Phase II study of efficacy of bevacizumab and erlotinib in inoperable previously untreated hepatocellular carcinoma (HCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15557-e15557
Author(s):  
R. Govindarajan ◽  
E. Siegel ◽  
I. Makhoul ◽  
S. Williamson
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Synergistic Activity ◽  
Time To Progression ◽  
Class A ◽  
Pugh Class

e15557 Background: New treatment options are needed for patients with inoperable and metastatic HCC. Sorafenib, a RAF kinase inhibitor, prolongs the time to progression and overall survival compared to best supportive care (5.5 and 10.7 months respectively). Angiogenesis plays important role in the development and progression of HCC. Erlotinib, an EGFR tyrosine kinase inhibitor that down-regulates expression of Vascular Endothelial Growth Factor (VEGF), and bevacizumab, a monoclonal anti-VEGF antibody, have synergistic activity in arresting angiogenesis. The objective of the study was designed to evaluate the efficacy of the combination of bevacizumab and erlotinib. The pre-determined endpoint for a positive result is a 27 week PFS of > 20%. Methods: A phase II study was conducted for newly diagnosed unresectable or metastatic HCC, Child-Pugh class A or B cirrhosis with bilirubin <2.0 mg/dL, transaminases < 5 x ULN, Platelet count >75,000 K/UL and ECOG PS 0–2 who had no prior systemic therapy and were not candidates for liver transplantation. Erlotinib was administered continuously at a daily dose of 150 mg, and bevacizumab was administered at a dose of 15 mg/kg intravenously every three weeks. Subjects were evaluated for disease progression by RECIST criteria. Results: At the time of analysis, 21 subjects were enrolled (16 Child- Pugh class A, 5 class B). 16 were evaluable. The median age was 60 Yrs.(range 33–81). Four subjects (27%) were progression-free at 27 weeks of enrollment (95% CI 8%- 55%). Median (quartiles) time to progression was 10.3 (9.0–57.1) weeks. The median (quartiles) overall survival (OS) was 59.7 (range 24.6- 92.6) weeks. Grade-3 events observed were (no.): fatigue (4), dehydration (2), hematemesis (1), diarrhea (1), nausea (1), and dyspnea (1). Grade-4 events (no.) observed were: myocardial infarction (1), atrial fibrillation (1), and ventricular tachycardia (1); pulmonary edema (1). Conclusions: The results met the predetermined study end point of progression free survival at 27 weeks of > 20%. The combination of bevacizumab and erlotinib should be further evauated as treatment option for patients with HCC. [Table: see text]

Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group

2007 ◽  
Vol 25 (22) ◽  
pp. 3296-3301 ◽  
Author(s):  
Christopher W. Ryan ◽  
Bryan H. Goldman ◽  
Primo N. Lara ◽  
Philip C. Mack ◽  
Tomasz M. Beer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Renal Carcinoma ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Interferon Alfa

Purpose This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma. Patients and Methods Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 × 106 U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate. Results Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens. Conclusion The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.

A phase II study of docetaxel (D) plus imatinib (I) in patients with previously treated non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18200-18200
Author(s):  
L. A. White ◽  
A. M. Schmidt ◽  
N. N. Sjak-Shie ◽  
A. O. Greco ◽  
B. Cronin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Synergistic Activity ◽  
Weekly Schedule ◽  
Study Results ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

18200 Background: Docetaxel(D) has been shown to improve overall survival in pts with previously treated NSCLC. Pre-clinical data suggest synergistic activity with the combination of D and I. Paul Matthew; et al demonstrated the safety of this combination in pts with prostate cancer. Methods: This is a Phase II study of the combination of D and I in prev tx NSCLC to determine response rate, toxicity and assess overall survival. Pts must have received at least 1 prior regimen and have an ECOG PS of 2 or less. Prior tx with D was allowed. D was admin at 30 mg/m2 on a weekly schedule for 3 weeks followed by 1 week rest. I was admin at a starting dose of 600 mg/day throughout the study. Results: A total of 10 pts were enrolled. Seven male and 3 female with a median age of 66 years (range 58 - 74). A total of 26 cycles were delivered to 10 pts (mean = 3). Responses included 1 PR/3SD/2PD/4NE. One pt with a PR responded after cycle 4 but progressed after cycle 6. One pt maintained SD for 21 wks then expired due to an unrelated PE (h/o peripheral vascular disease). Grade 4 toxicity included periorbital edema (1 pt), pneumonia (2 pts), diarrhea (1 pt), dehydration (1 pt), dyspnea (1pt), anorexia (1 pt), pleural effusion (1 pt), and neutropenia (2 pts). Grade 3 toxicity included hyponatremia (1 pt), renal failure (1 pt), hypotension (2 pts), mental status changes (1 pt), anorexia (1 pt), azotemia (1 pt), dyspnea (1 pt), herpetic esophageal ulcer (1 pt), pneumonia (1 pt), neutropenia (2 pts), weakness & fatigue (1 pt), and anemia (1 pt). Four of 10 pts received only 1 cycle. (Three of those 4 suffered a fatal adverse event during cycle 1, not felt to be treatment related. The fourth developed herpetic esophageal lesions and was taken off study prior to tumor assessment.) Conclusions: The study was closed before the initial planned pts were enrolled due to low activity and unexpected high tox. Only 1 of 10 pts achieved a PR. Stable disease was observed in 3 pts but was of short duration in 2 of the 3. Despite supportive treatment, nausea, vomiting, diarrhea, and anorexia were difficult to control. Hematologic toxicity was encouragingly infrequent with only 2 pts experiencing Grade 4 neutropenia. Alternative dosing schedules would be recommended before pursuing this combination in NSCLC pts. Study supported by a grant from Novartis. No significant financial relationships to disclose.

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]

A multicenter random assignment phase II study of irinotecan and flavopiridol versus irinotecan alone for patients with p53 wild-type gastric adenocarcinoma (NCI 8060).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14586-e14586 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Laura H. Tang ◽  
Stephen Shibata ◽  
David Paul Kelsen ◽  
Michal Segal ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Wild Type

e14586 Background: Preclinical studies demonstrate that tumors wild-type for p53 (p53wt) are refractory to irinotecan relative to non-functional or mutant p53, and that sequential therapy with flavopiridol, a cyclin dependent kinase inhibitor that inhibits homologous recombination and DNA repair, and irinotecan overcomes p53 mediated drug resistance in vivo. This phase II study is designed to assess cell cycle mediated drug resistance in p53wt gastric cancer, and test the hypothesis that administration of flavopiridol following irinotecan can overcome resistance to irinotecan. Methods: Pts with advanced p53wt (≤ 20% nuclear IHC staining using D07 antibody) gastric adenocarcinoma and disease progression on non-irinotecan chemotherapy regimen were randomized in 2:1 fashion to irinotecan 100 mg/m2 followed 7 h later by flavopiridol 60 mg/m2 administered over 1h or irinotecan 100 mg/m2 administered weekly on a 2 week on/1 week off schedule. Response assessment is performed every 2 cycles and the primary endpoint is 3-month progression free survival (PFS). Pre- and post-treatment biopsies were obtained for molecular assessments of p53 mediated drug resistance. Results: To date 30 of 55 patients screened were p53wt (54%), 19 pts were randomized to receive irinotecan + flavopiridol (n=13) and irinotecan (n=6). Median characteristics of 19 evaluable patients: age 61 (44 to 76), KPS 80% (70 to100), 13 male, 1 prior regimen (1 to 2). The common treatment emergent toxicities were anemia (Grade 2/3 21%), neutropenia (grade 2/3 31%, grade 4 .05%), nausea (grade 2/3 21%) and fatigue (grade 2/3 37%). With irinotecan + flavopiridol 1/13 (8%) confirmed partial response was seen and 5 month disease stabilization in 3/13 (23%) patients. No responses were seen with single agent irinotecan. The median PFS was similar, 1.6 mos irinotecan + flavopiridol vs 1.3 mos in irinotecan group (p=0.21). Conclusions: 54% of gastric cancers are p53wt. Correlative tissue analysis including p53 sequencing, p21, Rad51 is ongoing. Due to lack of activity with irinotecan alone, an amendment to a single arm irinotecan + flavopiridol study is planned.

Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma (mRCC): A G.I.O.N. trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16081-e16081 ◽  
Author(s):  
Camillo Porta ◽  
Vittorio D. Ferrari ◽  
Paolo Andrea Zucali ◽  
Giuseppe Fornarini ◽  
Antonio Bernardo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Stage Design ◽  
Free Survival ◽  
Prospective Phase ◽  
Grade 3

e16081 Background: Sunitinib is a 1st-line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1st-line Sunitinib and 2nd-line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1st-line Sunitinib with a Disease Control Rate lasting at least 10 months, 2nd-line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter and spontaneous pneumothorax were also reported, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2nd-line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.

Phase II study of apatinib: A novel VEGFR inhibitor in pretreated patients with metastatic penile cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS538-TPS538
Author(s):  
Sheng Zhang ◽  
Fei Liang
Keyword(s):  
Phase Ii ◽  
Penile Cancer ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Efficacy Analysis ◽  
Efficacy Assessment ◽  
Pretreated Patients ◽  
Vegfr Inhibitor

TPS538 Background: Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2 and has been approved as monotherapy for treatment of metastatic gastric cancer in China. This phase II study aims to evaluate the efficacy and safety of apatinib monotherapy in pretreated patients with metastatic penile cancer in China (all patients have failed cisplatin-based chemotherapy previously). Methods: From October 2016 to May 2018, 9 patients were enrolled, and eight patients were eligible for efficacy analysis. All patients received apatinib 500 mg/day p.o. in a 4-week cycle, with the endpoint progression-free survival (PFS). This trial is ongoing. Longer follow-up and complete enrollment are needed for the final efficacy assessment. Clinical trial information: UMIN000021849.

RTOG 0131: Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligodendrogliomas: Relationship between 1p/19q status and progression-free survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1517-1517 ◽  
Author(s):  
M. A. Vogelbaum ◽  
B. Berkey ◽  
D. Peereboom ◽  
C. Giannini ◽  
R. Jenkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Median Time ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Chromosome 8 ◽  
Newly Diagnosed ◽  
Time To Progression ◽  
Durable Response ◽  
Free Survival

1517 Background: In a previous report, we showed in patients with newly diagnosed anaplastic oligodendrogliomas (AOs) and mixed anaplastic oligoastrocytomas (MAOs) that temozolomide (TMZ) can be given concurrently with radiation therapy (RT) with acceptable toxicity. We have now evaluated the efficacy of this regimen and correlated durability of response with tumor 1p/19q genotype. Methods: A phase II study was performed to evaluate the use of pre-RT TMZ followed by concurrent RT and TMZ in patients with newly diagnosed AO or MAO. The primary endpoint was to determine the pre-RT TMZ six-month progression rate, and secondary endpoints included progression-free survival and overall survival. Results: 40 eligible patients were entered into the trial. Thirty-two patients completed 6 months of pre-RT TMZ and concurrent RT and TMZ. Of the remaining eight patients, 4 withdrew due to toxicity and 4 other patients withdrew from study without evidence of toxicity or pre-RT progression. 1p/19q data are available in 37 cases; 23 tumors had loss of heterozygosity (LOH) of both 1p and 19q (double-deleted) while 14 tumors had LOH of either 1p or 19q (n = 3), or no LOH (n = 11). To date, 11 patients have experienced tumor progression; 1p/19q data are available for 10 of these cases (2 are double-deleted (2/23 = 9%), 8 have at least one intact chromosome (8/14 = 57%). Kaplan-Meier analysis demonstrates that progression free survival is significantly better for the double-deleted group (median time to progression not reached) than for the intact group (median time to progression = 15.2 months, p = 0.001). Overall survival is 98% (39/40) with a median follow-up of 17.5 months (2.8 - 31.1 months). Conclusions: LOH of both 1p and 19q is strongly correlated with a durable response of AO and MAO to a combined regimen of chemotherapy and radiation therapy. Tumors that are intact at 1p and/or 19q progress early despite an aggressive therapeutic regimen. These results suggest that future clinical trials should be prospectively stratified by tumor 1p/19q genotype. [Table: see text]

Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas—A two-center phase II trial (GBFiri)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14088-14088
Author(s):  
J. Feisthammel ◽  
K. Schoppmeyer ◽  
M. Wiedmann ◽  
J. Mossner ◽  
M. Schulze ◽  
...  
Keyword(s):  
Overall Survival ◽  
Folinic Acid ◽  
Biliary Tract ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Synergistic Activity ◽  
Biliary Cancer ◽  
Free Survival

14088 Background: The majority of patients with biliary tract cancer present with advanced, unresectable tumors. Irinotecan and 5-Fluorouracil/folinic acid (FOLFIRI) have synergistic activity in gastrointestinal cancers. The aim of this study was to determine the tolerability and activity of systemic chemotherapy with FOLFIRI in patients with intrahepatic cholangiocarcinoma (CCC) or gallbladder cancer (GBC). Methods: This was a prospective, multicenter, non-randomised, open-label, phase II trial. Eligibility criteria: Inoperable adenocarcinoma of the biliary tract, measurable disease, age 18–80 years, ECOG PS 0–2. Patients received irinotecan 80 mg/m2 as a 30 min infusion, followed by folinic acid 500 mg/m2 over 2 h and 5-FU 2000 mg/m2 over 24h weekly × 6 followed by a 2 week rest. Treatment was continued until progression or limiting toxicity. Response to therapy was assessed after every other cycle according to RECIST criteria. Primary end point was response rate, secondary end points were overall survival, progression free survival and toxicity. Results: 30 pts (CCC 17, GBC 13) were enrolled. A total of 387 doses (Median 12.9; 1 to 36) were administered with an overall relative dose intensity of 98%. 30 patients are evaluable for safety. WHO grade 3/4 drug related adverse events occured in 7 patients (23%): Leukopenias in 2, anemia in 1, and diarrhea in 4 patients. 14 patients completed 2 cycles and were evaluable for response. Response rates: CR 0/30, PR 3/30 (10%) and SD 3/30 (10%). 8 patients presented with disease progression at restaging. Median overall survival: CCC 166 days, GBC 327 days. Progression-free-survival: CCC 84 days, GBC 159 days. Conclusions: FOLFIRI is a well tolerated regimen in patients with biliary cancer that can be safely administered on an outpatient basis. FOLFIRI has no substantial activity in CCC and moderate activity in GBC. Further studies are required to define a standard palliative chemotherapy for treatment of biliary cancer. No significant financial relationships to disclose.

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