Phase II randomized trial of docetaxel plus cetuximab or bortezomib in patients with advanced NSCLC and performance status (PS) 2—CALGB 30402

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
R. Lilenbaum ◽  
X. Wang ◽  
L. Gu ◽  
J. Kirshner ◽  
E. Vokes
Keyword(s):  
Phase Ii ◽  
Type I Error ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Type I ◽  
Weekly Schedule ◽  
Male Response

7595 Background: There is no standard treatment for patients (pts) with advanced NSCLC and PS 2. Docetaxel (D) is active and well tolerated on a weekly schedule. Cetuximab (C) and Bortezomib (B) are new agents with activity in NSCLC. We explored these two new combinations in PS 2 pts. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to D 30 mg/m2 d1,8,15 q. 28 days in combination with either C 400 mg/m2 week 1 then 250 mg/m2 weekly, or B 1.6 mg/m2 d1,8,15 q. 28 days for 4 cycles. Pts with CR/PR/SD were allowed to continue C or B until PD. The study was non-comparative and the primary endpoint was progression-free survival (PFS) rate at 6 months. The trial had a type I error of 0.0746 and power of 0.9 to differentiate a 6-mo PFS of <20% vs. >42%. Results: 64 pts were enrolled between 7/05 and 9/06. 5 were ineligible and 3 never received protocol treatment. Results are reported for 55 pts (27 D+C; 28 D+B). Most pts had stage IV adenoCa and 13% had brain metastases. Median age was 70 (range, 35–88) and 65% were male. Response: 10.5% for D+C and 13.6% for D+B. Median PFS was 3.1 mo for D+C and 1.8 mo for D+B. PFS rates at 4 mo (data not yet mature for 6-mo): 33% and 28%, respectively. Median survival: 3.8 mo for D+C and 3.3 mo for D+B. Gr 3/4 hematologic toxicity was 17% in both arms. Gr 3/4 non-heme toxicities were 44% in D+C and 36% in D+B arm. 5 pts died of treatment-related toxicities (3 D+C; 2 D+B). Conclusions: These results confirm the poor prognosis associated with a PS of 2. Based on our preliminary analysis, neither combination produced results that justify further research in this subset of patients. The treatment of PS 2 patients with advanced NSCLC remains a vexing problem and new approaches are urgently needed. No significant financial relationships to disclose.

A randomized, multicenter, phase II trial of gemcitabine (G), cisplatin (C) +/- veliparib (V) in patients with pancreas adenocarcinoma (PDAC) and a known germline (g)BRCA/ PALB2 mutation.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 639-639 ◽  
Author(s):  
Eileen Mary O'Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Hematologic Toxicity ◽  
Type I ◽  
Exact Test ◽  
Entire Cohort

639 Background: gBRCA 1,2 mutations occur in 5-8% PDAC. Platinum and poly-ADP ribose polymerase inhibitors (PARPi) effective in BRCA-mut cancers. Phase I GC + V high RR 78%; combination may delay resistance in PDAC (O’Reilly, Cancer, 2018). Herein, we evaluate GC +/- V in a multi-national, randomized phase II trial. Methods: Eligibility: Untreated germline (g)BRCA, PALB2 mut PDAC; measurable stage III/IV; ECOG 0-1. Randomized 1:1 Arm A or B. Treatment: Arm A: G 600 mg/m2 IV, C 25 mg/m2 IV, d3 and 10, V 80 mg PO BID day 1-12, all q 3 weeks or Arm B: GC only. Primary endpoint: RECIST 1.1 response rate (RR). Simon 2-stage per arm: null hypothesis 10% vs promising 28%; type I, II error 10%. Secondary endpoints: progression-free survival (PFS), OS (m), disease control rate (CR+PR+SD), safety and correlative analyses. PFS, OS compared between arms using log-rank test and RR, DCR using Fisher’s exact test between arms. Results: N = 52 enrolled 01/14- 11/18. N = 2 withdrew Arm B. N = 50 for ITT. Male = 22 (44%), Female = 28. Median age = 64 years (range 37-82). BRCA1 N = 12, BRCA2 N = 35, PALB2 N = 3. Stage III N = 8; Stage IV N = 42. Hematologic Toxicity: Arm A vs Arm B: Gd 3-4 neutropenia 13 (48%) vs 7 (30%); Gd 3-4 platelets 15 (55%) vs 2 (9%); Gd 3-4 anemia 14 (52%) vs 8 (35%). Non-hematologic toxicity similar Arm A vs B. Exploratory analyses (combined Arms): Med OS if > 4 m platinum → PARPi: 23 m (95%CI 6.5- 53.9). Med OS by BRCA: BRCA1: 14 m (8.1- 18.5); BRCA2: 20.2 m (12.3- 24.4). Med OS by ECOG: ECOG 0: 23 m (13.8- 24.5); ECOG 1: 14.3 (8.1 vs 16.4). Two-year OS rate for entire cohort: 30.6% and 3-year OS: 17.8%. Conclusions: GC +/- V very active in gBRCA/PALB2 mut PDAC with high RR, PFS, OS with both A, B significantly exceeding threshold RR. Improved DCR arm A vs B, but with greater heme toxicity A vs B. Study confirms GC as reference treatment in gBRCA/PALB2 with durable survival in subset. Funding: National Cancer Institute, CTEP, Lustgarten Foundation, AbbVie. Clinical trial information: NCT01585805 . [Table: see text]

Phase II trial of atezolizumab (A) + carboplatin (C) + pemetrexed (P) + bevacizumab (B) in pts with stage IV non-squamous non-small cell lung cancer (NSq-NSCLC): Big Ten Cancer Research Consortium Study LUN 17-139.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9034-9034
Author(s):  
Fatemeh Ardeshir-Larijani ◽  
Sandra K. Althouse ◽  
Ticiana Leal ◽  
Lawrence Eric Feldman ◽  
Taher Abu Hejleh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Febrile Neutropenia ◽  
Phase Ii ◽  
Type I Error ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Colonic Perforation ◽  
Type I ◽  
Big Ten ◽  
Research Consortium

9034 Background: The addition of A to C+ Paclitaxel (Pac) + plus B improved progression free survival (PFS) and overall survival (OS) compared with C + Pac + B alone in pts with metastatic NS-NSCLC. However, C + Pem is more commonly used for this patient population with a shorter infusion time and favorable toxicity profile compared with Pac. Methods: Multicenter single arm phase II clinical trial of chemo and immunotherapy-naïve pts with stage IV NSq-NSCLC. All pts received A (1200 mg, D1) + C (AUC 5, D1) + P (500 mg/m2, D1) + B (15mg/kg D1) q3 week x4. If non-PD, pts could receive maintenance APB until PD or intolerable side effects. The primary endpoint was 1 yr. PFS. Sample size of 42 planned with 87% power and two-sided type I error of 0.05 for 1 yr PFS. Secondary endpoints included ORR, disease control rate (DCR) [defined by CR + PR + SD], and toxicity. Results: 30 pts were enrolled from 11/15/2018 to 10/5/2020. The study was closed early due to 3 patient deaths, possibly related to treatment (VTE, Febrile neutropenia, colonic perforation). Median age 64 (range 38-83); M/F 20/10; mutations in EGFR/ALK/KRAS/BRAF (5/1/4/2); PD-L1 TPS < 1%/1-49%/ > 50% (9/14/6) and one pt did not have PDL-1 status. Median f/u was11.6 mos (range 1-20). ORR 35.71% (95% CI: 18.64%-55.95%), DCR 92.85% (95% CI: 83%-100%). 1yr PFS and OS were 55.27% and 82.90% respectively. The most common G III and G II toxicity were HTN (20%) and fatigue (33.3%).3 pts had G IV toxicity (Anemia, Febrile neutropenia and colonic perforation) and 2 pts had Grade (G) V toxicity (VTE, Hypoxia/Sepsis). Conclusions: Atezolizumab + Carboplatin + Pemetrexed + Bevacizumab was associated with longer DCR, PFS, and OS than historical controls. 3 on-treatment deaths, possibly related to therapy (more likely bevacizumab), prompted early closure. A phase 3 study evaluating this regimen is ongoing by another group NCT03786692. Clinical trial information: NCT03713944.

Randomized, double-blind, placebo-controlled phase II study of carboplatin and paclitaxel with or without vorinostat, a histone deacetylase inhibitor (HDAC), for first-line therapy of advanced non-small cell lung cancer (NCI 7863)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
S. S. Ramalingam ◽  
M. Maitland ◽  
P. Frankel ◽  
A. E. Argiris ◽  
M. Koczywas ◽  
...  
Keyword(s):  
Phase Ii ◽  
Type I Error ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Hepatic Function ◽  
Placebo Treatment ◽  
Type I ◽  
Double Blind

8004 Background: Vorinostat, a HDAC inhibitor, enhances paclitaxel and platinum-mediated anti-cancer activity in preclinical studies by enhanced tubulin acetylation and DNA fragmentation respectively. Promising activity with carboplatin (C), paclitaxel (P), and vorinostat in patients with advanced NSCLC in the phase I study (Ramalingam et al, Clin Cancer Res, 2007) prompted this placebo-controlled, randomized phase II study. Methods: Pts. with stage IIIB (wet) or IV NSCLC, performance status (PS) 0/1, no prior therapy and adequate bone marrow, renal and hepatic function were randomized (2:1) for therapy with PC with either vorinostat or placebo. Treatment consisted of C: AUC=6 mg/ml.min; and P 200 mg/m2 both given on day 3 along with either vorinostat (400 mg PO QD) or placebo on days 1–14 of each 3 wk cycle to a maximum of 6 cycles. The estimated sample size to demonstrate a 50% improvement in response rate for vorinostat over placebo was 93 pts. (one-sided P, type I error 10%). Results: Ninety-four pts. were enrolled (vorinostat-64; placebo-32). Pts. baseline characteristics were similar between the two arms (median age 64, male 60%, PS 0 40%, brain mets 16%). Median # cycles: vorinostat-3.5; placebo - 4. The confirmed response rate was superior with vorinostat over placebo (34% vs. 12.5%, P = 0.02). At the time of analysis, the preliminary median PFS for vorinostat and placebo were 5.75 and 4.1 m respectively (ITT). Follow up for survival is ongoing. Common grade 3/4 toxicities (vorinostat vs. placebo): neutropenia (44% vs. 47%); thrombocytopenia (33% vs. 16%); fatigue (13% vs. 3%); hyponatremia (21% vs. 6%); diarrhea (5% vs. 0). Discontinuation from study after cycle 1 was higher with vorinostat (27% vs. 16%). Biomarker studies on baseline tumor tissue and peripheral blood cells are ongoing. Conclusions: Administration of vorinostat with carboplatin and paclitaxel resulted in a significantly superior response rate for pts.with advanced NSCLC. HDAC inhibition is a novel therapeutic strategy for treatment of NSCLC. Supported by ASCO Career Development Award to S.S.Ramalingam, and NCI NO1-CM-62209, NO1-CM-62201, NO1-CM-62208. [Table: see text]

Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial

2022 ◽  
Author(s):  
Matthew A. Powell ◽  
Virginia L. Filiaci ◽  
Martee L. Hensley ◽  
Helen Q. Huang ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Type I Error ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Type I ◽  
Primary Analysis ◽  
Free Survival ◽  
Oncology Trial ◽  
Limited Precision

PURPOSE This phase III randomized trial ( NCT00954174 ) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS). PATIENTS AND METHODS Adults with chemotherapy-naïve UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test. RESULTS The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; P < .01 for noninferiority, P > .1 for superiority). The median progression-free survival was 16 versus 12 months (HR = 0.73; P = < 0.01 for noninferiority, P < .01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant. CONCLUSION PC was not inferior to the active regimen PI and should be standard treatment for UCS.

Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8560-8560 ◽  
Author(s):  
D. G. Perez ◽  
V. Suman ◽  
T. Amatruda ◽  
M. Gornet ◽  
R. Morton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Unresectable Stage ◽  
Full Study ◽  
Grade 3 ◽  
Endothelial Growth Factor ◽  
Stage Iv Melanoma

8560 Background: In patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets vascular endothelial growth factor (VEGF) might be able to control tumor growth and progression much more effectively than chemotherapy alone. Methods: A two-stage phase II clinical trial was conducted in patients with unresectable stage IV melanoma to assess the anti-tumor activity and toxicity profile of the combination of paclitaxel (80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle), carboplatin (AUC = 6 IV on day 1) and bevacizumab (10 mg/kg IV on days 1 and 15). The primary end point of the study was the 8-week progression-free survival rate (PFS). Enrollment to the second stage of the study was opened if 8 or more of the first 20 patients enrolled remained progression-free at 8 weeks. Eligible patients had measurable disease by RECIST criteria, a performance status (PS) of 0–2 and acceptable pre-registration organ function. Exclusion criteria included: brain metastases, significant recent bleeding, uncontrolled hypertension and ongoing anticoagulation. The study opened in February 2006 and completed full study accrual in August 2006. Data from the 20 patients enrolled in the first stage are presented here. Results: Patients (60% male) had a median age of 63 and had a good performance status (85% had PS of 0). M1c disease was present in 45% of patients and 35% had undergone previous chemotherapy for stage IV melanoma (50% prior immunotherapy). Only 6 patients did not complete more than 2 cycles of chemotherapy due to refusal (3), desire for alternative treatment (1) or progression (2). Median follow-up among the 15 patients still alive was 5.5 months (range: 6 weeks - 9 months). The 8-week PFS rate was 70% (14/20). The median time to progression was 163 days. One partial response was observed. There were 3 disease-related deaths at 65, 120 and 190 days post-registration. The most common toxicities were neutropenia (95%; 45% = grade 3), anemia (95%; 15% = grade 3), fatigue (90%; 5% = grade 3), leukopenia (85%; 25% = grade 3), and thrombocytopenia (75%; 5% = grade 3). Conclusions: The combination of paclitaxel, carboplatin and bevacizumab appears to be well tolerated and clinically active in patients with stage IV melanoma. No significant financial relationships to disclose.

Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19062-e19062
Author(s):  
J. R. Fischer ◽  
F. Griesinger ◽  
T. Fink ◽  
E. Buchholz ◽  
T. Salm ◽  
...  
Keyword(s):  
Phase Ii ◽  
Partial Remission ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Benefit Risk Assessment

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]

Final report of an open-label phase II trial of bevacizumab plus docetaxel and gemcitabine in metastatic, previously untreated nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18046-e18046
Author(s):  
Nathan A. Pennell ◽  
Sujith R. Kalmadi ◽  
Marc A. Shapiro ◽  
Hamed Daw ◽  
Cristina P. Rodriguez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Final Report ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Open Label Phase

e18046 Background: Platinum and non-platinum doublet chemotherapy has similar efficacy in advanced NSCLC patients (pts). Bevacizumab (B) improves outcomes when added to platinum doublets, but its safety and efficacy in combination with non-platinum doublets is unknown. This study was designed to test the combination of B, docetaxel (D), and gemcitabine (G) in first-line treatment of advanced NSCLC. Methods: Pts with metastatic, non-squamous NSCLC, PS 0-1, and measurable disease by RECIST were enrolled in this open-label, single arm phase II trial. Pts received D (75 mg/m2) on d1, G (900 mg/m2) on d1 & 8, and B (15 mg/kg) on d1 every 21d for up to 6 cycles, followed by B maintenance until progression or 12 mos total. Pts received growth factor d9. CT scans were performed every 6 wks. The primary endpoint was 1-yr progression-free survival (PFS), with secondary endpoints of safety, objective response rate (ORR), overall PFS, and overall survival (OS). Pts with tumor cavitation, untreated brain metastases, and hemoptysis were excluded. Planned enrollment was 46. Results: 13 pts were enrolled from 12/2009 to 4/2011. Pt characteristics: Median age 63 (35-69), 85% male, PS 0 (38%), PS 1 (62%). The median # of cycles of chemotherapy was 6 (1-6), median # cycles of B was 4 (1-15), with 2 pts coming off study prior to the first evaluation (1 grade 5 encephalopathy, 1 grade 4 febrile neutropenia). 5 pts (38%) had chemo dose reduction and 4 (31%) discontinued treatment for toxicity. 3 pts (23%) discontinued B prior to progression, 2 for tumor cavitation and 1 for grade 1 hemoptysis. The grade 3-5 non-hematologic toxicity rate was 69%, with 6 pts (46%) hospitalized with pneumonitis/pneumonia felt possibly related to study drugs. At this point enrollment was halted for safety concerns. The 1-yr PFS was 8%, and the median PFS was 6.9 mos (95% CI 2.0-NYR). 11 pts were evaluable for response, and 6 pts had partial responses for an ORR of 55%. The median OS was NYR with median follow up of 10.9 mos. Conclusions: The combination of B, D, and G was not tolerable at the doses and schedule used in this study. A formal phase I trial is needed if this combination is to be investigated further.

Phase II clinical trial of intravesical bacillus Calmette-Guerin (BCG) followed by sunitinib for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 293-293 ◽  
Author(s):  
Alexander M. Helfand ◽  
Cheryl T. Lee ◽  
Khaled Hafez ◽  
Maha Hussain ◽  
Monica Liebert ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Type I Error ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Complete Response ◽  
Type I ◽  
Incomplete Response ◽  
Hand Foot Syndrome

293 Background: We conducted a phase II trial to evaluate combination therapy with intravesical BCG + sunitinib for prevention of recurrence and progression of NMIBC. Methods: Patients with high-grade clinical ≤ T1N0M0 NMIBC without BCG in the past year were eligible and received induction BCG followed 2 weeks later by 28 days of sunitinib (50mg). The primary endpoint was 3 month complete response (CR) by biopsy and cytology. Patients with incomplete response were eligible for a second cycle of BCG + sunitinib. Secondary endpoints included 2-year recurrence and progression-free survival (RFS, PFS). Toxicity was graded according to the NCI CTCAE v.3.0. The Simon Minimax 2-stage study had 80% power with a 5% type I error assuming a 3m CR of 75% with sunitinib + BCG compared to 55% with BCG alone. If ≥ 25/36 evaluable patients achieved a 3m CR, then the treatment would be considered for further study. Binomial proportions, confidence intervals and Kaplan-Meier estimates are reported. Results: Of 36 evaluable patients, median age was 65.9 years (IQR 59-72). Initial stage was T1 (19), Ta (9), and CIS (8). Thirty-six percent completed sunitinib without interruption. Treatment was delayed (median 12 days (IQR 9-16)) and dose was reduced to 37.5 mg in 13 patients. One patient had reduction to 25mg with re-escalation to 37.5mg. One patient completed a 2nd cycle of BCG + sunitinib for incomplete response. BCG maintenance therapy was given to 21 patients. Of 133 adverse events in 34/36 patients, 6 (4.5%) in 5 patients were ≥ grade 3: thrombocytopenia, diarrhea (2), shingles, extremity rash/pain and hand + foot syndrome. CR at 3m included 26/36 (72%, 95% CI[55,86]) reaching the primary endpoint. The patient who completed a 2nd cycle of BCG induction and sunitinib had CR at 6 months. 2y RFS (patients with intact bladder) was 77% (95% CI[58,88]) and 2y PFS was 100%. Conclusions: The primary endpoint of the study of 25 3m CR has been reached. Combined treatment with BCG + sunitinib is associated with low rates of recurrence and progression. Adverse effects were common and frequent but few were serious. BCG + sunitinib may produce outcomes superior to BCG alone. (Study supported by Pfizer, Inc) Clinical trial information: NCT00794950.

Randomized, double-blind, placebo-controlled, phase II trial of first-line platinum/docetaxel with or without erlotinib (E) in patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCCs).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6017-6017 ◽  
Author(s):  
William Nassib William ◽  
Lei Feng ◽  
Merrill S. Kies ◽  
Salmaan Ahmed ◽  
George R. Blumenschein ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Type I Error ◽  
Performance Status ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Type I ◽  
Phase 2 ◽  
First Line ◽  
Double Blind ◽  
Phase 2 Trial

6017 Background: In a single-arm, phase 2 study, we previously demonstrated that in pts with R/M HNSCC, cisplatin, docetaxel and E improved progression-free survival (PFS) compared to historical data (Kim et al., ASCO 2006). Herein, we evaluated this regimen in a single center, randomized, phase 2 trial. Methods: Pts with R/M HNSCC, with a performance status (PS) 0-2, were randomized (1:1) to receive up to 6 cycles of first-line chemotherapy with cisplatin 75 mg/m2 (or carboplatin AUC 6) and docetaxel 75 mg/m2 i.v. on day 1 every 21 days, plus placebo (P) vs. E 150 mg p.o. daily, followed by maintenance P or E until disease progression. The primary endpoint was PFS. With 120 pts, the study had 80% power to detect an improvement in median PFS from 3.0 to 4.9 months with a two-sided type I error rate of 0.1. Results: From 05/2010 to 07/2015, 120 pts were randomized to the P (N = 60) or E (N = 60) groups. All pts but one initiated treatment and were eligible for evaluation of the primary endpoint – 92 males; median age 62 years; 52 oropharynx, 40 oral cavity, 19 larynx, 8 hypopharynx cancer pts; 86 current/former smokers; 43 with recurrence within 6 months of completion of local treatment; 27 with prior exposure to EGFR inhibitors. Median PFS was 4.4 vs. 6.1 months for the P and E groups, respectively (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.42-0.95 months, p = 0.026). Response rates were 44% vs. 56% for P vs. E (p = 0.21). Median overall survival (OS) for P- and E-treated pts was 13.7 vs. 17.0 months (HR = 0.67, 95% CI 0.43-1.04, p = 0.07). Benefits from E on PFS and OS were more pronounced in pts with oropharyngeal tumors (p≤0.05 for interaction). In the E group, first-cycle rash grade 2-4 (34% pts) was associated with longer OS (HR = 0.40, p = 0.02). E-treated pts experienced a higher incidence of grade 3-4 adverse events (33.9 vs. 53.3%), including diarrhea (3 vs.17%), dehydration (5 vs. 15%), nausea (5 vs. 14%), rash (0 vs. 12%). Conclusions: This study met its primary endpoint. Addition of E to first-line platinum/docetaxel improved PFS and OS. This regimen may warrant further evaluation in randomized, phase 3 trials. Clinical trial information: NCT01064479.

A randomized, phase II efficacy assessment of multiple MET kinase inhibitors in metastatic papillary renal carcinoma (PRCC): SWOG S1500.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4599-TPS4599 ◽  
Author(s):  
Sumanta K. Pal ◽  
Catherine M. Tangen ◽  
Ian Murchie Thompson ◽  
Brian M. Shuch ◽  
Naomi B. Haas ◽  
...  
Keyword(s):  
Phase Ii ◽  
Metastatic Disease ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Performance Status ◽  
Progression Free Survival ◽  
Type I ◽  
Type Ii ◽  
Randomized Phase Ii ◽  
Clear Cell Rcc

TPS4599 Background: PRCC constitutes approximately 15% of RCC cases, and no standard of care exists for metastatic disease. Approved VEGF- and mTOR-directed therapies for clear cell RCC in metastatic PRCC (mPRCC) have generally been ineffective. Trials assessing sunitinib and everolimus in non-clear cell RCC show a numerical advantage in progression-free survival (PFS) with sunitinib therapy. Prospective studies evaluating sunitinib in mPRCC show a broad range of efficacy, with PFS ranging from 1.6-6.6 months. Another possible approach to treating mPRCC is to target the MET protooncogene, which is frequently altered across both type I and type II disease. SWOG 1500 is a randomized, phase II study which will compare sunitinib to three MET-directed therapies in pts with mPRCC. Methods: Eligible pts will have PRCC (type I, type II or NOS), Zubrod performance status 0-1, and measurable metastatic disease. Pts may have received up to 1 prior systemic therapy, with the exception of prior VEGF-directed treatments. Treated brain metastases are allowed. Tissue must be available for central pathologic review of papillary subtype. Pts will receive either oral sunitinib, cabozantinib, crizotinib or savolitinib in a 1:1:1:1 randomization, with stratification by (1) prior therapy (0 vs 1) and (2) PRCC subtype (type I vs type II vs NOS). The primary endpoint of the study is to compare PFS with sunitinib to PFS with MET-directed therapies. Secondary endpoints in the study include comparison of response rate, overall survival and safety profile. Translational aims of the study include correlation of clinical outcome with MET mutation, copy number and other markers of MET signaling. Radiographic assessment will be performed every 12 wks. Interim analyses are planned for each arm. A total of 275 pts will be enrolled, with 26 pts registered as of Jan 30, 2017. Clinical trial information: NCT02761057.

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