The BERNIE study: A phase II study evaluating addition of bevacizumab (Bv) to chemotherapy in children and adolescents with metastatic rhabdomyosarcoma (mRMS) and non-rhabdomyosarcoma soft tissue sarcoma (mNRSTS).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS9597-TPS9597
Author(s):  
Julia C. Chisholm ◽  
Michela Casanova ◽  
Johannes H. Merks ◽  
Birgit Geoerger ◽  
Raphael F. Rousseau ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Combined Modality Therapy ◽  
Local Therapy ◽  
Long Term Effects ◽  
Induction Cycle ◽  
Weekly Cycles ◽  
To Receive

TPS9597^ Background: Despite therapeutic advances, patient outcomes in mRMS and mNRSTS remain poor. The phase I study (Glade-Bender et al., J Clin Oncol. 2008) indicated that Bv is well tolerated in children with refractory solid tumors and yielded pharmacokinetic (PK) data that support further studies of Bv in childhood cancer. Reports of Bv used in children with solid tumors showed safety profiles consistent with data from adults. Methods: In this phase II trial, 150 patients aged 6 months to 18 years who present with mRMS or mNRSTS are randomized to receive 18 months of standard combined modality therapy as per EpSSG guidelines, either alone or with Bv. Treatment consists of 2 phases: induction therapy [9 three-weekly cycles including 4 cycles of IVADo (ifosfamide, vincristine, actinomycin D, and doxorubicin), followed by 5 cycles of IVA (i.e., without doxorubicin)] and maintenance therapy (12 four-weekly cycles of vinorelbine and cyclophosphamide). Local therapy is considered after the 6th induction cycle. Primary endpoint is event-free survival (EFS). PK sampling is performed on all patients randomized to the experimental arm during the first 4 cycles of induction. After the primary efficacy and safety analysis, all patients who have not met the primary endpoint are followed for at least 47 months for survival and long-term effects of treatment. The study enrolled 75 patients between July 2008 and January 2012; 37 patients discontinued study treatment (including 17 patients who died, all due to disease progression) and 9 patients have completed study treatment.

Radiation ±cisplatin for bulky stage IB cervical carcinoma; Long-term follow-up of a GOG trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5015-5015
Author(s):  
F. B. Stehman ◽  
S. Ali ◽  
D. G. Gallup ◽  
H. Key
Keyword(s):  
Cervical Carcinoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Ib ◽  
Long Term Follow Up ◽  
Weekly Cycles ◽  
To Receive ◽  
Weekly Cisplatin

5015 Purpose: To confirm that concurrent cisplatin (CT) with radiation (RT) is associated with improved long-term progression-free survival (PFS), overall survival (OS), and decreased morbidity compared to RT stage IB bulky carcinoma of the cervix, when both groups’ therapy is followed by hysterectomy. Methods: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 40 Gray (Gy) in 20 fractions followed by a single low dose-rate intracavitary application of 30 Gy to Point A. Chemotherapy consisted of cisplatin 40 mg/M2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 3–6 weeks. Results: Preliminary results have been published, at which time there many censored observations and limited follow-up. Patient and tumor characteristics were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43–0.85, p < 0.004). At 72 months 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43–0.91, p < 0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events. Conclusion: Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens must be compared. Key Words: Cervical carcinoma, chemoradiotherapy. No significant financial relationships to disclose.

SAPPHIRE: A randomized phase II study of mFOLFOX6 + panitumumab versus 5-FU/LV + panitumumab after 6 cycles of frontline mFOLFOX6 + panitumumab in patients with colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 729-729 ◽  
Author(s):  
Masato Nakamura ◽  
Yoshinori Munemoto ◽  
Masazumi Takahashi ◽  
Masahito Kotaka ◽  
Hiroaki Kuroda ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Wild Type ◽  
Primary Analysis ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Term Administration ◽  
To Receive ◽  
Clinical Trial Information

729 Background: FOLFOX therapy, an infusion of 5-fluorouracil (5-FU) with leucovorin in combination with oxaliplatin (OXA), is a common first-line chemotherapy regimen for unresectable, advanced or recurrent colorectal carcinoma (CRC). However, long-term administration of OXA is associated with peripheral neuropathy (PN); decreasing treatment length of OXA may be beneficial without reducing its efficacy. Methods: Chemotherapy-naïve pts aged ≥20 yrs with RAS wild-type advanced/recurrent CRC were enrolled to receive 6 cycles of panitumumab (Pmab) + mFOLFOX6 once every 2 wks. Pts who completed 6 cycles of Pmab + mFOLFOX6 and confirmed no progressive disease were subsequently randomized 1:1 to continue to receive Pmab + mFOLFOX6 (arm 1) or Pmab + 5-FU/LV (arm 2). The primary endpoint was progression-free survival (PFS) rate at 9 mos after randomization. The threshold PFS rate was defined as 30%, and the expected rate was set at 50%, with a 90% power and a 1-sided alpha value of 0.10. In the primary analysis, a binomial test was conducted separately for each arm. This study was designed as a phase II randomized screening comparison study which does not use direct comparison for the primary analysis. Results: Of 164 enrolled pts who received initial Pmab + mFOLFOX6 treatment, 56 were randomized to arm 1 and 57 to arm 2. PFS rates at 9 mos after randomization were significantly higher than the defined threshold at 44.6% (80% CI, 36.4–53.2) in arm 1 and 47.4% (39.1–55.8) in arm 2. Median PFS after randomization was 9.1 (8.6–11.2) and 9.3 (6.0–13.0) mos, respectively. Grade ≥2 PNs occurred in 6 (10.7%) and 1 (1.8%) pts in arms 1 and 2, respectively. Serious AEs occurred in 14 (25.0%) pts in arm 1 and in 9 (16.7%) pts in arm 2. Conclusions: The results of this trial suggest that Pmab + 5-FU/LV after 6 fixed-cycles of Pmab + mFOLFOX6 may be a treatment option in pts with RAS wild type chemotherapy-naïve advanced/recurrent CRC. Pts treated with Pmab + 5-FU/LV had a lower occurrence of grade ≥2 PNs compared with Pmab + mFOLFOX6. Clinical trial information: NCT02337946.

A phase II study of MEK162 (binimetinib [BINI]) in combination with imatinib in patients with untreated advanced gastrointestinal stromal tumor (GIST).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11508-11508
Author(s):  
Ping Chi ◽  
Li-Xuan Qin ◽  
Ciara Marie Kelly ◽  
Sandra P. D'Angelo ◽  
Mark Andrew Dickson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Objective Response ◽  
Type I ◽  
Combination Strategy ◽  
Primary Resistance ◽  
Long Term Treatment ◽  
Advanced Gist

11508 Background: ETV1 and KIT are lineage-specific master transcriptional and signaling survival factors in GIST. In preclinical models, dual lineage targeting of ETV1 by MEK inhibition with BINI and KIT by imatinib are synergistic in suppressing GIST tumorigenesis and progression. This single-arm phase II study is designed to test the efficacy of the BINI+imatinib as a first-line treatment in patients (pts) with advanced GIST. Methods: Adult pts with untreated advanced GIST received imatinib (400mg daily) plus BINI (30mg twice daily), 28-day cycles. The primary endpoint (EP) was RECIST1.1 objective response rate (ORR) (complete response [CR]+partial response [PR]). The study was designed to detect a 20% improvement in the ORR of imatinib alone (unacceptable rate of 45%; acceptable rate of 65%). A sample size of 44 patients was required, using an exact binomial test, one-sided type I error of 0.08 and type II error of 0.1. Confirmed PR in > 24 pts would be considered positive. Secondary EPs included RR by Choi and EORTC criteria, resectability conversion rate (RCR), progression free survival (PFS), overall survival (OS) and long-term AEs. Correlatives included characterization of tumor genomics by MSK-IMPACT, cfDNA by MSK-ACCESS, ETV1 protein levels and transcriptomes and signaling inhibition. Results: At data cutoff of Jan 31, 2020, 38/39 pts with advanced GIST of all genotypes, including 3 KIT/PDGFRA-wild type GIST pts, were evaluable for primary EP. Median age 60 (range 29-78), 29% female. 26/38 pts with confirmed PR; Best ORR was 68.4% (two-sided 95% CI, 51-83%; one-sided 90% CI, 57-100%). 8/9 pts became resectable after treatment; RCR was 88.9% (95% CI, 52-100%). 13 pts remain on trial (2-159 weeks [wks]). 9 pts discontinued trial due to disease progression (11-159 wks); one pt progressed within 3 months, indicating primary resistance. Grade 3/4 toxicity included CPK elevation (asymptomatic, 61%), neutrophil decrease (11%), maculopapular rash (8%), anemia (8%). No unexpected toxicities observed. Correlation of outcome with MSK-IMPACT, MSK-Access and paired tumor biopsies will be presented. Conclusions: This study met its primary endpoint. BINI plus imatinib is highly effective in treatment-naive advanced GIST, with expected and manageable long-term treatment-associated toxicities. The combination strategy warrants further evaluation in direct comparison with imatinib in the frontline treatment of GIST. Clinical trial information: NCT01991379 .

Space-exposed seed experiment developed for students

1992 ◽  
Vol 50 (1) ◽  
pp. 860-861
Author(s):  
Donna Leeper ◽  
Kelvin Bridgers ◽  
Ernest C. Hammond
Keyword(s):  
The United States ◽  
Test Results ◽  
Long Term Effects ◽  
The Earth ◽  
Long Duration ◽  
Foreign Countries ◽  
Abundant Supply ◽  
Germination And Growth ◽  
To Receive

The SEEDS project was flown in orbit aboard the Long Duration Exposure (LDEF) for nearly six years. During this time in space, the tomato seeds received an enormously abundant supply of cosmic radiation. Upon the return of the LDEF to earth, the SEEDS project was distributed throughout the United States and 30 foreign countries for analysis. The purpose of the experiment was to determine the long term effects of cosmic rays on living tissue. At Morgan, the analysis performed varied from germination and growth rates to electron microscopy and x ray analysis.In analyzing the seeds under the electron microscope, usual observations were performed on the nutritional and epidermic layers of the seed. These layers appeared to be more porous in the space-exposed seeds than in the Earth-based control seeds. This unusual characteristic may explain the increase in the space seeds’ growth pattern. (Several test results show that the space-exposed seeds germinate sooner than the Earth-based seeds. Also, the space exposed seeds are growing at a faster rate.) The porous nutritional region may allow the the seeds to receive necessary nutrients and liquids more readily. Thus, enabling the plant to grow at a much faster rate.

A randomized phase II/III study of naptumomab estafenatox plus IFN-α versus IFN-α in advanced renal cell carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3073-3073 ◽  
Author(s):  
Robert E. Hawkins ◽  
Martin Eric Gore ◽  
Yaroslav Shparyk ◽  
Vladimir Bondar ◽  
Oleg Gladkov ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase 1 ◽  
Risk Scores ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
To Receive

3073 Background: Naptumomab estafenatox/ANYARA (Nap) is a fusion protein of an antibody (5T4) and a superantigen (SEA/E-120). After phase I studies (Borghaei. J Clin Oncol. 2009, 27:4116) a prospective, randomized phase II/III trial of Nap + IFN-α (A) vs IFN-α (I) was conducted. Methods: Patients (pts) with RCC were randomized in an open label study to receive A or I. The primary endpoint was OS. Secondary endpoints were PFS, response rate and safety. Baseline (bl) plasma IL-6 was predictive of pazopanib (Tran. Lancet Oncol. 2012, 13:827) and MVA-5T4 vaccine (Harrop. Cancer Immunol Immunother. 2012, 61:2283) benefit in RCC pts. IL-6 and anti-SEA/E-120 antibodies (a-S) were analyzed. A subgroup SG1 had bl levels below median for IL-6 (<7 pg/ml) and a-S. Another subgroup SG2 had IL-6 below 13 pg/ml (Tran. Lancet Oncol. 2012, 13:827) and excluding upper quartile of a-S according to phase 1 levels (Borghaei. J Clin Oncol. 2009, 27:4116). Results: From 5/2007 to 10/2010 513 pts were treated (ITT) with a median follow-up time for censored pts of 43 months. Unexpectedly, pts in certain territories had increased bl a-S (median of 61 pmol/ml in Russia vs 34 in UK). The table summarizes efficacy results. The primary endpoint was not met. Multivariate analysis adjusted for risk scores and subsequent TKI usage verified Nap benefit in pts with low IL-6 and normal a-S. Nap was well tolerated. Pyrexia (A:46%/I:18%), nausea (21%/11%), back pain (18%/6%), vomiting (16%/7%) and chills (12%/4%) were more common after Nap. Conclusions: The study did not meet primary endpoint. In pts with low IL-6 and normal levels of a-S, addition of Nap to IFN-α improves OS and PFS. The results warrant further studies with Nap in sequence or combo with e.g. TKIs in this subgroup. More generally, as bl IL-6 appears to be prognostic and predictive of outcome on treatment with TKIs and immunotherapies this may be a stratification factor for RCC studies. Clinical trial information: NCT00420888. [Table: see text]

A randomized phase II/III trial of conventional paclitaxel and carboplatin with/without bevacizumab versus dose-dense paclitaxel and carboplatin with/without bevacizumab, in stage IVB, recurrent, or persistent cervical carcinoma (JCOG1311): Results of the phase II part.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6027-6027
Author(s):  
Mitsuya Ishikawa ◽  
Ryo Kitagawa ◽  
Taro Shibata ◽  
Hideki Tokunaga ◽  
Takashi Iwata ◽  
...  
Keyword(s):  
Cervical Carcinoma ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Local Therapy ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Primary Analysis ◽  
Dose Dense

6027 Background: A randomized controlled trial was conducted to assess the efficacy and safety of dose-dense, weekly paclitaxel plus carboplatin (ddTC) with or without bevacizumab (Bmab) compared to conventional, tri-weekly paclitaxel plus carboplatin (cTC) with or without Bmab, in metastatic or recurrent cervical carcinoma not amenable to curative treatments with local therapy. Methods: Patients were randomly assigned to either a cTC or a ddTC regimen. After Bmab was approved in Japan (in May 2016) the protocol was amended, and patients on both arms received Bmab if not contraindicated. The cTC was paclitaxel 175 mg/m2 intravenously (IV) for 3 h on day 1 followed by carboplatin at an area under the curve of five IV for 1 h on day 1. The ddTC was paclitaxel 80 mg/m2 IV for 1 h on day 1 followed by carboplatin at an area under the curve of five IV for 1 h on day 1 and paclitaxel 80 mg/m2 IV for 1 h on day 8 and day 15. Both cTC and ddTC treatments were repeated every three weeks, for up to nine cycles. Bmab 15 mg/kg IV was repeated until progression or unacceptable toxicity. The primary endpoint of phase II was the response rate (RR) in patients with measurable lesion, who had received Bmab. If the RR of the ddTC + Bmab arm was greater than that of the cTC + Bmab arm for more than 5%, the study would proceed to phase III, which had overall survival (OS) as its primary endpoint. The planned sample size in the phase II part was 56 to select the ddTC arm with a probability of at least 75% if the difference of RR was 15% or more (45% vs. 60%). Results: Patient accrual started in October 2015. It was suspended in May 2019 because the number of Bmab-treated patients with measurable lesions reached 56. In total, 122 patients were enrolled and randomly assigned to either the cTC arm (cTC: 29 patients; cTC + Bmab: 32 patients) or the ddTC arm (ddTC: 30 patients; ddTC + Bmab: 31 patients). The primary analysis of the phase II part was conducted in November 2019. The RRs of each regimen were 67.9% [95% CI, 47.7-84.1] (19/28, cTC + Bmab), 60.7% [40.6-78.5] (17/28, ddTC + Bmab), 55.2% [35.7-73.6] (16/29, cTC), and 50.0% [29.9-70.1] (13/26, ddTC). Conclusions: The study did not meet the primary endpoint of phase II. Dose-dense, weekly paclitaxel plus carboplatin is not promising for metastatic or recurrent cervical carcinoma. Clinical trial information: jRCTs031180007.

Sign in / Sign up

Export Citation Format

Share Document