Phase II diaziquone-based chemotherapy trials in patients with anaplastic supratentorial astrocytic neoplasms.

1987 ◽  
Vol 5 (3) ◽  
pp. 464-471 ◽  
Author(s):  
S C Schold ◽  
M S Mahaley ◽  
N A Vick ◽  
H S Friedman ◽  
P C Burger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Important Distinction ◽  
Histologic Diagnosis ◽  
Anaplastic Gliomas ◽  
Phase Iii Trials ◽  
Survival Differences ◽  
Astrocytic Neoplasms

We treated 103 patients with histologically confirmed anaplastic supratentorial astrocytic neoplasms with either diaziquone (AZQ) and carmustine (BCNU) or AZQ and procarbazine. There were 74 patients with glioblastoma multiforme (GBM) and 29 patients with anaplastic astrocytoma (AA). AZQ plus BCNU produced partial (PR) or unequivocal responses in seven of 32 (21.9%) patients with GBMs and three of ten (30%) patients with AAs. Two patients with GBMs (6.3%) and five patients with AAs (50%) showed stable disease (SD). AZQ plus procarbazine produced PRs or unequivocal responses in five of 42 (11.9%) patients with GBMs and nine of 19 (47.4%) patients with AAs. Eight patients with GBMs (19%) and one patient with an AA (5.2%) showed SD. In addition to histologic diagnosis, only the Karnofsky performance-status (KPS) rating independently influenced response and survival. Differences in response rates between the two regimens were not significant, although estimated median survival after adjusting for performance status was slightly better with AZQ plus BCNU than with AZQ plus procarbazine (P = .031). Neither age nor prior chemotherapy were significant independent risk factors. Toxicity was mild and primarily hematologic. We conclude that these AZQ-based regimens have activity in patients with recurrent anaplastic gliomas, but that they are not clearly superior to other agents in current use. The histologic diagnosis of GBM is associated with a significantly worse prognosis than AA, and we believe that this important distinction must be recognized in phase II as well as phase III trials.

Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

2006 ◽  
Vol 24 (4) ◽  
pp. 663-667 ◽  
Author(s):  
Jaffer A. Ajani ◽  
Fa-Chyi Lee ◽  
Deepti A. Singh ◽  
Daniel G. Haller ◽  
Heinz-Josef Lenz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Median Number ◽  
Phase Iii ◽  
Highly Active ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastric Cancer Patients

Purpose S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination. Methods Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of ≥ 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed. Results All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death. Conclusion S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer

2016 ◽  
Vol 34 (22) ◽  
pp. 2636-2643 ◽  
Author(s):  
Cora Sternberg ◽  
Andrew Armstrong ◽  
Roberto Pili ◽  
Siobhan Ng ◽  
Robert Huddart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Point ◽  
Castration Resistant ◽  
Phase Iii Study

Purpose Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

A nomogram predicting survival of patients (pts) with metastatic or unresectable urothelial cancer (UC) treated with cisplatin-based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5055-5055 ◽  
Author(s):  
D. F. Bajorin ◽  
I. Ostrovnaya ◽  
A. Iasonos ◽  
M. I. Milowsky ◽  
M. Boyle ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Cox Model ◽  
Performance Status ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Long Term Outcome ◽  
Phase Ii Studies ◽  
Phase Iii Trials ◽  
Pre Treatment

5055 Background: Cisplatin-based chemotherapy is the standard of care for pts with metastatic or unresectable UC with phase III studies reporting median survivals of 12–15 months. Even more survival variation exists in phase II studies and this disparity is most frequently due to prognostic factors and not individual regimens. Thus, better tools are needed to predict survival both for individual pts and to balance phase III trials. Nomograms have utility in predicting short- and long-term outcome in muscle-invasive UC treated by surgery but they have not been explored in more advanced UC. Methods: We identified 308 pts with metastatic and/or unresectable UC treated on prospective phase II MSKCC protocols of cisplatin-based therapy containing 3–5 total chemotherapy agents. 203 pts received methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), 45 had ifosfamide, paclitaxel and cisplatin (ITP) and 60 pts received doxorubicin plus gemcitabine (AG) followed by ITP (AG-ITP). Survival distributions were compared across trials. Pre-treatment characteristics were then assessed for impact on survival and a nomogram from a fitted Cox model was created to predict 1-yr, 2-yr, 5-yr and median survival. Results: No difference in median survivals were seen among the 3 regimens; median survival was 14.8 months for MVAC, 18.0 months for ITP and 16.1 months for AG- ITP (p=NS). Median survival for all pts was 12.99 months; 268 pts died and 40 pts were censored. 288 pts had all pre-treatment data. Characteristics most associated with survival included visceral metastases (present versus absent, p=.00001) and Karnofsky poor performance status (≥ 80 versus < 80, p= .0005) followed by hemoglobin (normal versus < normal, p=.01) and albumin (actual values, p<.02). These characteristics were then used to construct a nomogram utilizing all 4 factors to predict probabilities of 1-yr, 2-yr, and 5-yr survival. Conclusions: The number and sequence of drugs utilized in cisplatin-based chemotherapy did not substantially impact survival of pts with advanced UC. A nomogram of pre-treatment clinical factors can predict probability of pt survival at 1 yr, 2yrs, and 5 yrs. This nomogram may also be useful to balance treatment arms in phase III trials. No significant financial relationships to disclose.

Randomized phase II trial of irinotecan plus cisplatin (IP) versus irinotecan, cisplatin plus etoposide (IPE) every three weeks in patients with extensive disease small cell lung cancer (ED-SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7087-7087
Author(s):  
I. Sekine ◽  
H. Nokihara ◽  
K. Takeda ◽  
Y. Nishiwaki ◽  
K. Nakagawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Body Weight Loss ◽  
Complete Response ◽  
Phase Iii ◽  
Antitumor Effects ◽  
Pilot Studies ◽  
Randomized Phase Ii ◽  
Phase Iii Trials ◽  
Grade 3

7087 Background: A promising complete response rate and median survival time were obtained in our previous phase II study of IPE chemotherapy repeated every 4 weeks in patients with ED-SCLC, but the infusion of irinotecan on day 15 was omitted in 77% of patients. Methods: The objective was to evaluate toxicities and antitumor effects of IP and IPE regimens every 3 weeks and to select the arm for subsequent phase III trials. The primary endpoint was overall survival. Previously untreated ED-SCLC patients aged between 20 and 70 years old with a performance status (PS) of 0–2 were randomized to receive either IP (I 60 mg/m2 days 1, 8 and P 60 mg/m2 day 1) or IPE (the same dose of IP and E 50 mg/m2 days 1–3 with G-CSF support) every 3 weeks for 4 cycles. The projected sample size was 110 patients (Liu’s Selection design for pilot studies on survival). Results: From March 2003 to May 2005, 53 patients (43 males/10 females, median age 63) were randomized to IP and 57 patients (48 males/9 females, median age 62) to IPE. Body weight loss and PS were well balanced between the arms. Full cycles were administered in 75% of patients in the IP and in 67% in the IPE arm. Dose reduction was required in 17% of patients in the IP and 28% in the IPE arm. Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 53%, 34% and 4% of patients in the IP, and 93%, 45%, and 23% of patients in the IPE arm, respectively. Grade 3–4 infection, malaise, anorexia, and diarrhea were noted in 15%, 2%, 0%, and 15% of patients in the IP, and 30%, 11%, 15%, and 24% of patients in the IPE arm, respectively. No treatment related death occurred. Complete and partial responses were noted in 8% and 68% of patients in the IP, and 11% and 75% of patients in the IPE arm, respectively. Conclusion: Toxicity was more severe, but tumor responses seemed better in the IPE arm. The survival analysis will be carried out in April 2006. No significant financial relationships to disclose.

A phase II study of Chinese patients (pts) treated with nab-paclitaxel (nab-P) plus gemcitabine (Gem) for metastatic pancreatic cancer (MPC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 327-327 ◽  
Author(s):  
Lin Shen ◽  
Xianjun Yu ◽  
Jihui Hao ◽  
Liwei Wang ◽  
Hongming Pan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3 ◽  
Stage 1

327 Background: nab-P + Gem demonstrated significantly better overall survival (OS; median: 8.7 vs 6.6 mo; HR 0.72; P < 0.001) than Gem alone as first-line treatment for pts with MPC in the MPACT study. This phase II bridging study evaluated efficacy and safety of nab-P + Gem in Chinese pts with MPC. Methods: Efficacy and safety of nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 every 4 weeks was evaluated in a 3-part sequential study. In part 1, safety was examined. In part 2, efficacy was evaluated by the Simon optimal 2-stage design. If there were > 2 responses in 28 pts in stage 1 of part 2, an additional 54 pts would be treated in stage 2. The study would be completed if > 9 responses were observed. If there was an insufficient number of responses in either stage of part 2, part 3 would be triggered to compare nab-P + Gem vs Gem alone. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), OS, and safety. Correlation of OS and baseline neutrophil-to-lymphocyte ratio (NLR) was also analyzed. Results: Eighty-three pts were treated. Median age was 57.0 y; 19% were aged > 65 y; baseline Karnofsky performance status was 90 - 100 in 70% of pts and 70 - 80 in 30%. Combining results for stages 1 and 2, ORR was 35% by independent assessment, median DOR was 8.9 mo (95% CI, 6.01 - 8.94), median OS and PFS were 9.2 mo (95% CI, 7.60 - 11.10) and 5.5 mo (95% CI, 5.29 - 7.16), respectively (Table). Baseline NLR ≤ 5 was associated with a nonsignificant trend toward longer OS vs NLR > 5 (median, 10.0 vs 8.3 mo; HR 0.62; P= 0.148). The most common grade ≥ 3 adverse events included neutropenia (37%), leukopenia (31%), and fatigue (14%). Grade ≥ 3 peripheral neuropathy occurred in 7% of pts. Part 3 was not triggered per study design. Conclusions: nab-P + Gem demonstrated efficacy in Chinese pts with MPC. The OS and ORR were numerically better than those of the phase III MPACT trial (Table). A trend toward longer OS in pts with baseline NLR ≤ 5 vs > 5 confirmed previous findings from the MPACT study. No new safety signals were identified. Clinical trial information: NCT02135822. [Table: see text]

Biofeedback

2016 ◽  
Vol 4 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Paul Lehrer
Keyword(s):  
Phase Ii ◽  
Real Life ◽  
Phase Iii ◽  
Controlled Trials ◽  
Clinical Environment ◽  
Phase Ii Trials ◽  
Research Support ◽  
Phase Iii Trials ◽  
Psychosomatic Problems ◽  
Biofeedback Research

Although evidence supports the efficacy of biofeedback for treating a number of disorders and for enhancing performance, significant barriers block both needed research and payer support for this method. Biofeedback has demonstrated effects in changing psychophysiological substrates of various emotional, physical, and psychosomatic problems, but payers are reluctant to reimburse for biofeedback services. A considerable amount of biofeedback research is in the form of relatively small well-controlled trials (Phase II trials). This article argues for greater payer support and research support for larger trials in the “real life” clinical environment (Phase III trials) and meta-analytic reviews.

Randomized phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6015-6015
Author(s):  
Julie E. Bauman ◽  
Nabil F. Saba ◽  
Denise Roe ◽  
Jessica R. Bauman ◽  
John M. Kaczmar ◽  
...  
Keyword(s):  
Lower Bound ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Primary Objective ◽  
Phase Iii ◽  
Platinum Resistance ◽  
Eligibility Criteria ◽  
Immune Biomarkers ◽  
Hpv Status

6015 Background: Cetuximab (C), an anti-EGFR monoclonal antibody (mAb), is approved for advanced HNSCC but benefits a minority. Crosstalk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways is a known resistance mechanism. HGF is also immunosuppressive within the tumor microenvironment. A Phase I study confirmed the safety of C and ficlatuzumab (F), an IgG1 anti-HGF mAb, with preliminary efficacy and biomarker data suggesting that dual pathway inhibition may overcome tumor-intrinsic or immune cetuximab resistance. Methods: The primary objective of this phase II randomized, non-comparative trial was to evaluate the efficacy of F (20 mg/kg every 2 wks), with or without C (500 mg/m2 every 2 wks), in pan-refractory, advanced HNSCC. Eligibility criteria included recurrent/metastatic HNSCC, performance status (PS) 0-1, C resistance (defined as progression on or within 6 months of exposure), and resistance to or ineligibility for platinum and anti-PD1 mAb. Randomization was stratified by HPV status and center. The primary endpoint was median progression-free survival (mPFS). An arm was deemed worthy of further study if the lower bound of the 90% 1-sided confidence interval (CI) excluded the historical control of 2 months. Secondary objectives included overall response rate (ORR) in the overall and HPV-stratified populations. A Bayesian continuous monitoring rule for futility was applied. Results: 60 patients were randomized and 58 treated between Jan 2018 and Dec 2020 (27 to F; 33 to FC). Baseline characteristics were balanced across major prognostic variables including age, PS, HPV status, platinum resistance, and PD1 mAb exposure. Median time since prior cetuximab was 3.5 months (range 0-48 months). Grade ≥3 adverse events attributed to F included: pneumonitis (2); edema (3); diarrhea (1); LFT elevation (1); rash (2); electrolyte abnormality (2). The Table presents efficacy data. The F arm stopped for futility after 26 evaluable subjects accrued. The FC arm completed accrual and met the primary endpoint; 32 evaluable subjects had mPFS of 3.6 months (lower bound 90% 1-sided CI: 2.3 months) and ORR of 19% (6/32). All responses were in HPV- subjects, including 2 complete (CR) and 4 partial responses (PR) to the FC combination and 1 PR to F monotherapy. The mPFS and ORR for the HPV- population (n = 16) on FC were 3.8 months and 38% (6/16). Mechanistic signaling and immune biomarkers are under analysis. Conclusions: The well-tolerated FC combination met the primary PFS endpoint in pan-refractory, advanced HNSCC with notable activity in HPV- HNSCC, warranting phase III investigation. Clinical trial information: NCT03422536. [Table: see text]

scholarly journals P14.120 Phase II study of weekly carboplatin in pretreated adult malignant gliomas

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii97-iii97
Author(s):  
V Villani ◽  
A Pace ◽  
A Vidiri ◽  
A Tanzilli ◽  
F Sperati ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Malignant Gliomas ◽  
Recurrent Malignant Glioma ◽  
Eligibility Criteria

Abstract BACKGROUND Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas MATERIAL AND METHODS This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) > 60. RESULTS Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p>0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit. CONCLUSION Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma

scholarly journals Targeting Angiogenesis in Prostate Cancer

2019 ◽  
Vol 20 (11) ◽  
pp. 2676 ◽  
Author(s):  
Zsombor Melegh ◽  
Sebastian Oltean
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Iii ◽  
Refractory Disease ◽  
Phase Ii Trials ◽  
Angiogenic Activity ◽  
Angiogenic Therapy ◽  
Resistant Refractory ◽  
Castration Resistant ◽  
Phase Iii Trials

Prostate cancer is the most commonly diagnosed cancer among men in the Western world. Although localized disease can be effectively treated with established surgical and radiopharmaceutical treatments options, the prognosis of castration-resistant advanced prostate cancer is still disappointing. The objective of this study was to review the role of angiogenesis in prostate cancer and to investigate the effectiveness of anti-angiogenic therapies. A literature search of clinical trials testing the efficacy of anti-angiogenic therapy in prostate cancer was performed using Pubmed. Surrogate markers of angiogenic activity (microvessel density and vascular endothelial growth factor A (VEGF-A) expression) were found to be associated with tumor grade, metastasis, and prognosis. Six randomizedstudies were included in this review: two phase II trials on localized and hormone-sensitive disease (n = 60 and 99 patients) and four phase III trials on castration-resistant refractory disease (n = 873 to 1224 patients). Although the phase II trials showed improved relapse-free survival and stabilisation of the disease, the phase III trials found increased toxicity and no significant improvement in overall survival. Although angiogenesis appears to have an important role in prostate cancer, the results of anti-angiogenic therapy in castration-resistant refractory disease have hitherto been disappointing. There are various possible explanations for this lack of efficacy in castration-resistant refractory disease: redundancy of angiogenic pathways, molecular heterogeneity of the disease, loss of tumor suppressor protein phosphatase and tensin homolog (PTEN) expression as well as various VEGF-A splicing isoforms with pro- and anti-angiogenic activity. A better understanding of the molecular mechanisms of angiogenesis may help to develop effective anti-angiogenic therapy in prostate cancer.

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