A single-arm phase II trial to evaluate the combination of cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction chemotherapy (IC) in patients (pts) with unresectable SCCHN

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
R. Mesia ◽  
S. Vázquez ◽  
J. J. Grau ◽  
J. A. García-Sáenz ◽  
C. Bayona ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Stage Iv ◽  
Stage Design ◽  
Concomitant Boost ◽  
Secondary Neoplasm ◽  
Grade 3 ◽  
Ecog Ps

6015 Background: TPF combination is the new standard IC. Adding cetuximab to PF chemotherapy is superior to PF alone in metastatic disease. We incorporated cetuximab into IC with TPF and subsequent radiotherapy (RT) in unresectable SCCHN. Methods: Phase II trial conducted in 7 Spanish hospitals. Previously untreated pts aged 18–70 yrs, ECOG PS 0–1 with unresectable SCCHN were eligible. Induction comprised T 75mg/m2 day 1, P 75mg/m2 day 1, F 750mg/m2 days 1–5, and cetuximab 250mg/m2 days 1, 8, and 15 (initial dose 400mg/m2 on cycle (C) 1, day 1), repeated every 21 days x 4 C, with prophylactic antibiotics and G-CSF support. Subsequently, pts received accelerated RT with a concomitant boost (69.9Gy) and cetuximab 250mg/m2 weekly. The primary endpoint was the objective response rate (RR) to cetuximab TPF as neoadjuvant therapy. Simon's optimal two-stage design was used to calculate the sample size of 49 evaluable pts. Results: 50 pts were enrolled: median age 54 yrs (33–68); 44 male; all stage IV (T4=31, N2–3=40). Primary sites were: oropharynx, 23; hypopharynx, 16; oral cavity, 5; larynx, 4.41(82%) pts received all 4 cycles of cetuximab TPF; 47 pts received ≥2 C and were evaluable for response using RECIST. 3 pts received <2 C (2 deaths from intercurrent disease and febrile neutropenia, 1 secondary neoplasm diagnosed). The table shows RR. Serious grade 3/4 adverse events (AEs) were: neutropenia 24%; neutropenic fever 20%; infection 6%; thrombocytopenia 4%; diarrhea 12%; hepatotoxicity 4%; hypomagnesemia 2%. Grade 3 AEs were: nausea/vomiting 2%; mucositis 6%; renal failure 4%; asthenia 4%; rash 4%; hypotension 4%. There were 2 AE-related deaths (febrile neutropenia and hepatic insufficiency). Conclusions: The addition of cetuximab to TPF IC in pts with unresectable SCCHN yields a high RR, mainly CR, potentially prolonging survival. Cetuximab TPF combination should be given to pts with good PS with specialized support provided. [Table: see text] [Table: see text]

A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

Phase II trial of carboplatin in the management of malignant mesothelioma.

1990 ◽  
Vol 8 (1) ◽  
pp. 151-154 ◽  
Author(s):  
D Raghavan ◽  
P Gianoutsos ◽  
J Bishop ◽  
J Lee ◽  
I Young ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Trial ◽  
Objective Response ◽  
World Health ◽  
Hematological Toxicity ◽  
Who Grade ◽  
Life Threatening ◽  
Grade 3 ◽  
Health Organization

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

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]

Irinotecan plus temozolomide in children with recurrent or refractory neuroblastoma: A phase II Children's Oncology Group study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10011-10011
Author(s):  
R. Bagatell ◽  
L. M. Wagner ◽  
S. L. Cohn ◽  
J. M. Maris ◽  
C. P. Reynolds ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Bone Marrow Aspirate ◽  
Response Rate ◽  
Objective Response ◽  
Response Assessment ◽  
Stage Design ◽  
Combination Methods ◽  
Grade 3 ◽  
Experienced Grade

10011 Background: Treatment of children with relapsed or refractory neuroblastoma (NB) remains a challenge. Responses to irinotecan (IRN) + temozolomide (TEM) were seen in NB xenograft-bearing mice, and objective responses were observed in patients with NB treated on a phase I study of this combination. Methods: A phase II study of IRN (10 mg/m2/dose IV daily × 5 days times; 2 weeks) + TEM (100 mg/m2/dose PO daily × 5 days) for children with relapsed or refractory NB was conducted. A one-stage design (endpoint: best overall response) required 5 or more responders out of the first 25 evaluable patients on each of two strata: 1) patients with disease measurable by CT or MRI; and 2) patients with disease detected only by bone marrow aspirate/biopsy and/or MIBG scan. Patients with stable disease or better after 3 cycles could receive an additional 3 cycles of study therapy. International Neuroblastoma Response Criteria were used for response assessment. Radiographic responses were centrally reviewed. Results: Fifty-five eligible and evaluable patients were enrolled, 28 on stratum 1 and 27 on stratum 2. Four responses were observed in the first 25 evaluable stratum 1 patients, and five responses were observed in the first 25 evaluable stratum 2 patients. Three patients had complete responses, but the overall objective response rate (CR+PR) was 16% (9/55). Eleven (stratum 1) and 13 (stratum 2) patients had stable disease. Less than 5% of patients experienced Grade 3 or 4 diarrhea. Although 18% of patients on stratum 1 and 35% of patients on stratum 2 experienced Grade 3 or 4 neutropenia during the first 3 cycles of therapy, <10% of all patients developed evidence of infection while neutropenic. Thrombocytopenia (Grade 3 or 4) was observed in only 7% of patients on stratum 1 and 12% on stratum 2. Conclusions: The combination of IRN+TEM was well tolerated in patients with recurrent or refractory NB. There were 9 objective responses, including 3 complete responses. The minimum desired response rate was attained within stratum 2, but not stratum 1. IRN+TEM may be an appropriate backbone for further study in the relapse setting in combination with novel, targeted agents. No significant financial relationships to disclose.

A randomized phase II trial comparing two doses of lenalidomide for the treatment of stage IV ocular melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20012-e20012 ◽  
Author(s):  
J. B. Zeldis ◽  
C. Heller ◽  
G. Seidel ◽  
N. Yuldasheva ◽  
D. Stirling ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Ocular Melanoma ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Animal Data ◽  
Disease Stabilization ◽  
Grade 3

e20012 Background: Ocular melanoma is the most common primary intraocular malignancy in adults with an incidence of 4.3 new cases per million. Approximately 50% of patients will develop metastases and the mean survival of those with liver metastases is 8–10 months. There are no effective systemic therapies. Pre-clinical studies of the antiangiogenic and immunomodulatory agent, lenalidomide, have shown promise in animal models of human ocular melanoma. We therefore conducted a phase II trial comparing two doses of oral lenalidomide. Methods: Patients with stage IV ocular melanoma, who met eligibility criteria and demonstrated disease progression, were enrolled on an IRB approved prospective random assignment trial comparing 5 mg and 25 mg of lenalidomide administered once a day orally for 21 days with a 7 day recovery (one cycle). Lesions were measured at baseline and every 3 months and scored for response by RECIST criteria. Patients who completed 3 cycles were eligible for response evaluation. Patients with responding lesions or with stable disease could continue receiving the agent. Toxicity was assessed using the NCI Common Toxicity Criteria. Results: Seventeen patients (13 female, 4 male; mean age 53) met eligibility criteria and were randomized to 5 mg (9 patients) or 25 mg (8 patients) of lenalidomide. The agent was well tolerated at both doses with only three grade 3 toxicities (two decreased ANC and one rash/puritis) requiring dose adjustments. Sixteen patients were eligible for response assessments. Nine patients had progressive disease by RECIST criteria following 3 cycles of therapy. Seven patients (44%) had stable disease for a mean of 7 months (range 6–12 months). There were no RECIST defined responders. There were no differences between the two dose groups with respect to toxicity or disease stabilization. Conclusions: Lenalidomide is well tolerated at doses of 5 mg and 25 mg orally for a 21 day cycle by patients with stage IV ocular melanoma. While no responses were seen, disease stabilization for a mean of 7 months was seen in 44% of patients. This effect was consistent with the pre-clinical animal data. Based on these results, further development of lenalidomide in combination with other agents should be considered for the treatment of metastatic ocular melanoma. [Table: see text]

Survival analysis of induction cisplatin (CDDP)-docetaxel (DOC)-bevacizumab (BEV) chemotherapy followed by maintenance BEV-pemetrexed (PEM) therapy in advanced nonsquamous non-small cell lung cancer (NonSq NSCLC): A phase II trial from Okayama Lung Cancer Study Group 0903.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19040-e19040
Author(s):  
Naoyuki Nogami ◽  
Katsuyuki Hotta ◽  
Toshiyuki Kozuki ◽  
Hiroshige Yoshioka ◽  
Akihiro Nishiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Stage Iv ◽  
Induction Phase ◽  
Lung Cancer Study Group ◽  
Platinum Based Chemotherapy

e19040 Background: BEV maintenance therapy and PEM maintenance therapy in platinum-based chemotherapy yield a significant survival advantage in CALGB and PARAMUNT trials, respectively, but each agent gave only modest impact on survival. We conducted a phase II trial of CDDP-DOC-BEV therapy followed by maintenance BEV-PEM therapy inchemo-naïve advanced NonSq NSCLC. Methods: Forty-one patients (pts) participated in the induction phase, specified as four cycles of induction CDDP (80 mg/m2), DOC (60 mg/m2) and BEV (15 mg/kg) on day 1 of a 21-day cycle. Pts who had not progressed during CDDP-DOC-BEV received maintenance BEV (15 mg/kg) and PEM (500 mg/m2) on day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS, and the secondary endpoints included OS, toxicity, and response. Survival time was calculated from the date of registration. Results: Pt characteristics were as follows: median age: 62 yrs; 76% male; 32% PS 0; 73% stage IV; 93% Ad; 5% EGFR-mutant and 2% ALK-mutant. At the time of this analysis, 34 pts (83%) discontinued the treatment, mainly due to progressive disease (53%). The principal toxicity was myelosuppression (gr. 4 hematological: 21 pts [51%]), and grs. 3/4 febrile neutropenia was observed in 10 (24%) despite no treatment-related deaths. The objective response rate and disease control rate (DCR, % pts with CR/PR/SD) was 82.9% and 97.6%, respectively. Median follow-up time was 15.6 months, and 1-yr PFS rate was 34.2% with 95% confidence interval (CI) of 20.3-48.5%, which met the primary endpoint. Also, 1-yr OS rate was 75.6% (95%CI: 59.4-86.1%). Exploratory analysis for pts with both EGFR- and ALK-wild-typed NonSq NSCLC (n = 16) demonstrated 1-yr PFS and OS rates of 50.0% (24.5-71.1%) and 87.5% (58.6-96.7%), respectively. Also, pts with maintenance therapy (n = 34) had 1-yr PFS and OS rates of 41.2% (24.8-56.9%) and 82.4% (64.9-91.7%), respectively. Conclusions: CDDP-DOC-BEV followed by BEV-PEM maintenance seems highly effective despite moderately toxic profiles in chemo-naïve pts with advanced NonSq NSCLC. Clinical trial information: UMIN000004127.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Ps

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.

Phase II trial of the c-Met inhibitor tepotinib in advanced lung adenocarcinoma with MET exon 14 skipping mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20541-e20541
Author(s):  
Paul K. Paik ◽  
Enriqueta Felip ◽  
Remi Veillon ◽  
Jürgen Scheele ◽  
Rolf Bruns
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Elevated Serum ◽  
Stage Iiib ◽  
Met Inhibitor ◽  
Grade 3 ◽  
Lung Adenocarcinomas ◽  
Platinum Doublet

e20541 Background: Approximately 3-4% of lung adenocarcinomas express a truncated form of c-Met (c-Metex14) due to mutation-induced exon 14 skipping. c-Metex14 accumulates on the cell surface and is constitutively active with the ability to drive NSCLC. Data suggest that lung adenocarcinomas harboring c-METex14 are sensitive to c-Met kinase inhibitors. The highly selective c-Met inhibitor tepotinib is well tolerated and active at an oral dose of 500 mg QD. This single-arm phase II trial (NCT02864992) is investigating the efficacy and safety of tepotinib in patients (pts) with advanced lung adenocarcinoma harboring METex14. Methods: Adults with stage IIIB/IV lung adenocarcinoma who have failed 1 or 2 lines of systemic therapy, including a platinum doublet-containing regimen, are eligible. Tumors must harbor mutations that are known to cause exon 14 skipping, confirmed by a central laboratory, but not activating EGFR mutations or ALK rearrangements. Pts receive tepotinib 500 mg QD until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. The primary endpoint is objective response rate. Secondary endpoints include progression-free and overall survival, safety, pharmacokinetics, and quality of life. Recruitment of 60 patients in Europe, USA, and Japan is planned. Results: Four pts (age 64–77 years; 3 stage IV, 1 stage IIIB, all Caucasian males) have been enrolled. All had received two prior chemotherapy regimens including a platinum doublet. Pts have currently completed 1–5 cycles of tepotinib therapy. The majority of adverse events observed to date have been grade 1/2 in severity; grade 3 disease-related dyspnea, pulmonary embolism, and pleural effusion were observed in one patient and grade 3 tepotinib-related elevated serum amylase in another. Of the 3 pts with post-baseline tumor evaluations, two have had an unconfirmed partial response and the third (with only one post-baseline assessment) stable disease. Conclusions: These initial data suggest that the efficacy of tepotinib 500 mg QD is comparable to that of less selective c-Met inhibitors in pts with c-METex14 NSCLC (ORR > 40%). Tepotinib is also well tolerated. Recruitment to the trial is ongoing. Clinical trial information: NCT02864992.

A phase II trial of weekly cisplatin and docetaxel in advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18150-18150
Author(s):  
M. A. Sovak ◽  
S. Lutzker ◽  
L. Guensch ◽  
M. Joyce ◽  
S. Schwartz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Significant Risk ◽  
Stage Iv ◽  
Median Number ◽  
Stage Iv Disease ◽  
Low Incidence ◽  
Grade 3 ◽  
Ecog Ps ◽  
Weekly Cisplatin

18150 Background: Every 3-week cisplatin doublets used to treat advanced NSCLC carry a significant risk of renal and other toxicities and can be difficult for patients with co-morbidities. To reduce these toxicities, we conducted a phase II study to evaluate the efficacy and toxicity of weekly cisplatin and docetaxel in advanced NSCLC. Methods: Eligibility included patients with advanced or recurrent NSCLC, ECOG PS of 0–1, and no prior chemotherapy for metastatic disease. This Cancer Institute of New Jersey network, single stage phase II clinical trial was designed to give 3 weekly doses of cisplatin at 25 mg/m2 and docetaxel at 35 mg/m2, followed by 1 week of rest, for a total of 6 cycles of therapy. Toxicity was monitored weekly, and disease evaluation was performed every 2 cycles. The primary endpoint was response rate (RR); secondary endpoints included time to progression (TTP), median and 1-year survival. Results: From 12/03 to 11/06, 36 patients were enrolled so far. The median age of patients is 63 (range 47–78), the majority is white (n=33), 29 have stage IV disease, and half (n=18) are women. Fourteen have an ECOG PS=0 and 22 with PS=1. Histologic subtypes are: adenocarcinoma (n=24), NSCLC NOS (n=7), squamous (n=5). Eleven patients received = 4 cycles of therapy; median number of cycles delivered is 2.5. Reasons for treatment discontinuation include completion of therapy (n=5), progression of disease (n=16), adverse events (n=8), and patient preference (n=4). Three patients continue on therapy at this time. No complete responses were yet observed; 8 patients (22%) achieved a partial response; 10 patients had stable disease, 10 patients progressed, and 8 came off study before first disease evaluation. Median TTP was 3.1 months (mo) (95% CI 2, 5.5), median survival is 8.3 mo (95% CI 5,16.2) and 1-year survival is 39% (95% CI 20, 57). Most toxicities were mild but also included neutropenia (grade 3, n=1; grade 4, n=1), neutropenic fever (n=1), renal toxicity (grade 3, n=2), nausea (grade 3, n=1), fatigue (grade 3, n=3), diarrhea (grade 3, n=4) and metabolic abnormalities (grade 3, n=3). Conclusion: Weekly cisplatin and docetaxel is well tolerated with a low incidence of toxicity and demonstrates activity similar to every 3-week treatment in patients with advanced NSCLC. No significant financial relationships to disclose.

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