Phase II trial of nab-paclitaxel (nanoparticle albumin-bound paclitaxel (ABX)) + capecitabine (XEL) in first-line treatment of metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1053-1053 ◽  
Author(s):  
B. G. Somer ◽  
L. S. Schwartzberg ◽  
F. Arena ◽  
A. Epperson ◽  
D. Fu ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Safety And Efficacy ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Reductions

1053 Background: ABX and XEL both have substantial single agent activity in MBC. Taxane and anti-metabolite doublets improve response rate and TTP and longer survival. ABX administered weekly has an excellent safety and efficacy profile with maintenance of dose intensity. This study was designed to test the safety and efficacy of ABX + XEL given in a novel combination schedule. Methods: This phase II, multicenter open label study utilized ABX 125 mg/m2 IV on day 1, 8 and with no premeds and capecitabine 825 mg/m2 PO BID days 1–14 on a Q 3 week cycle. The primary endpoint is objective response rate, with evaluation performed after every 2 cycles. Entry criteria include measurable MBC by RECIST criteria, age >18, PS 0–2, no prior chemo for metastatic disease, > 6 months since adjuvant fluoropyrimidine and/or paclitaxel. Results: The full sample of 50 patients (pts) have been enrolled; data from 43 pts are available for analysis. Median age is 58 (range 23.7–90.6). 37% received prior adjuvant anthracycline and 33% prior adjuvant taxane. Median number of metastatic sites is 2 (range 1–7), with most common sites of disease liver, 53.5%; bone, 51.2%; and lung, 14%. 226 cycles of therapy have been delivered. 5 pts required a dose reduction in XEL (3 pts to 650 mg/m2; 2 to 550 mg/m2) and 4 pts had dose reduction in ABX to 100 mg/m2. XEL dose reductions occurred due to hand-foot syndrome (3), neutropenia (1), and fatigue (1). ABX dose reductions occurred due to mucositis, diarrhea, fatigue, and neuropathy (1 pt each). 10 pts had grade 3–4 non-hematologic AEs: 3 hand-foot syndrome, 4 fatigue, and 3 GI. Hematologic AEs included 4 with grade 3 and 1 with grade 4 neutropenia, and 2 with grade 4 febrile neutropenia. The most common AEs of any grade were GI (30), dermatological (23), fatigue (15), neuropathy (12), and hand-foot syndrome (11). The incidence of Grade 1–2 neuropathy was 25% (no grade 3–4). Of 38 pts available for analysis of response, the overall response rate is 47.5%: PR 39.5%, CR 8%. Total of 15 pts have stable disease, 20 pts have completed 6+ cycles. No significant financial relationships to disclose.

Phase II trial of nanoparticle albumin-bound paclitaxel (ABX) + capecitabine (XEL) in first line treatment of metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10731-10731
Author(s):  
D. Mintzer ◽  
L. S. Schwartzberg ◽  
P. Cobb ◽  
D. Henry ◽  
A. Epperson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Open Label ◽  
Improve Response Rate ◽  
Safety And Efficacy ◽  
Grade 3

10731 Background: ABX and XEL both have substantial single agent activity in MBC. Taxane and anti-metabolic doublets improve response rate and TTP compared to singlet therapy. ABX given weekly has excellent safety and efficacy profile with maintenance of dose intensity. We designed this study to test the safety and efficacy of ABX + XEL given in a novel combination schedule. Methods: This phase II, multicenter open label study utilized ABX 125 mg/m2 IV on day 1, 8 and with no premeds and Xeloda 825 mg/m2 PO days 1–14 every three weeks. Entry criteria include measurable MBC by RECIST, no prior chemo for metastatic disease, > 6 months since adjuvant fluoropyrimidine and paclitaxel. A total of 50 patients (pts) are scheduled to be enrolled. Primary endpoint is objective response rate. Results: To date, 14 patients have entered on study. Safety analysis prespecified by the protocol is completed in the 1st six patients. No unique, unexpected or grade 4 toxicities have occurred. Two patients have grade 3 hand-foot syndrome, one had grade 3 neutropenia and one had grade 3 fatigue. Enrollment is continuing without change in dose/schedule. Response data is available in the first two cycles of therapy in 8 patients. At this point, two pts have achieved PR, four have stable disease and two have progressive disease. Conclusions: The combination of weekly ABX plus daily XEL orally at clinically effective doses is safe and shows preliminary evidence of efficacy. Complete enrollment of this trial is expected by May 2006 and updated results will be presented. [Table: see text]

Multi-institutional phase II study of carboplatin-gemcitabine combination chemotherapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18179-18179
Author(s):  
J. Sasaki ◽  
H. Uramoto ◽  
K. Kashiwabara ◽  
H. Kishi ◽  
E. Moriyam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Group Performance ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Efficacy And Safety ◽  
Grade 3

18179 Background: Because elderly pts may tolerate platinum-based combination chemotherapy poorly, single-agent chemotherapy is selected for the treatment regimen. However, retrospective subgroup analyses have consistently indicated that elderly pts indeed benefit from platinum-based combination chemotherapy as well as their younger counterparts. This phase II study evaluated the efficacy and safety of carboplatin-gemcitabine combination chemotherapy in elderly pts with advanced NSCLC. Methods: Fifty-four pts aged more than 70 years old (median, 77; range, 70–88) with previously untreated advanced NSCLC were enrolled on this trial. Additional criteria included the presence of measurable lesions, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Pts received carboplatin at an area under the curve of 4 mg/ml/min on the first day and gemcitabine at 1000 mg/m2 on the first and eighth day of consecutive 3 week periods. The primary endpoint was to determine the objective response rate of this platinum-doublet regimen. The RECIST criteria were used to measure response. Results: Enrolled pts included 15/39 with stage IIIB/IV diseases. Fifty-one out of enrolled pts were eligible for efficacy and safety analyses. The median number of treatment cycles was 4 (range, 1–7). Fifteen partial responses (response rate: 29%) were obtained. The median TTP was 118 days. Hematological toxicities of grade 3/4 included leukopenia (46%), neutropenia (72%) and thrombocytopenia (50%). Non-hematological toxicities of grade 3/4 included nausea (6%), appetite loss (7%), fatigue (7%) and infection (9%). Conclusions: The combination carboplatin-gemcitabine at these doses has shown activity with a favorable toxicity profile for fit elderly pts with advanced NSCLC. No significant financial relationships to disclose.

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

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

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

Capecitabine plus docetaxel (XT): A first line, phase II clinical trial in metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10624-10624
Author(s):  
C. L. Vogel ◽  
E. Tan-Chiu ◽  
F. Gokce
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Toxicity Profile ◽  
Nail Changes ◽  
The Mean ◽  
Dose Levels ◽  
Higher Doses ◽  
Dose Reductions

10624 Background: The XT combination originally published at (X) dosed at 1250 mg/m2 bid po x 14 days and (T) at 75 mg/m2 q3 weeks I.V. respectively yielded good response rates and an overall survival advantage compared with single agent docetaxel at 100 mg/m2. However, the toxicity profile of this regimen has led to major dose and schedule modifications by most oncologists. Methods/Results: We initiated a Phase II trial at doses of X at 900 mg/m2 bid po x 14 days and T at 36 mg/m2 d 1 and 8. Three responded and the mean no. of cycles for these patients was 3.8. Since four of 6 went off study because of toxicity two additional dose levels were studied in 6 patients each. A second cohort received X at 650 mg/m2 bid and T at 30 mg/m2. With 6 evaluable patients, four of 6 responded but all 4 required further dose reductions. Mean no. of cycles received was 4.2. A third cohort of 6 patients received X at 825 mg/m2 plus the lower T at 30mg/m2 who received a mean no. of cycles of 6. While only 1/6 responded 3 additional patients had stable disease with marked decreases in CEA or CA 15–3 suggestive of anti-tumor response. Only 1/6 required a dose reduction. Among the 18 patients, epiphora was described by 5 (28%). Only 3 patients developed significant leukopenia, and thrombocytopenia was not seen. T-induced nail changes were uncommon but were severe in one patient. Two patients at the first dose level, but only one at lower levels developed mucositis. Grade 1 anemia was common but managed easily with growth factor support. Conclusions: The response rate of 44% is encouraging with these lower doses of XT. We recommend further studies using X at 825 mg/m2 and T at 30mg/m2 since these doses were associated with encouraging response rate and a better toxicity profile than higher doses. Even at this higher dose of X dose reductions may well be needed. (Supported by a grant from Roche Laboratories, Inc.) No significant financial relationships to disclose.

Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group

2007 ◽  
Vol 25 (4) ◽  
pp. 356-361 ◽  
Author(s):  
Gilles Vassal ◽  
Dominique Couanet ◽  
Elizabeth Stockdale ◽  
Anne Geoffray ◽  
Birgit Geoerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Tumor Burden ◽  
French Society ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Multiagent Chemotherapy

PurposeThis phase II study was designed to evaluate the efficacy of irinotecan administered intravenously once every 3 weeks in pediatric patients with recurrent or refractory rhabdomyosarcoma.Patients and MethodsA total of 35 patients younger than age 20 years, with refractory or relapsed rhabdomyosarcoma for which standard treatments have failed, received irinotecan at 600 mg/m2administered as a 60-minute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and preventive antiemetic treatment. Tumor response was assessed every two cycles until progression according to WHO criteria.ResultsThe best overall response rate to irinotecan was 11.4% (95% CI, 3.2 to 26.7%; 2.9% complete responses, 8.5% partial responses) from all patients recruited. The median times to progression and survival were 1.4 and 5.8 months, respectively. A total of 112 cycles were administered, with a median number of two cycles per patient (range, 1 to 16). The most common grade 3/4 toxicities were neutropenia (46%), abdominal pain or cramping (17%), cholinergic syndrome (14%), nausea/vomiting (11%), anemia (11%), thrombocytopenia (9%), and diarrhea (6%).ConclusionIn heavily pretreated children with a high tumor burden who have been treated with multiagent chemotherapy, irinotecan administered intravenously as a single agent, at 600 mg/m2every 3 weeks, showed an interesting objective response rate and a good tolerance profile in rhabdomyosarcoma.

scholarly journals Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant

2020 ◽  
Vol 38 (5) ◽  
pp. 388-394 ◽  
Author(s):  
Jennifer K. Litton ◽  
Marion E. Scoggins ◽  
Kenneth R. Hess ◽  
Beatriz E. Adrada ◽  
Rashmi K. Murthy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dose Reduction ◽  
Response Rate ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Operable Breast Cancer ◽  
Pathologic Response ◽  
Pathogenic Variant ◽  
Grade 3

PURPOSE Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months in patients with a known germline BRCA pathogenic variant (g BRCA-positive) and operable breast cancer. METHODS Eligibility included 1 cm or larger invasive tumor and g BRCA-positive disease. Human epidermal growth factor receptor 2–positive tumors were excluded. Twenty patients underwent a pretreatment biopsy, 6 months of once per day oral talazoparib (1 mg), followed by definitive surgery. Patients received adjuvant therapy at physician’s discretion. The primary end point was residual cancer burden (RCB). With 20 patients, the RCB-0 plus RCB-I response rate can be estimated with a 95% CI with half width less than 20%. RESULTS Twenty patients were enrolled from August 2016 to September 2017. Median age was 38 years (range, 23 to 58 years); 16 patients were g BRCA1 positive and 4 patients were g BRCA2 positive. Fifteen patients had triple-negative breast cancer (estrogen receptor/progesterone receptor < 10%), and five had hormone receptor-positive disease. Five patients had clinical stage I disease, 12 had stage II, and three had stage III, including one patient with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma. One patient chose to receive chemotherapy before surgery and was not included in RCB analyses. RCB-0 (pathologic complete response) rate was 53% and RCB-0/I was 63%. Eight patients (40%) had grade 3 anemia and required a transfusion, three patients had grade 3 neutropenia, and 1 patient had grade 4 thrombocytopenia. Common grade 1 or 2 toxicities were nausea, fatigue, neutropenia, alopecia, dizziness, and dyspnea. Toxicities were managed by dose reduction and transfusions. Nine patients required dose reduction. CONCLUSION Neoadjuvant single-agent oral talazoparib once per day for 6 months without chemotherapy produced substantial RCB-0 rate with manageable toxicity. The substantive pathologic response to single-agent talazoparib supports the larger, ongoing neoadjuvant trial (ClinicalTrials.gov identifier: NCT03499353 ).

Randomized phase II study of low (100mg) versus intermediate (400mg) doses of thalidomide (Thal) plus DTIC in metastatic melanoma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8048-8048
Author(s):  
R. Von Moos ◽  
R. Dummer ◽  
R. Inauen ◽  
T. Ruhstaller ◽  
S. Meier ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Haematological Toxicity ◽  
Stage Iv ◽  
Clinical Activity ◽  
Thromboembolic Events ◽  
Grade 3

8048 Background: Single agent DTIC is the standard therapy for MM. In an effort to improve the response rate (DTIC 7–13%), Thal, a molecule with antiangiogenic effect was added in two different dosages to DTIC. Methods: Eligibility: Stage IV MM, ECOG performance status 0–2, no prior treatment with DTIC or Thal. Design: Randomized multicenter phase II Bryant and Day 2-stage optimal design with 20 patients (pats) per arm. Treatment regimens: DTIC 200mg/m2 d1–5 q3w plus Thal (100 versus 400mg per day). Responses were assessed every two cycles. Endpoints: Toxicity, feasibility, response rate (RR) and time to treatment failure (TTF). Results: 26 pats (12 male/ 14 female) at a median age of 58 years (range 24–82) with stage IV melanoma (M1a-2, M1b-2, M1c-22) were enrolled between 2001–2005 and received a median of 4 cycles (1–6). All the pats were evaluated for toxicity, 25 (96%) were assessable for objective response (WHO criteria). The overall response rate of the evaluable patients was 27% (100mg, RR 25%; 400mg, RR 33%), one patient (4%) had a complete response, 6 pats (23%) had a partial response, 11 pats had stable disease (42%), and 7 pats (27%) progressed. The median TTF was 5.2 months. Using NCI 2.0 Common Toxicity Criteria, grade 3 haematological toxicity was 12% (anemia-1, leucopenia-1, thrombocytopenia-1). Cumulative non-haematological toxicity grade 3/4 was 35% including fatigue in 5 pats (all on 400mg Thal arm), thromboembolic events in 2 (1 each treatment arm) and bleeding in 2 (1 cerebral). Polyneuropathy and constipation were a minor problem (no grade 3/4). The 400mg Thal arm was stopped according to the protocol because of intolerable fatigue in 5 out of 6 patients. Two of the first 14 pats suffered from pulmonary embolism. Thromboprophylaxis with low molecular weight heparin (LMWH) was mandatory after an amendment . Thereafter no thromboembolic events were seen but one fatal cerebral bleeding occurred in one patient. Conclusions: 400mg Thal in combination with DTIC was not feasible due to toxicity. 100mg Thal was well tolerated and showed significant clinical activity. Using our low dose Thal regimen prophylactic LMWH is necessary to prevent severe thromboembolic events. No significant financial relationships to disclose.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

DEDUCTIVE: A study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma—Phase Ib results.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 294-294
Author(s):  
Renuka V. Iyer ◽  
Daneng Li ◽  
Farshid Dayyani ◽  
Alexandria T. Phan ◽  
Michael N. Needle ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Primary Objective ◽  
Advanced Hepatocellular Carcinoma ◽  
Cross Sectional ◽  
Advanced Hcc ◽  
Grade 3 ◽  
Improve Patient

294 Background: A recent ph3 study combining bevacizumab (VEGF-A Mab) with atezolizumab (PD-L1 inhibitor) has shown significant improvements in OS and PFS demonstrating that a combination of VEGF and PDL1 inhibition can improve patient outcomes over sorafenib. Tivozanib (T, a potent and selective VEGFR 1, 2 & 3 TKI) and durvalumab (D, a PD-L1 antibody) have both demonstrated single agent activity in HCC and have been combined safely with other therapies. T blocks all three VEGF receptors, and when combined with a PD-L1 inhibitor may improve patient outcomes. The ph1 portion of this study combines T with D to establish the recommended phase II dose (RP2D) and provide preliminary safety and efficacy data. Methods: Major eligibility criteria are adults with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance > 40 ml/min. Major exclusion criteria are co-infection with HBV and HCV and significant organ dysfunction. The starting dose is the combination of T 1 mg orally for 21 days followed by 7 days off treatment and D 1500 mg intravenously every 28 days. A DLT is generally defined as the occurrence of any Grade ≥3 immune or non-immune adverse event (AE) in Cycle 1 that is at least possibly related to the investigational regimen other than any grade of vitiligo or alopecia or Grade 3 controllable hypertension in cycle 1. The primary objective is to establish the RP2D and the safety and tolerability for this combination in patients with advanced HCC. Patients will be treated until progression of disease, unacceptable side effects, or death. Outcome measures will be AEs per CTCAE v.5 and cross-sectional imaging performed every 8 weeks. Results: Seven patients were enrolled in phase I. Six were male; the median age was 75 (range 40 to 82). One patient had mild elevation of LFTs and did not complete the 21-day course of T and was replaced. No patient experienced a >=grade 3 AE in cycle 1. The most common AEs, each seen in two of seven patients, were anorexia, cough, diarrhea, dysphonia, fatigue, hypertension, and palmar-plantar erythrodysesthesia. Two of seven have achieved a partial response. Conclusions: The combination of T with D in patients with untreated advanced HCC is well tolerated. The RP2D for the combination is T 1 mg orally for 21 days on treatment followed by 7 days off treatment and D 1500 mg intravenously every 28 days. In the phase II portion of the study an additional 30 patients will be treated at the RP2D. Secondary objectives are to assess the objective response rate, progression free survival, and overall survival in this population. Clinical trial information: NCT03970616.

scholarly journals Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study

2020 ◽  
Vol 38 (24) ◽  
pp. 2753-2761 ◽  
Author(s):  
Caicun Zhou ◽  
Xingya Li ◽  
Qiming Wang ◽  
Guanghui Gao ◽  
Yiping Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Unmet Need ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Grade 3

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

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