Phase II Trial of PS-341 in Patients With Renal Cell Cancer: A University of Chicago Phase II Consortium Study

2004 ◽  
Vol 22 (1) ◽  
pp. 115-119 ◽  
Author(s):  
Nancy B. Davis ◽  
David A. Taber ◽  
Rafat H. Ansari ◽  
Christopher W. Ryan ◽  
Christopher George ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Renal Cell Cancer ◽  
Whole Blood ◽  
Renal Cell ◽  
Cell Cancer ◽  
Objective Response ◽  
Proteasome Inhibition ◽  
Significant Activity ◽  
Grade 3

PurposeDetermine response rate, time to disease progression, and toxicity of the proteasome inhibitor PS-341 in patients with stage IV renal cell cancer.Patients and MethodsPS-341 1.5 mg/m2was administered intravenously twice weekly for 2 weeks every 21 days. Dose escalation to 1.7 mg/m2ensued in the absence of grade 3 to 4 toxicities. Re-evaluation took place after three cycles. To assess proteasome inhibition, patients were randomly assigned to tumor core biopsy either before the first dose or after the third cycle of PS-341. Additionally, whole blood was collected at the same time intervals.ResultsTwenty-three patients were enrolled; 21 were assessable for response. Two patients were never treated (one patient refused treatment and one had insufficient tumor for biopsy). Eighteen patients completed at least three cycles of therapy; three patients experienced disease progression after two cycles. Grade 4 toxicities were arthralgia, diarrhea, and vomiting. Grade 3 toxicities included thrombocytopenia with one hemorrhage, anemia, febrile neutropenia, gastrointestinal toxicity, pain, fatigue, neuropathy (one sensory, one mixed sensorimotor), and electrolyte disturbances. Grade 1 to 2 neuropathy occurred in seven patients. One case of thrombosis and one case of pleural effusion occurred. Only one objective response was seen. Proteasome activity was measured by specific chymotryptic activity (SpA) and chymotryptic/tryptic activity (ChT:T). After PS-341, there was a decrease in mean whole blood SpA and ChT:T (P = .07 and .11, respectively).ConclusionEvidence is lacking for clinically significant activity of PS-341 in metastatic renal cell cancer. Insufficient biopsy and whole blood sample numbers preclude conclusions regarding proteasome inhibition within tumor. Further evaluation in this disease setting is not recommended.

Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer

2009 ◽  
Vol 27 (27) ◽  
pp. 4469-4474 ◽  
Author(s):  
Giuseppe Di Lorenzo ◽  
Giacomo Cartenì ◽  
Riccardo Autorino ◽  
Gianni Bruni ◽  
Marianna Tudini ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Second Line ◽  
Metastatic Renal Cell Cancer ◽  
Grade 3

Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.

A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1942-1946 ◽  
Author(s):  
John E. Janik ◽  
Langdon L. Miller ◽  
Edward L. Korn ◽  
Diane Stevens ◽  
Brendan D. Curti ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Complete Regression ◽  
Protective Effects ◽  
Gm Csf ◽  
Grade 3 ◽  
To Receive

Abstract We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 μg/m2 daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 μg/m2 twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P = .0074). The mean duration of neutropenia was reduced by GM-CSF priming: grade 3 neutropenia from 5.2 ± 0.7 to 2.8 ± 0.7 days (P = .0232) and grade 4 neutropenia from 2.7 ± 0.6 to 1.1 ± 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy.

A phase II trial of everolimus and bevacizumab in advanced non-clear cell renal cell cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 411-411
Author(s):  
Martin Henner Voss ◽  
Yingbei Chen ◽  
Joshua Chaim ◽  
Devyn Taylor Coskey ◽  
Kaitlin Woo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Primary Endpoint ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Trial ◽  
Cell Cancer ◽  
Objective Response ◽  
Histologic Subtype ◽  
Limited Effectiveness

411 Background: VEGF- and mTOR-directed therapies achieve inferior outcomes in patients (pts) with advanced non-clear cell renal cell cancer (ncRCC) as compared to clear cell RCC. Limited effectiveness of monotherapy supports the study of combination regimens, and a phase II trial of everolimus (E) + bevacizumab (B) was conducted in pts with metastatic ncRCC. Methods: Treatment-naïve pts received E + B at standard doses until progression or intolerance to therapy. The primary endpoint was progression free survival (PFS) with the goal to see 22 of 34 pts progression-free on treatment >6 months (mo). Correlative analyses include next generation sequencing (NGS) from tumor and germline across 341 genes of interest, as well as immunohistochemistry (IHC) for markers of mTOR activation and vessel density. Results: 34 pts were enrolled, all are evaluable (median follow up 11.2 mo). The most common histologic subtype was unclassified RCC (URCC, n=23), the majority of which had papillary growth as a major component (URCC with papillary features, n=14). Other variants included chromophobe (n=5), papillary (n=4), and medullary RCC (n=2). 19 pts achieved PFS >6 mo; 8 continue on treatment. PFS varied by histology (p<0.001), and objective response rates (ORR) were higher in pts with significant papillary (7 of 18) or chromophobe (2 of 5) elements, than for the remaining pts (1 of 11). Presence of a major papillary component was associated with treatment benefit across the entire cohort (Table), particularly in the subgroup of URCC, where this feature correlated with ORR (43 vs. 11%), median PFS (12.9 vs. 1.9mo) and OS (18.5 vs. 9.3 mo) (p<0.001). IHC markers did not correlate with treatment effect. NGS was performed on 33 cases. Conclusions: ncRCC represent a heterogeneous group of malignancies. This study did not reach its primary endpoint, yet it suggests efficacy for E+B in patients with ncRCC characterized by papillary features. Genomic tumor and germline analysis is being performed to help define the underlying biology. Clinical trial information: NCT01399918. [Table: see text]

Camrelizumab plus famitinib malate in patients with advanced renal cell cancer and unresectable urothelial carcinoma: A multicenter, open-label, single-arm, phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5085-5085
Author(s):  
Yuan-Yuan Qu ◽  
Hongqian Guo ◽  
Hong Luo ◽  
Qing Zou ◽  
Ninazeng Xing ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Antitumour Activity ◽  
Cell Cancer ◽  
Objective Response ◽  
Open Label ◽  
Genitourinary Cancers ◽  
Grade 3

5085 Background: Camrelizumab (SHR-1210) is a humanised anti-PD-1 antibody. Famitinib malate is a tyrosine kinase inhibitor (TKI) against VEGFR-2, PDGFR, c-kit, and FGFR. This is an ongoing, open label, multi-center Phase II study to assess the preliminary efficacy and safety of camrelizumab in combination with famitinib malate in patients (pts) with genitourinary cancers and gynecologic cancers. Here we just report genitourinary cancers results. Methods: Eligible pts were aged 18 or older, who had advanced clear-cell renal-cell carcinoma with their primary tumour resected or unresectable urothelial carcinoma, had an ECOG performance status of 0-1and measurable disease. Previous system treatments were allowed (excluding prior PD-1/PD-L1 inhibitors or famitinib treatment). Famitinib 20 mg was administered orally once daily with SHR-1210 200 mg given intravenously every 3 weeks. We assessed antitumour activity and safety in all pts who received at least one dose treatment. The primary end point was objective response rate (ORR) per RECIST v1.1. Results: From 23 Jan 2019 to 24 Jun2019, 35 pts were enrolled (25 with RCC, 10 with UC). Median previous treatment line was 1 (range, 1-4), and 50.0% of pts had received ≥2 prior therapies in RCC, all pts received one or more-line therapies in UC. At the data cut-off date (Dec 31, 2019), after at least 6 months follow-up, 22 (63%) pts were still receiving study treatment. The most common reason for discontinuing treatments was disease progression (n = 10). 16 pts achieved a confirmed response, all were partial response, with 8 additional > 24 weeks stable disease. the ORR was 52.0% (13/25, 95% CI 31.3% to 72.2%) in RCC and 30.0% (3/10) in UC, the disease control rate was 84.0% (21/25) in RCC and 70.0% in UC. 13/16 confirmed PR pts were still on treatment, the median duration of response is not reached. The most common grade 3-4 treatment-related AEs (TRAEs) were hypertension (17.1%), proteinuria (11.4%), platelet count decreased (8.6%), hand-foot syndrome (8.6%) and anemia (5.7%). Immune-related adverse events were observed in 7 pts (20%) of 35 pts, 1 pt (2.9%) with grade 3 enteritis. Conclusions: The camrelizumab with famitinib combination appeared to show encouraging activity in pts with heavy-treated RCC and UC, and the safety profile of the combination seemed to be manageable and consistent with that of each drug alone. This combination represented a novel potential treatment option for these settings and warranted further investigation. Clinical trial information: NCT03827837 .

Metastatic renal cell cancer treated with low-dose interleukin-2. A phase-II multicentre study

1989 ◽  
Vol 16 ◽  
pp. 111-113 ◽  
Author(s):  
G. Stoter ◽  
S.D. Fosså ◽  
C. Rugarli ◽  
M. Symann ◽  
C. Jasmin ◽  
...  
Keyword(s):  
Multicentre Study ◽  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Low Dose ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Metastatic Renal Cell Cancer

Lack of efficacy of recombinant human interleukin-6 in patients with advanced renal cell cancer: results of a phase II study

1998 ◽  
Vol 34 (5) ◽  
pp. 754-756 ◽  
Author(s):  
M Schuler ◽  
U Bruntsch ◽  
E Späth-Schwalbe ◽  
H Schrezenmeier ◽  
C Peschel ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Interleukin 6 ◽  
Renal Cell ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Advanced Renal Cell Cancer

scholarly journals Phase Ii Study of Individualized Sunitinib As First-Line Therapy for Metastatic Clear Cell Renal Cell Cancer (Mrcc)

2014 ◽  
Vol 25 ◽  
pp. iv292 ◽  
Author(s):  
G.A. Bjarnason ◽  
B. Naveen ◽  
E. Winquist ◽  
C.K. Kollmannsberger ◽  
C. Canil ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy.

1990 ◽  
Vol 8 (10) ◽  
pp. 1657-1663 ◽  
Author(s):  
M Hirsh ◽  
A Lipton ◽  
H Harvey ◽  
E Givant ◽  
K Hopper ◽  
...  
Keyword(s):  
Phase I ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Phase I Study ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Interferon Alfa ◽  
Significant Activity ◽  
Outpatient Therapy ◽  
Ifn Alpha

Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.

Phase II Trial of Weekly Intravenous Gemcitabine With Continuous Infusion Fluorouracil in Patients With Metastatic Renal Cell Cancer

2000 ◽  
Vol 18 (12) ◽  
pp. 2419-2426 ◽  
Author(s):  
Brian I. Rini ◽  
Nicholas J. Vogelzang ◽  
Mary C. Dumas ◽  
James L. Wade ◽  
David A. Taber ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Renal Cell ◽  
Response Rate ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Metastatic Rcc

PURPOSE: To determine the clinical response rate of the combination of weekly intravenous (IV) gemcitabine with continuous infusion fluorouracil (5-FU) in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Between June 1998 and February 1999, 41 patients with metastatic RCC were enrolled onto this multi-institutional phase II study of gemcitabine 600 mg/m2 over 30 minutes on days 1, 8, and 15 and 5-FU 150 mg/m2/d via continuous IV infusion through a permanent catheter on days 1 to 21 of a 28-day cycle. Patients had a Cancer and Leukemia Group B performance status of 0 or 1, with a median time since diagnosis of metastatic disease of 10 months (range, 0 to 129 months). Thirty-three patients (80%) had multiple metastatic sites, and 34 patients (83%) had prior chemotherapy or immunotherapy. RESULTS: Of the 39 assessable patients, there were no complete responses but seven partial responses (objective response rate = 17%; 95% confidence interval, 8% to 34%). Five minor responses (25% to 50% decreased tumor size) were also observed. The duration of response for the seven partial responders was 2, 3, 7, 8, 10, 11, and 14 months. Median progression-free survival for the gemcitabine/5-FU group was 28.7 weeks versus 8 weeks for a similar cohort of patients treated on previous phase II studies at the University of Chicago (P = .008). The regimen was well tolerated, with fatigue, mucositis, nausea/vomiting, and grade 2 hematologic toxicities being most common. CONCLUSION: Weekly gemcitabine with continuous infusion 5-FU is an active combination in patients with metastatic RCC. Therapy was well tolerated and produced an improvement in progression-free survival over historical controls.

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