 and November 2008.
Participants by arm
| Arm | Count |
|---|---|
| HD IL2 Participants received high-dose (HD) IL2, 600,000 IU/kg/dose (Prometheus Laboratories Inc.) i.v. every 8 hours for 5 days (maximum of 14 doses) beginning on day 1 and again on day 15. One course generally consisted of 5 days of treatment, 9 days of rest, 5 more days of treatment, and 9 weeks of rest, followed by up to two additional courses of HD IL2 for patients who benefited and tolerated most of the planned IL2 doses. A treatment delay of up to 4 weeks was allowed for resolution of side effects between courses. Patients were eligible to receive a maximum of three courses of treatment. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Achieved Stable Disease | 7 |
| Overall Study | Adverse Event | 9 |
| Overall Study | Death | 2 |
| Overall Study | Disease progression | 52 |
| Overall Study | Misc | 15 |
| Overall Study | Other | 1 |
| Overall Study | Physician Decision | 18 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | HD IL2 |
|---|---|
| Age, Continuous | 56 years |
| ISM Risk Group Good | 74 Participants |
| ISM Risk Group Poor | 43 Participants |
| ISM Risk Group Unknown | 3 Participants |
| MSKCC Risk Group Favorable | 23 Participants |
| MSKCC Risk Group Intermediate | 84 Participants |
| MSKCC Risk Group Poor | 13 Participants |
| Region of Enrollment United States | 120 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 85 Participants |
| UCLA SANI Score High | 8 Participants |
| UCLA SANI Score Intermediate | 102 Participants |
| UCLA SANI Score Low | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 120 |
| other Total, other adverse events | 2 / 120 |
| serious Total, serious adverse events | 15 / 120 |
Outcome results
Primary
Objective Response in ISM Good Risk Group
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by investigator assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data for ISM analysis and classified as ISM good risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response in ISM Good Risk Group | .23 proportion of participants |
p-value: 0.042exact binomial test
Secondary
3-Year Progression-Free Survival Rate
3-year progression-free survival rate is defined as the proportion of patients absent death or progression based on WHO criteria by 3 years since time of treatment start. PD is a \>/=25% increase in the sum of products of the perpendicular diameters of all measurable lesions. Further, PD is the appearance of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Relevant for this endpoint was disease status at 3 y.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | 3-Year Progression-Free Survival Rate | .108 proportion of participants |
Secondary
Objective Response Rate by B7-H3 Tumor
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by B7-H3 Tumor | .11 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by B7-H3 Tumor | .29 proportion of participants |
Comparison: Objective response rates were compared between B7-H3 tumor subgroupsp-value: 0.08Fisher Exact
Secondary
Objective Response Rate by CA-9 Score (CAIX Classification)
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by CA-9 Score (CAIX Classification) | .33 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by CA-9 Score (CAIX Classification) | .22 proportion of participants |
Comparison: Objective response rates were compared between CA-9 score subgroupsp-value: 0.19Fisher Exact
Secondary
Objective Response Rate by CA-9 SNP
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by CA-9 SNP | .20 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by CA-9 SNP | .33 proportion of participants |
Comparison: Objective response rates were compared between CA-9 SNP subgroupsp-value: 0.28Fisher Exact
Secondary
Objective Response Rate by Clear Cell Histology Risk Group
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Response status was confirmed by an independent assessment of radiographs. Participants received up to 3 courses of 12 weeks duration each.
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by Clear Cell Histology Risk Group | .27 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by Clear Cell Histology Risk Group | .24 proportion of participants |
| Poor MSKCC Risk Group | Objective Response Rate by Clear Cell Histology Risk Group | .28 proportion of participants |
Comparison: Objective response rates were compared between clear cell histology subgroupsp-value: 0.89Fisher Exact
Secondary
Objective Response Rate by MSKCC Risk Group
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by MSKCC Risk Group | .22 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by MSKCC Risk Group | .25 proportion of participants |
| Poor MSKCC Risk Group | Objective Response Rate by MSKCC Risk Group | .31 proportion of participants |
Comparison: Objective response rates were compared between MSKCC subgroups.p-value: 0.89Fisher Exact
Secondary
Objective Response Rate by PD-L1 Tumor
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by PD-L1 Tumor | .19 proportion of patients |
| Intermediate MSKCC Risk Group | Objective Response Rate by PD-L1 Tumor | .50 proportion of patients |
Comparison: Objective response rates were compared between PD-L1 tumor subgroupsp-value: 0.01Fisher Exact
Secondary
Objective Response Rate by Tumor Type
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by Tumor Type | .26 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by Tumor Type | .00 proportion of participants |
Comparison: Objective response rates were compared between tumor type subgroupsp-value: 0.33Fisher Exact
Secondary
Objective Response Rate by UCLA SANI Score
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate by UCLA SANI Score | .20 proportion of participants |
| Intermediate MSKCC Risk Group | Objective Response Rate by UCLA SANI Score | .27 proportion of participants |
| Poor MSKCC Risk Group | Objective Response Rate by UCLA SANI Score | .00 proportion of participants |
Secondary
Objective Response Rate (Independent Assessment)
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks.. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate (Independent Assessment) | .25 proportion of participants |
Comparison: Test against the historical ORR was conducted in the overall study population as secondary analyses.p-value: 0.0014exact binomial test
Secondary
Objective Response Rate in ISM Poor Risk Group
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on treatment on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by independent assessment of radiographs.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
Population: The analysis dataset is comprised of all treated patients with available tumor tissue/data for ISM analysis and classified as ISM poor risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISM Good Risk Group | Objective Response Rate in ISM Poor Risk Group | .23 proportion of participants |
Comparison: Objective response rates were compared between ISM good and poor risk subgroups. ISM good risk ORR reported under primary endpoint.p-value: 0.39Fisher Exact
Secondary
Overall Survival
Overall survival based on the Kaplan-Meier method is defined as the time from treatment start to date of death or censored at the date of last documented contact.
Time frame: Participants were followed for survival up to 7 years.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ISM Good Risk Group | Overall Survival | 42.8 months |
Secondary
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from treatment start to date of disease progression (PD) or death. Per WHO criteria: PD is a \>/=25% increase in the sum of products of the perpendicular diameters of all measurable lesions. Further, PD is the appearance of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. Participants who were event-free were censored at the date of their last disease evaluation.
Time frame: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Median survival follow-up was X months (95% CI: ).
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ISM Good Risk Group | Progression-Free Survival | 4.2 months |