Phase II ECOG trial of atrasentan in advanced renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5102-5102 ◽  
Author(s):  
J. Manola ◽  
M. Carducci ◽  
S. Nair ◽  
G. Liu ◽  
S. Rousey ◽  
...  
Keyword(s):  
Adverse Events ◽  
Bone Metastases ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Disease Status ◽  
Supraventricular Arrhythmia ◽  
Duration Of Treatment ◽  
Measurable Disease ◽  
Grade 3 ◽  
Ecog Ps

5102 Background: Atrasentan, an oral selective endothelin A receptor antagonist, demonstrated activity in patients with RCC included in Phase I studies. Based on these preliminary findings, a phase II study was undertaken in patients with measurable or nonmeasurable (bone only) metastatic RCC. Methods: Patients with locally recurrent or metastatic disease were stratified on disease status (measurable or bone only metastases) and prior immunotherapy. Eligible patients also had no prior chemotherapy, no more than 1 prior immunotherapy, and ECOG PS 0, 1, or 2. Prior nephrectomy was permitted. Patients received atrasentan 10 mg/day po until progression or unacceptable toxicity. Standard RECIST criteria were used to assess response. The primary endpoint was the progression-free rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A two-stage design was used for cohorts with no prior immunotherapy. Results: Between July 2003 and July 2005, 98 patients were registered. Four patients were ineligible and 1 withdrew before treatment. Median duration of treatment was 10 weeks (range, 2 to 107 weeks). Toxicities were mild, with 73% of patients reporting no Grade 3 or higher treatment- related adverse events. Grade 4 adverse events included neutropenia (n=3), dyspnea (n=2), thrombosis and supraventricular arrhythmia (n=1 each). Six-month progression-free rates (90% CI) were 14% (6 - 25%), 0% (0 - 39%), 12% (3 - 28%) and 17% (5 - 38%) respectively for patients with prior immunotherapy and measurable disease (n=44), prior immunotherapy and bone metastases only (n=6), no prior immunotherapy and measurable disease (n=25), and no prior immunotherapy and bone metastases only (n=18). Median progression-free survival was 2.3 months (95% CI, 2.0 - 3.5 months). Conclusions: While well-tolerated, atrasentan did not yield 6-month progression-free rates that would support its use as first-line monotherapy in patients with advanced RCC. No significant financial relationships to disclose.

A phase II study of vorolanib (CM082) in combination with toripalimab (JS001) in patients with advanced mucosal melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10040-10040 ◽  
Author(s):  
Lu Si ◽  
Xinan Sheng ◽  
Lili Mao ◽  
Caili Li ◽  
Xuan Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Clinical Activity ◽  
Effective Treatment Option ◽  
Grade 3 ◽  
Ecog Ps

10040 Background: Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1) with clinical activity in metastasis melanoma but not in its mucosal subtype. In this phase II study (NCT03602547), we investigated the safety and efficacy of CM082 in combination with JS001 in patients (pts) with advanced mucosal melanoma. Methods: The study enrolled pts from 18 to 75 years-old with histologically confirmed metastatic mucosal melanoma, ECOG PS 0-1, no prior systemic anti-cancer treatment. Eligible pts were treated with CM082 tablet (150 or 200 mg once daily) combined with JS001 (240mg every 2 weeks, IV, Q2W) until confirmed disease progression or unacceptable toxicity. Clinical response was evaluated every 8 week. The primary endpoint was overall response rate (ORR) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of remission (DOR), and time to first remission (TTR) according to RECIST v1.1 and iRECIST. The safety was also assessed. Results: Between July 2018 and April 12, 2019, 40 pts (19 pts in 150mg group; 21 pts in 200mg group) were enrolled and 38 pts were evaluable for tumor response (150mg n = 18, 200mg n = 20), with 4 (22.2%) confirmed partial response (PR), 6 (33.3%) stable disease (SD) and 8 (44.4%) progression disease (PD) in the 150mg CM082 group; 3 (15%) PRs (including 2 unconfirmed), 10 (50%) SD, and 7 (35%) PD were reported in the 200mg CM082 group. Tumors shrank in 10 pts (56%) in the 150mg group and 10 pts (50%) in the 200mg group. At data cut-off (November 28, 2019), 29 pts had PFS events (150mg n = 12; 200mg n = 17). The median PFS was 5.7 (95% CI 2.0, NE) months and 5.6 (1.9, 7.7) months in the two groups, respectively. The most common treatment-related adverse events (AEs) were grade 1 or 2, including leukopenia, elevated LDH, increased ALT, neutropenia, increased AST, and elevated GGT. Common grade 3 or higher adverse events ( > 10%) were increased ALT (12 pts, 30%), increased AST (11 pts, 27.5%), neutropenia (6 pts, 15%) and elevated GGT (6 pts, 15%). Eight pts had 9 serious AEs (SAEs). The study is still ongoing and more data will be presented in the future. Conclusions: PFS benefit was observed in both 150mg and 200mg subgroups. This study demonstrated potentially improved efficacy with predictable toxicities of CM082 in combination with JS001 therapy, which may be an effective treatment option for pts with advanced mucosal melanoma. Clinical trial information: NCT03602547.

A phase II study of patupilone in patients (pts) with metastatic castration- resistant prostate cancer (CRPC) who have progressed after docetaxel

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5139-5139 ◽  
Author(s):  
E. K. Beardsley ◽  
F. Saad ◽  
B. Eigl ◽  
P. Venner ◽  
S. Hotte ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Disease Response ◽  
Measurable Disease ◽  
Psa Response ◽  
Grade 3 ◽  
Ecog Ps

5139 Background: Chemotherapy for pts with CRPC who have progressed after docetaxel remains to be defined. Patupilone is an epothilone with broad spectrum pre-clinical activity including in taxane resistant models. Methods: Multicenter, 2-stage design. Pts with metastatic CRPC with progressive disease during or within 6 months of receiving docetaxel were eligible. Patupilone was initially given 10mg/m 2 IV every 3 weeks. PSA response rate (≥50% decline) was the primary endpoint (H0 = 15%, H1 = 25%, α = 0.1, β = 0.2). Secondary endpoints were measurable disease response, serial pain and analgesics scores, progression free survival (PFS) and overall survival (OS). Results: 83 pts were enrolled from March 2007-June 2008. 401 cycles administered (median 5, range 1–15). Baseline characteristics (range): median age 67 (47–85), PSA 212 (2.6–11520), hemoglobin 118 (89–160), median time to progression after docetaxel 1.0 months (0.0–6.0), number of prior chemotherapy regimens 1:2:3+ in 45:28:10 pts, ECOG PS 0–1:2 in 73:10 pts, disease in bone/lymph nodes/viscera in 76/47/14 pts respectively. In the first 6 pts, gastrointestinal serious adverse events (AE) occurred in 4 pts (diarrhea and vomiting) which lead to a dose reduction of patupilone to 8 mg/m2 for subsequent patients. Grade 3/4 related adverse events at this dose included fatigue (16%), diarrhea (13%) and anorexia (5%). There were no grade 3/4 hematologic AEs. In 78 pts evaluable for PSA response, PSA declines of ≥30% and ≥50% have occurred in 44/78 (56%) and 35/78 (45%) with a confirmed PSA response in 25 pts (32%). Partial response occurred in 5% and stable disease in 64% of 44 evaluable pts. Pain response (2 point decline on 6 point scale) occurred in 36 (51%) of 71 pts eligible for analysis. Median PFS for PSA and non-PSA outcomes (measurable disease/symptomatic progression or death) was 7.6 months (3.7–11.5) and 5.6 months (3.9–7.3) respectively. Follow up for OS is continuing. Conclusions: Patupilone 8 mg/m2 every 3 weeks was well tolerated and associated with encouraging PFS, PSA and pain responses in pts with docetaxel resistant/refractory disease. Further investigation of patupilone in this population is warranted. [Table: see text]

Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
M. H. Moehler ◽  
P. Thuss-Patience ◽  
D. Arnold ◽  
W. Grothe ◽  
A. Stein ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Response Assessment ◽  
Metastatic Gastric Cancer ◽  
Phase Ii Trials ◽  
Grade 3 ◽  
Ecog Ps

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1133-1133 ◽  
Author(s):  
S. K. Taylor ◽  
S. Chia ◽  
S. Dent ◽  
M. Clemons ◽  
P. Grenci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Grade 3

1133 Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer. [Table: see text]

Final results of a phase II study of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic or recurrent squamous cell cancer of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5592-5592 ◽  
Author(s):  
George R. Blumenschein ◽  
Bonnie S. Glisson ◽  
Charles Lu ◽  
Anita Lyn Sabichi ◽  
Lawrence E. Ginsberg ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Angiogenic Growth Factors ◽  
Current Standard ◽  
Hand Foot Syndrome ◽  
Current Standard Treatment ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

5592 Background: Cytotoxic chemotherapy (CT) is the current standard treatment for metastatic/recurrent SCCHN. The prognosis for these patients (PTS) is poor with a median progression free survival (PFS) of 4 months with CT. Survival in PTS with SCCHN may correlate inversely with the number of angiogenic growth factors secreted. Sorafenib is a potent inhibitor of c-Raf, b-Raf, VEGFR-1/2/3 and PDGFR-β. To investigate the hypothesis that a multi-targeted TKI added to chemotherapy would improve outcomes in patients with metastatic/recurrent SCCHN, we performed a phase II trial of   paclitaxel and carboplatin and sorafenib (PCS). Methods: PTS were required to have ECOG PS 0-1, measurable disease, controlled blood pressure, and may have received one regimen of induction, concomitant or adjuvant CT, but not CT for recurrent/metastatic disease. Sites of primary disease excluded nasopharynx and paranasal sinus. Treatment consisted P 200mg/m2 and C AUC 6 intravenously on day 1 followed by S 400 mg orally bid (days 2-19) in every 3-week cycles.  Primary endpoint was PFS, targeting median PFS of 6 months (M). Secondary endpoints include overall survival (OS), response rate (RR), exploratory biomarkers, and toxicity. Results: Forty-eight PTS with SCCHN were enrolled with 44 PTS evaluable for PFS and response using RECIST. Median age: 56 years (22-79 years), 89% male, median ECOG PS 1.  Median follow-up was 24.1 M.  RR was 55% (n=24), disease control rate was 84% (n=37), median PFS was 8.51 M (95% CI: 5.98 ~ 13 months), and median OS was 22.6 M (95% CI: 13.1 - NA months). Grade ³3 treatment related toxicities included hand-foot syndrome (n=10), neutropenia (n=5), pain (n=6), elevated lipase (n=4), elevated amylase (n=3), anemia (n=3), fatigue (n=2), hypertension (n=2), neuropathy (n=2), febrile neutropenia (n=2), and thrombocytopenia (n=2).  Conclusions: The combination of PCS was well tolerated and had encouraging activity in recurrent/metastatic SCCHN. Blood-based and tissue biomarkers are being analyzed.  Final outcomes, toxicity, and correlative biomarker data will be reported.

Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4692-TPS4692 ◽  
Author(s):  
Mario A. Eisenberger ◽  
Anne-Claire Hardy-Bessard ◽  
Loic Mourey ◽  
Paul N. Mainwaring ◽  
Daniel Ford ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Measurable Disease ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.

Phase II study of ipilimumab and nivolumab (ipi/nivo) in metastatic uveal melanoma (UM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9522-9522 ◽  
Author(s):  
Meredith Pelster ◽  
Stephen K. Gruschkus ◽  
Roland Bassett ◽  
Dan S. Gombos ◽  
Michael Shephard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Duration Of Treatment ◽  
Safety And Efficacy ◽  
One Year ◽  
Ecog Ps

9522 Background: UM is the most common primary intraocular malignant tumor in adults. Approximately 40-50% of patients (pts) with UM will ultimately develop metastatic disease. There is currently no standard approach for metastatic UM. Early studies of single agent immunotherapy (IO) in metastatic UM have yielded meager results. Combination checkpoint inhibitor IO has the potential to improve response rates and survival. Herein, we report the safety and efficacy of ipi/nivo in metastatic UM. Methods: We performed a single-arm phase II study in metastatic UM (CA184-187) for pts with at least 1 measureable lesion and ECOG PS 0-1. Any number of prior treatments were permitted. Pts received nivolumab 1mg/kg IV plus ipilimumab 3mg/kg IV every 3 weeks for a total of 4 doses; maintenance nivolumab was dosed 3mg/kg every 2 weeks or 480mg IV every 4 weeks. The primary efficacy endpoint was best overall response rate (BORR) as determined by irRC. Secondary endpoints were median progression free survival (PFS), median overall survival (OS), and one-year OS. Results: As of the January 31, 2019 data cutoff, 39 pts were enrolled. 35 pts received at least one treatment and were evaluable for toxicity. 5 pts were inevaluable for response due to lack of follow-up imaging, leaving 30 pts evaluable for efficacy. 32 pts (91%) experienced any adverse event (AE), and 29 pts (83%) experienced any treatment related AE (TRAE). Grade 3-4 TRAEs occurred in 14 pts (40%). 10 pts (29%) were removed from the study due to AEs. There were no treatment-related deaths. Median duration of follow up is 60.5 weeks. 19 pts (63%) completed all 4 cycles of ipi/nivo; median duration of treatment was 16 weeks. The BORR was partial response for 5 pts (17%), stable disease (SD) for 16 pts (53%), and progression of disease for 9 pts (30%). 8 pts had SD for at least 6 months. Median PFS was 26 weeks. Median OS was 83 weeks (1.6 years), and one-year OS was 62%. Conclusions: Full results of ipi/nivo safety and efficacy including immune-related AE and clinical characteristics of the responders will be presented at the meeting. Preliminary translational tumor work including RNA analysis has been performed on a subset of responders. Clinical trial information: NCT01585194.

Phase II trial of bevacizumab and everolimus in the treatment of patients with metastatic melanoma: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9027-9027 ◽  
Author(s):  
J. D. Peyton ◽  
D. R. Spigel ◽  
H. A. Burris ◽  
C. Lane ◽  
M. Rubin ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Treatment Regimens ◽  
Intercurrent Illness ◽  
Eligibility Requirements ◽  
Grade 3 ◽  
Ecog Ps

9027 Background: Metastatic melanoma remains resistant to therapy. Anti-angiogenesis agents and m-TOR inhibitors have shown modest activity as single agents. In this multicenter phase II trial, we evaluated the combination of bevacizumab and everolimus in the treatment of patients with metastatic melanoma. Methods: Patients with unresectable metastatic melanoma with ECOG PS 0–2 were eligible. Up to 2 previous treatment regimens were allowed; patients previously treated with angiogenesis or m-TOR inhibitors were excluded. Additional eligibility requirements: adequate organ function, no CNS involvement, standard bevacizumab exclusions. All patients received bevacizumab 15mg/kg IV q 3 weeks, and everolimus 10mg po daily. Patients were evaluated every 6 weeks, and treatment continued until disease progression. Results: Between February 2008 and October 2008, 56 patients were enrolled; the first 31 patients are included in this interim report. The median age was 71 years (range 36 to 89 years); 19 patients (61%) had visceral metastases; 0/1/2 previous regimens, 12/11/8 patients; ECOG PS 0/1/2, 17/11/1. 28 patients (90%) received at least 6 weeks of treatment; 3 patients withdrew prior to 6 weeks (toxicity, 2 patients; intercurrent illness, 1 patient). 1 of 28 evaluable patients (4%) had a PR. However, 19 additional patients (68%) had stable disease (15 of these patients had measurable decrease in tumor size), for a disease control rate of 72%. 14 patients remain on treatment, after treatment durations of 2 - 7.5 months. After a median followup of 5 months, the median progression-free survival is 3.5 months (95% CI 2.4 - 5.4 months). Bevacizumab/everolimus was generally well tolerated. 1 patient withdrew because of interstitial pneumonitis (reversible) and 1 patient had a fatal MI, possibly bevacizumab-related. Grade 3 mucositis occurred in 13%; other grade 3 toxicities occurred in < 10% of patients. Conclusions: The combination of bevacizumab and everolimus was well tolerated and has activity in patients with metastatic melanoma. Updated results in all 56 patients will be presented. [Table: see text]

A phase II study on third-line chemotherapy combined bevacizumab with S-1 for metastatic colorectal cancer with mutated KRAS: SAVIOR study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 552-552
Author(s):  
Akinori Takagane ◽  
Yasuhiro Miyake ◽  
Kouji Kobayashi ◽  
Naoki Nagata ◽  
Atsushi Sato ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Dihydropyrimidine Dehydrogenase ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Antitumor Effects ◽  
Grade 3 ◽  
Line Chemotherapy

552 Background: Anti-Epidermal growth factor receptor (EGFR) antibody therapy is expected to be effective in treatment for metastatic colorectal cancer (mCRC) with wild-type KRAS, but for mCRC with mutated KRAS, no salvage treatment has been established. We performed a phase II clinical study on 3rd-line chemotherapy combined bevacizumab with S-1, an oral fluorinated pyrimidine preparation containing a dihydropyrimidine dehydrogenase inhibitor, and bevacizumab for mCRC resistant to oxaliplatin and irinotecan. Methods: Subjects were mCRC patients with mutated KRAS, who showed aggravation even after 2 regimens with oxaliplatin and irinotecan. S-1 (80-120 mg/body) was administered for 4 weeks and withdrawn for 2 weeks. The dose of S-1 was decided according to the subjects’ body surface area. Bevacizumab (5 mg/kg) was administered on Days 1, 15, and 29. This treatment was provided until progression. The primary endpoint was disease control rate (DCR), and secondary endpoints were response rate (RR), median progression free survival (mPFS), overall survival (OS), and adverse event (AE). Results: A total of 31 subjects mutated KRAS were enrolled between August 2009 and July 2011. An independent review committee evaluated antitumor effects in eligible 29 of the 31 subjects in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST). Two subjects in whom antitumor effects could not be evaluated were excluded. The DCR was 69% (95% confidence interval [CI], 49.2-84.7%), RR 0% (95% CI, 0-12.3%), mPFS 3.7 months (95% CI, 2.7-6.5 months), OS 9.0 months (95% CI, 7.5-12.0 months), and the median observation period 9.0 months. In 30 subjects for safety evaluation, the incidence of Grade 3 or greater adverse events was 50%. There was no treatment-related death. Major adverse events were anorexia (Grade 3 or greater, 20%), diarrhea (Grade 3, 10%), and decreased hemoglobin (Grade 3 or greater, 16.7%). Conclusions: The results suggest that 3rd-line chemotherapy combined bevacizumab with S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS. Clinical trial information: NCT00974389.

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