Phase II trial of oxaliplatin and gemcitabine with bevacizumab in first-line advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17009-17009 ◽  
Author(s):  
E. Davila ◽  
R. Lilenbaum ◽  
L. Raez ◽  
L. Seigel ◽  
J. Tseng ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Bleeding Complications ◽  
Hematologic Toxicity ◽  
Ischemic Bowel ◽  
Prior Therapy ◽  
Stage Disease ◽  
Ecog Ps ◽  
Nsclc Patients

17009 Background: Oxaliplatin-Gemcitabine (GemOx) is an active and well tolerated. Bevacizumab (BV) prolongs survival when combined with carboplatin-paclitaxel. This phase II trial evaluates the efficacy of GemOx + BV as 1st line therapy for advanced NSCLC patients. Methods: Pts with stage IIIB (effusion) and IV non-squamous NSCLC, ECOG PS 0 or 1, no CNS metastasis, and no other contraindications to BV, are eligible. Prior therapy for earlier-stage disease allowed if completed at least 12 months before enrollment. Treatment consists of Gem 1000 mg/m2 on d1 and 8, Ox 130 mg/m2 on d1, and BV 15 mg/kg on d1, repeated every 3 wks for a total 4 cycles. Pts who respond or have stable disease receive BV maintenance until progression. Main endpoints are response rate (RR), grade (Gr) 3–4 toxicities, time to progression (TTP), and overall survival (OS). Results: As of 12/05, 26 out of 50 projected pts have been enrolled from 4 institutions. M/F 17/9; median age 65y (45,81); IIIB/IV 3/23; PS 0/1 8/18. Median F/U time is 3.7 months. 24 pts are evaluable for toxicity: 1Gr3 ANC; 1Gr3 and 4 PLT; no FN.3 Gr3 diarrhea and 2 Gr3 N/V; 1Gr3 and 4 hypophosphatemia; 1 pt had ischemic bowel after the 1st cycle, recovered fully and was removed from study; 1 pt died of liver failure in the 1st cycle. No bleeding complications have occurred. 22 pts are evaluable for RR (ITT): 7 PR (31%); 8 SD (36%). TTP and OS data not yet available. Conclusions: This is the first report of GemOx in combination with BV in advanced NSCLC. This regimen has minimal hematologic toxicity but selected non-hematologic toxicities are noted. Activity appears promising and merits further investigation. Accrual is ongoing. [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 trial of irinotecan, carboplatin, and bevacizumab in patients with limited-stage small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18133-18133 ◽  
Author(s):  
J. D. Zubkus ◽  
D. R. Spigel ◽  
F. A. Greco ◽  
D. A. Yardley ◽  
H. A. Burris ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Small Cell ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Ecog Ps

18133 Background: In a previously reported phase II trial bevacizumab (B) was used as maintenance therapy following induction with irinotecan (I), carboplatin (C) and radiotherapy (RT) in patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). 1-year progression- free survival (PFS) and overall survival (OS) were 53% and 70%, respectively. In the present multicenter community-based trial B is given with induction chemoradiotherapy and as maintenance therapy. Methods: The primary endpoint is to assess the median PFS. Eligibility criteria: newly diagnosed LS-SCLC, measurable disease, ECOG PS 0–1, and informed consent. Exclusion criteria: hemoptysis and therapeutic anticoagulation. Treatment: I 60mg/m2 IV D1, 8, 15, C AUC=4 IV D1, and B 10 mg/kg IV D1 and 15 every 28D. Pts received concurrent RT to 61.2 Gy starting with the 3rd cycle, and were restaged every 8 weeks. If no progressive disease (PD) or excessive toxicity after 4 cycles, pts received B x 6 months. Prophylactic cranial irradiation was used at M.D. discretion. This 2-stage trial was designed to achieve a 40% improvement in historical median PFS of 12–14 months. Results: 20 pts were enrolled from 4/06 to 12/06 (trial ongoing, n=50 planned). Data are available for 14 pts in this analysis. Baseline features: median age 64 years; male/female, 21%/79%; and ECOG PS 0/1, 64%/36%. The objective response rate was 78% (95% CI 45%-94%) - all partial responses. No pt had PD. 7 pts were not evaluable: too early, 5 pts; off study (toxic megacolon, 1 pt; intercurrent illness, 1 pt). With a median follow-up of 5 months, the median PFS has not been reached. Grade (G) 3/4 non-hematologic toxicity with induction occurring in more than 2 pts: diarrhea (29%) and esophagitis, fatigue, pain (21% each). G3/4 hematologic toxicity: leukopenia (21%), neutropenia (14%), and thrombocytopenia (43%). There have been 2 G3/4 bleeding events with induction: suspected tracheoesophageal fistula with death (possibly treatment-related), 1 pt; and hematochezia, unrelated, 1 pt. Conclusions: This trial continues to be closely monitored for safety. Further accrual and longer follow-up are necessary to assess if B can be safely combined with chemoradiotherapy and improve efficacy. No significant financial relationships to disclose.

A phase II trial of neoadjuvant dasatinib (Neo-D) in muscle-invasive urothelial carcinoma of the bladder (miUCB): Hoosier Oncology Group GU07-122 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4586-4586 ◽  
Author(s):  
Noah M. Hahn ◽  
Siamak Daneshmand ◽  
Edwin M. Posadas ◽  
Michael O. Koch ◽  
Richard Bihrle ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Tumor Tissue ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Post Treatment ◽  
Hematologic Toxicity ◽  
Biologic Activity ◽  
Grade 3 ◽  
Ecog Ps

4586 Background: Neoadjuvant chemotherapy (NC) preceding radical cystectomy (RC) is an accepted standard for miUCB patients (pts). Dasatinib (D) is an oral tyrosine kinase inhibitor of Src mediated signaling, and has demonstrated promising preclinical anti-tumor activity, providing a rationale to evaluate Neo-D in human miUCB. Methods: A phase II trial was conducted to assess the safety and biologic activity of Neo-D in miUCB. Key eligibility criteria included: miUCB (T2-T4a, N0, M0), unsuitable or willing to forego platinum-based NC, adequate TURBT tissue available, ECOG PS 0-1, creatinine < 2 x ULN. Pts received D 100 mg po once daily for 28 +/- 7 days followed by RC 8-24 hours after the last dose. The primary endpoint was feasibility defined as > 60% of pts completing therapy without treatment-related dose limiting toxicity (DLT) specified as grade 4 hematologic toxicity, grade 3 non-hematologic toxicity, or any grade 2 toxicity > 14 days. Secondary endpoints included the assessment of biologic activity as assessed by pre- and post-treatment tumor tissue immunohistochemistry analysis of Src, pSrc, EPHA2, pEPHA2, FAK, pFAK, AKT, pAKT, CD31, Ki67, TUNEL. Results: The study completed accrual with enrollment of 25pts. 22 and 24 pts were respectively evaluable for feasibility and toxicity endpoints. Patient demographics included: median age – 62, M/F – 20/5, ECOG PS 0/1 – 19/6. Baseline tumor staging included: T2 – 17, T3 – 7. The study achieved its primary endpoint with 15 pts (68%) completing therapy without treatment related DLT’s. DLT’s included: fatigue (2 pts), DVT/PE, abdominal pain, supraventricular tachycardia, enteric fistula, and hematuria (1 pt each). Frequency of highest observed toxicity on study included: Grade 1 – 13%, Grade 2 – 38%, Grade 3 – 46%, Grade 4 – 4%. Among 22 patients, pathologic stage at RC was T1/Tis in 3 pts (14%), ≥T2 in 19 pts (86%), and node positive in 6 pts (27%). Correlative analyses of pre- and post-treatment tumor Src signaling are ongoing and will be updated at the meeting. Conclusions: Neoadjuvant dasatinib preceding RC is feasible in miUCB patients. Tumor tissue correlative studies may provide directions for further development.

scholarly journals Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinghao Ai ◽  
Zhengbo Song ◽  
Hong Jian ◽  
Zhen Zhou ◽  
Zhiwei Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Growth Factor Receptor ◽  
Small Cell Lung ◽  
Open Label ◽  
Once Daily ◽  
Epidermal Growth ◽  
Exon 20 ◽  
Nsclc Patients

Abstract Background Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy. Methods This is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate. Discussion The addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds. Trial registration ClinicalTrials.gov Identifier: NCT04382300. Registered on May 11, 2020.

Phase I/II Study of Combination of Sorafenib, Vorinostat, and Bortezomib in Acute Myeloid Leukemia with FLT3-ITD Mutation or Monosomy 5, 7, or Complex Cytogenetics

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 976-976 ◽  
Author(s):  
Mohammad Abu Zaid ◽  
H. Scott Boswell ◽  
Larry D. Cripe ◽  
Yan Liu ◽  
Jill Weisenbach ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Hematologic Toxicity ◽  
Refractory Disease ◽  
Prior Therapy ◽  
Poor Risk ◽  
Common Grade ◽  
Heavily Pretreated ◽  
Ecog Ps

Abstract Introduction We report the phase I data from ongoing phase I/II study of combination of targeted agents sorafenib, vorinostat and bortezomib in poor-risk AML. Our findings from a previous phase I study, performed at Indiana University, of the combination of sorafenib and vorinostat in patients with AML suggested that two major groups of patients may benefit most from this targeted regimen, patients with FLT3-ITD mutation, and those with complex or poor-risk cytogenetics (monosomy 5 or 7). In addition, our findings were suggestive of a synergistic action obtained by inhibition of p52NFKB, a down-stream target of proteosome inhibition. With the hypothesis that addition of proteasome inhibitor bortezomib would be of benefit towards such synergism, a phase I/II clinical trial combining bortezomib with sorafenib and vorinostat was initiated. The phase I data is reported here. Methods The phase I portion of the trial utilized a traditional 3+3 design on five cohorts to determine the MTD of the combination. Eligibility required age ≥18, a confirmed baseline diagnosis of AML by the revised guidelines of the International Working Group for AML, and included untreated disease in elderly or relapsed/refractory disease in all ages, monosomy 5,7 or complex cytogenetics or positive FLT3-ITD mutation, ECOG PS 0-2, and adequate kidney and liver function. Dose limiting non-hematologic toxicity was defined per the CTCAE v4.0 criteria. Hematologic toxicity was prolonged cytopenia with <5% cellularity and no evidence of leukemia in the bone marrow lasting >42 days after discontinuation of therapy. The treatment was given in cycles, with each cycle consisting of 2 weeks treatment followed by 1 week off. Dose and/or administration schedule of drugs were escalated between the cohorts. Results Seventeen patients were enrolled on the phase I portion. Fifteen patients completed at least one cycle of treatment and 2 were taken off earlier due to disease progression. The median age was 51 years (24-73), and 10 (59%) patients were male. Sixteen patients had prior therapy at time of enrollment and 59% were heavily pretreated (≥3 lines of therapy) including stem cell transplantation in 29%. Fifty nine percent had FLT3-ITD mutation and 53% had poor-risk cytogenetics. No DLTs were seen in all 5 cohorts and MTD was not reached. The safe dose for phase II was determined at sorafenib 400 mg bid, vorinostat 200 mg bid (both for 14 days), and bortezomib 1.3 mg/m2IV on days 1,4,8,11, every 21 days. Most common grade 1-2 toxicities were diarrhea (59%), nausea (41%), vomiting (24%) and rash (18%). Majority of toxicities were grade 1. Response was observed in 6 patients (40%) with 4 achieving a complete remission (27%). All responders had relapse/refractory disease. Conclusion The combination of sorafenib, vorinostat, and bortezomib when given with a 2-week on, 1-week off schedule is safe with minimal side effects, and tolerable as an outpatient regimen for the treatment of poor-risk AML. Encouraging responses with this regimen are seen in these patients. The phase II portion of the study is currently ongoing. Correlative studies to further elucidate the molecular attributes of efficacy of this regimen in poor-risk AML are underway. Updated results will be presented. Disclosures No relevant conflicts of interest to declare.

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