Phase II trial of paclitaxel, ifosfamide, and cisplatin (TIP) for previously untreated patients (pts) with intermediate- or poor-risk germ cell tumors (GCT).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 336-336 ◽  
Author(s):  
Darren Richard Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Sujata Patil ◽  
Lindsay Joy Van Alstine ◽  
...  
Keyword(s):  
Phase Ii ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Neutropenic Fever ◽  
Intermediate Risk ◽  
Stage Design ◽  
Poor Risk ◽  
Secondary Endpoints ◽  
Grade 3

336 Background: Durable progression-free survival (PFS) rates for pts with intermediate- and poor-risk GCT approximate only 75% and 50%, respectively with standard BEP chemotherapy. This phase II study investigated first-line TIP in this population. Methods: Pts age ≥18 with previously untreated poor-risk or modified intermediate-risk (LDH ≥3x upper limit of normal [ULN]) GCT were eligible. Four cycles of TIP were given every 21 days, consisting of paclitaxel 120mg/m2 on days 1-2; ifosfamide 1200mg/m2 (with mesna support) on days 1-5; and cisplatin 20mg/m2on days 1-5. Peg-filgrastim was given on day 6 and levofloxacin on days 7-13 for prevention of neutropenic fever. The primary endpoint was the complete response (CR) rate; secondary endpoints included PFS and toxicity. A Simon’s two-stage design was used: if ≥11 CRs were observed in the first 18 pts, a total of 41 evaluable pts would be accrued with the trial considered positive if ≥27 CRs were achieved. Results: Of 44 men (median age 27 [range 18-56]) enrolled; 38 had nonseminoma and 6 had seminoma; 29 were poor-risk and 15 intermediate-risk. Primary site was testis in 30, mediastinum in 11, retroperitoneum in 3. Most pts had lung (n=31) and abdomen/pelvis (n=29) metastasis, and 14, 6, and 1 had liver, bone, and brain metastasis, respectively. Markers were elevated in 42 pts. Forty pts received all 4 TIP cycles; 3 pts were withdrawn after 2 cycles for allergic reactions to paclitaxel and were inevaluable for response, and 1 pt completed only 3 cycles in order to undergo surgery for growing teratoma syndrome (evaluable). Of 41 evaluable pts, 29 (72%, 90% CI: 60% – 78%) achieved a CR and 5 (all seminoma) achieved a PR with negative markers (PR-); 7 pts had incomplete responses and 2 pts relapsed from PR- or CR. With a median follow-up of 2.1 years, estimated 1-year PFS was 79% (95% CI: 64% – 89%) and 3-year overall survival 97% (95% CI: 83% – 100%). There were no toxic deaths. Grade 3/4 toxicities were primarily hematologic but only 7 (16%) pts developed neutropenic fever. Conclusions: TIP demonstrated promising efficacy and was tolerable in intermediate- and poor-risk GCT pts. A randomized trial of TIP versus BEP is being planned. Clinical trial information: NCT00470366.

Paclitaxel, ifosfamide, and cisplatin (TIP) efficacy for first-line treatment of patients (pts) with intermediate- or poor-risk germ cell tumors (GCT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4501-4501
Author(s):  
Darren Richard Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Sujata Patil ◽  
Lindsay Joy Van Alstine ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Complete Response ◽  
Neutropenic Fever ◽  
First Line ◽  
Poor Risk ◽  
Study Results ◽  
Secondary Endpoints ◽  
Grade 3

4501 Background: Durable progression-free survival (PFS) rates for pts with intermediate- and poor-risk GCT approximate only 75% and 50%, respectively with standard BEP. This multicenter phase II study investigated first-line TIP in this population. Methods: Pts age ≥18 with untreated, IGCCCG intermediate- (LDH modified to ≥3x upper limit of normal) or poor-risk GCT were eligible. Pts received 4 cycles of TIP every 21 days, consisting of paclitaxel 120mg/m2 days 1-2; ifosfamide 1200mg/m2 days 1-5; and cisplatin 20mg/m2days 1-5, followed by G-CSF and levofloxacin for neutropenic fever prophylaxis. The primary endpoint was the complete response (CR) rate; secondary endpoints included PFS and toxicity. A Simon’s 2-stage design required a CR in ≥11/18 pts to proceed to stage 2, where with ≥27/41 CRs overall, the regimen would be considered active and worthy of further study. Results: Of 44 men (median age 27) enrolled; 38 had nonseminoma and 6 seminoma; 29 were poor-risk and 15 intermediate-risk. Primary site was testis in 30, mediastinum in 11, and retroperitoneum in 3. 42 pts had elevated markers and 14, 6, and 1 had liver, bone, and brain metastasis, respectively. The trial met its primary endpoint; of 41 evaluable pts, 28 achieved a CR (see Table) and 6 pts (5 with seminoma) achieved a partial response with negative markers (PR-). Two pts relapsed. With a median follow-up of 2.2 years, estimated 3-year PFS was 79% and 3-year overall survival (OS) 98% (see Table). There were no treatment-related deaths. Grade 3/4 toxicities were primarily hematologic and 6 (14%) pts developed neutropenic fever. Conclusions: TIP demonstrates promising efficacy and is well-tolerated in intermediate- and poor-risk GCT pts. A randomized trial of TIP vs. BEP has been initiated to compare efficacy. Clinical trial information: NCT00470366. [Table: see text]

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]

Lenvatinib plus pembrolizumab combination therapy in patients with radioiodine-refractory (RAIR), progressive differentiated thyroid cancer (DTC): Results of a multicenter phase II international thyroid oncology group trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6512-6512 ◽  
Author(s):  
Bryan Haugen ◽  
Jena French ◽  
Francis P. Worden ◽  
Bhavana Konda ◽  
Eric Jeffrey Sherman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Time ◽  
Phase Ii ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maculopapular Rash ◽  
Multicenter Phase ◽  
Secondary Endpoints ◽  
Grade 3

6512 Background: Lenvatinib is an approved therapy for patients with RAIR DTC. While the overall response rate (ORR) is high, few patients achieve a complete response (CR) and most patients eventually have progressive disease (PD). Combination lenvatinib and pembrolizumab is being explored in many different cancers, and this combination has been approved for advanced endometrial carcinoma. Methods: Patients with RAIR DTC with Response Evaluation Criteria in Solid Tumor (RECIST v1.1) measurable PD (<14 months (mo) prior to registration) were enrolled in this single-arm multicenter phase II study. Patients were excluded if they had received previous VEGFR-directed multikinase therapy. The lenvatinib starting dose was 20 mg/day orally and pembrolizumab was 200mg IV every 3 weeks. The primary endpoint was CR. ORR, progression-free survival (PFS) and safety graded by Common Terminology Criteria for Adverse Events v4.0 were secondary endpoints. Results: Thirty patients were enrolled. The median age was 62.5 years, and 53% of the patients were women. Seventy percent of patients had grade 3 adverse events (AEs) and 10 percent had grade 4 AEs. There were no treatment-related deaths. The most common > grade 3 AEs were hypertension (47%), weight loss (13%), maculopapular rash (13%), leukopenia (7%), diarrhea (7%) and oral mucositis (7%). Twenty-one patients (70%) required lenvatinib dose reduction. Of 29 evaluable patients, 18 (62%) had a partial response (PR) and 10 (35%) had stable disease (SD). The clinical benefit rate (ORR +SD) was 97%. Median time to tumor nadir was 7.4 mo (1.6-17.8 mo). Median PFS was not yet reached. The PFS at 12 months was 74%. Median time on therapy was 9.9 mo (3.2-18.9 mo). Fourteen patients are continuing therapy (7.6-18.9 mo). Six of these patients (43%) have not yet reached tumor size nadir. Three patients (10%) had > 80% target tumor shrinkage. Conclusions: Lenvatinib plus pembrolizumab is reasonably tolerated in patients with RAIR DTC. To date, there have been no documented complete responses. Combination lenvatinib plus pembrolizumab therapy has a high ORR in patients with RAIR DTC. Continuation of this study will help determine the depth and length of the responses. Clinical trial information: NCT02973997 .

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and prolonged stable disease observed in adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 91-91
Author(s):  
Geoffrey Y. Ku ◽  
Yelena Yuriy Janjigian ◽  
Manish A. Shah ◽  
Jessica Herrera ◽  
Laura H. Tang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Secondary Endpoints ◽  
Grade 3

91 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial of sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We performed a phase II trial of single-agent sorafenib with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response and toxicity. Methods: Patients (Pts) with measurable metastatic E and GEJ cancer with ≤3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Thirty-five patients have been accrued, with 34 evaluable; median age 62, 31 male, 4 female, median KPS 80%, E 25, GEJ 10, adenocarcinoma (AC) 30 squamous 5, median no. of prior therapies 2. Of 31 response-evaluable Pts, 1 (3%) ongoing complete response was noted (34+ months) in a Pt with E AC with biopsy-proven lymph node recurrence after chemoradiation and surgery; 23 Pts (74%) had stable disease. Median PFS is 3.7 months (95% CI 1.9 to 4 months), with median overall survival 8.9 months (95% CI 6.9 to 11.6 months). Four patients remain on treatment. Significant grade 3 toxicities included hand foot reaction (3 Pts), rash (1 Pt), dehydration (3 Pts) and fatigue (2 Pts). Twenty-seven of 33 tumors (82%) tested positive for phospho-ERK by immunohistochemistry. Conclusions: Encouraging activity in terms of PFS has been noted in this heavily pre-treated population. Updated data will be presented. Supported by a grant from Bayer. Clinical trial information: NCT00917462.

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

Efficacy of nivolumab/ipilimumab in patients with initial or late progression with nivolumab: Updated analysis of a tailored approach in advanced renal cell carcinoma (TITAN-RCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4576-4576
Author(s):  
Marc-Oliver Grimm ◽  
Emilio Esteban ◽  
Philippe Barthélémy ◽  
Manuela Schmidinger ◽  
Jonas Busch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Remission Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Poor Risk ◽  
Secondary Endpoints ◽  
Tailored Approach

4576 Background: TITAN-RCC uses a tailored immunotherapy approach in renal cell carcinoma (RCC), starting with nivolumab (nivo) induction followed by nivo + ipilimumab (ipi) as immunotherapeutic “boost” in non-responders. Patients with initial partial or complete response (PR/CR) continued with nivo maintenance but received later “boosts” for progressive disease (PD). Here we report updated results focusing on the efficacy of nivo+ipi in patients with initial PD vs. initial responders with later PD. Methods: Patients with IMDC intermediate and poor risk advanced clear cell RCC were recruited between OCT 2016 and DEC 2018. Patients started with nivo 240 mg Q2W induction. Patients with early significant PD (week 8) or non-responders at week 16 received 2-4 nivo+ipi “boost” cycles. Responders (PR/CR) to nivo monotherapy continued with maintenance but could receive nivo+ipi for later PD. The primary endpoint is confirmed investigator assessed objective response rate (ORR) per RECIST in first line (1L) and second line (2L). Secondary endpoints included activity of nivo monotherapy, remission rate with nivo+ipi “boost”, safety and overall survival (OS). Results: 109 1L and 98 2L (after TKI) patients were analyzed for efficacy. Median age was 65 years (range 20-87). 71 % were intermediate and 25 % poor risk. Confirmed ORR with nivo monotherapy was 28 % for 1L and 17 % for 2L. After a median follow-up of 12.8 months best overall response after nivo induction ± nivo+ipi was 36 % in 1L and 30 % in 2L. Of all patients, 38 received nivo+ipi for stable disease (SD) up to week 16, with 1 (3 %), 4 (11 %) and 26 (68 %) achieving CR, PR and SD, respectively. 28 patients in 1L and 43 in 2L were boosted with nivo+ipi for initial PD. Of these, 3 (11 %) and 8 (29 %) achieved PR and SD, respectively, in 1L, whereas 3 (7.0 %) achieved CR, 6 (14 %) PR and 13 (30 %) SD in 2L. 16 and 10 patients received “boosts” later than week 16 for PD during nivo maintenance in 1L and 2L, respectively. Thereof, 3 (19 %) achieved PR and 5 (31 %) SD in 1L, whereas 2 (20 %) achieved PR and 3 (30 %) SD in 2L. Progression-free survival was 6.3 months (95 % CI 3.7 – 10.1) and 3.7 months (95 % CI 2.0 - 4.5) in 1L and 2L, respectively. OS was 27.2 months (95 % CI 19.9 – not estimable (NE)) in 1L and 20.2 months (95 % CI 15.6 – NE) in 2L. Treatment-related adverse events will be presented. Conclusions: Our tailored approach with nivo+ipi “boosts” results in improved response rates compared to nivo monotherapy. Our updated analysis suggests that almost half of the patients receiving “boosts” for PD improve to either PR/CR (18 %) or SD (30 %), irrespective of initial or later progression with nivo. Clinical trial information: NCT02917772. [Table: see text]

Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study

1999 ◽  
Vol 17 (1) ◽  
pp. 25-25 ◽  
Author(s):  
M. J. Byrne ◽  
J. A. Davidson ◽  
A. W. Musk ◽  
J. Dewar ◽  
G. van Hazel ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Symptom Improvement ◽  
Median Response ◽  
Grade 3

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

scholarly journals Irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma: a single-arm, three-centre, prospective study

2020 ◽  
Vol 12 ◽  
pp. 175883592097084
Author(s):  
Keke Nie ◽  
Ling Zhang ◽  
Yunhong You ◽  
Hongmei Li ◽  
Xiuhui Guo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Pancreatic Adenocarcinoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Patient Death ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Secondary Endpoints ◽  
Study Population ◽  
Grade 3 ◽  
Moderate Nausea

Objective: To study the efficacy and toxicity of irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma. Patients and methods: Previously untreated patients with cytologically or histologically confirmed metastatic pancreatic adenocarcinoma underwent a treatment regimen consisting of an intravenous infusion of irinotecan 165 mg/m2 and oxaliplatin 85 mg/m2 on day 1, and oral S-1 40 mg/m2 twice daily on days 1–14, repeating the regimen every 21 days until one of the following occurred: disease progression, intolerable toxicity, or patient death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate, toxicity, and quality of life. This ongoing study had been registered on ClinicalTrials.gov, NCT03726021. Results: A total of 41 patients were enrolled in this study, 18 men and 23 women. The median PFS was 4.33 months [95% confidence interval (CI): 2.83–5.88] and the median OS was 11.00 months (95% CI: 9.16–12.84). There were no instances of a complete response; the partial response, stable disease, and disease progression rates were 39.02% (16/41), 29.27% (12/41), and 31.71% (13/41), respectively. The most common adverse side effects were mild to moderate nausea, vomiting, neutropenia, and thrombocytopenia. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 29.27% (12/41) and 12.20% (5/41) of the patients, respectively. No treatment-related death was observed. Conclusion: Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. A larger study population is needed for further evaluation.

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.

Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGF pathway-activated stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400D.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9055-9055 ◽  
Author(s):  
Charu Aggarwal ◽  
Mary Weber Redman ◽  
Primo Lara ◽  
Hossein Borghaei ◽  
Philip C. Hoffman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Grade 5 ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

9055 Background: LungMAP is a National Clinical Trials Network umbrella trial for previously-treated SqNSCLC. S1400D is a phase II biomarker-driven therapeutic sub-study evaluating the FGFR inhibitor AZD4547 in patients (pts) with FGFR positive chemo-refractory SqNSCLC. Methods: Eligible pts had tumor FGFR alteration and/or mutation by next generation sequencing (Foundation Medicine), measurable disease, Zubrod PS 0-2, progression after 1 line of systemic therapy, and adequate end organ function. Receipt of prior immunotherapy was allowed. Eligible pts received AZD4547 80 mg bid orally. Primary endpoint was overall response rate (ORR) by RECIST; secondary endpoints included progression-free survival (PFS) and duration of response (DoR). Originally designed as a randomized trial of AZD4547 versus docetaxel, it was redesigned to be a single arm AZD4547 trial with the emergence of immunotherapy as standard 2ndline therapy. Forty pts were required to rule out an ORR of < = 15% if the true ORR was > 35% (90% power, alpha 0.05). Results: 93 pts (13% of pts screened on S1400) were assigned to S1400D; 43 were enrolled with 28 receiving AZD4547. Pt characteristics: median age 66.3 y (49-88), female (n = 8, 29%), & Caucasian (n = 25; 89%). Biomarker profile: FGFR1 amplification (n = 38; 86%); FGFR3 S249C (n = 4; 9%); FGFR3 amplification (n = 3; 7%); and FGFR3 fusion (n = 2; 5%). Nine pts (26%) had more than one biomarker alteration. The study was closed at interim analysis for futility in October 2016. Treatment related Grade 3 AEs were seen in 5 pts (dyspnea, fatigue, hyponatremia, lung infection & retinopathy); 1 pt had Grade 4 sepsis. There were no Grade 5 AEs. Median follow up among alive pts was 4.3 months (mos). Of 25 response evaluable pts, one with FGFR3 S249C had unconfirmed PR (4%, 95% CI 1-20%) with DoR of 1.5 mos. Median PFS was 2.7 mos (95% CI 1.4 - 4.3 mos). Conclusions: This is the first Phase II trial to evaluate AZD4547 as a targeted approach in pts with previously treated FGFR-altered SqNSCLC. AZD4547 had an acceptable safety profile but minimal activity in this biomarker-enriched cohort. Evaluation of other targeted agents in LUNG-MAP is currently ongoing. Clinical trial information: NCT02965378.

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