S304: PHASE II STUDY OF COMBRETASTATIN A4 PHOSPHATE(CA4P) IN PATIENTS WITH ADVANCED ANAPLASTIC THYROID CARCINOMA (ATC)
P.Savvides1, C.J.Mooney1, M.M.Cooney1,
S.S.Agarwala2, A.Dowlati1, J.Wasman1, D.Wang3, J.Ortiz1, P.Lavertu1,S.Remick4, 1Case Comprehensive Cancer Center, Cleveland, OH; 2St Luke’s Hospital and Health Network, Bethlehem, PA; 3Karmanos Cancer Institute, Detroit, MI; 4Mary Babb Randolph Cancer Center, Morgantown,WV
Background: CA4P is the first tubulin-binding vascular disrupting agent tested in the clinic, with demonstrable antitumor in vitro activity against anaplastic thyroid cancer (ATC) cell lines, xenografts, and demonstrable efficacy in a phase I trial. We now report the efficacy and safety results of the phase II trial. Methods: Patients with metastatic ATC, good performance status, normal ECG and cardiac function, and no prior therapy for disseminated disease were eligible for study. CA4P at a dose of 45 mg/m2 was administered as 10-minute IV infusion on days 1, 8 and 15 every 28 days (1 cycle) until progression of disease. Baseline serum soluble intracellular adhesion molecule-1 (sICAM) levels were obtained at baseline, over the first 2 cycles and end of therapy. Results: Overall, CA4P was well tolerated. Grade 3 and 4 toxicities were observed in 9 patients (35%) and one (4%), respectively. QTc prolongation was seen in 4 patients causing one to stop treatment. Overall median survival was 4.7 months with 34% alive at 6 months and 23% at 12 months. Baseline serum soluble intracellular adhesion molecule-1 (sICAM) levels were measured in 24 of the 26 patients with a median of 253.5 ng/ml (range 172.0 - 839.5). There was a highly significant difference in event free survival in patients with lower baseline sICAM levels (p = 0.013).
Conclusions: This is the largest prospective trial ever conducted for this rare disease. CA4P has an acceptable safety profile in the treatment of patients with advanced ATC. We were unable to demonstrate significant change in the natural history of ATC; onethird of patients survived more than 6 months, which is encouraging. Despite a small sample size, low baseline sICAM levels were predictive of event free survival. Further prospective validation of sICAM as a therapeutic biomarker and exploring combination regimens with CA4P are warranted.
[Supported in part by a clinical grant from OXiGENE, Inc., Waltham, MA and NIH grant nos. M01 RR-00080.]
I accept your rationale. A distinct possibility, but they will not be able to survive on their own much longer. They need a partner now, unless they ultimately agree to sell shares at $0.65 or even less.
That would totally destroy our asset base, but guarantee them another year or two of fat pay and glory. However, it will not compare well with what they could make on their unrealized options and shares now held. Therefore, a partner it is. Sooner or later, even these clowns will figure out that two and two still equals four.
"Management will hang on and try to keep control, because they like the unsupervised milking of this OXiGENE-cow. With a partnership deal, they lose control and have a boss. From time-spent to expenses-charged to the company, all will suddenly be scrutinized and checked.
The extra dilution will be neutralized for them with larger grants and more low-priced options. But keep in mind, Darius and Xerxes disappeared and so did Alexander the Great and Julius Caesar. Empire builders don't last. Oh, and the same fate is forecast for Citron, Chin and their cohorts."
but I disagree. Management (Chin et al) has a super ego and believe they know what's best for the company and of course, us. Such people just will never accept that they f'ed up. I've noticed that in politics too.
Well manof, the most important thing is of course to vote no to def14a. but of course it is a good thing to mark those you do not like aswell.
Just heard there are about 10k shareholders in Sweden. The ones with more shares than the rest is called up by some company employed to gather votes.
I have of course already voted no and a realist as I am I do not really think this vote will go against the BOD. IT would be a nice surprise though, to see owners really care about their rights and also recognize what Nasdaq has recognized. To see owners of a company disregard their rights as owners would be sad.
Mr ORacle wrote:
"But our vote is not really important; the company doesn't need our "YES-Vote" at this time."
That is exactly what they aim for. Everybody believing it is not important and then they will not vote.
Oracle your "savvy securities lawyer" should have told you the truth. The truth is that a NO vote is essential. That will force the management to ask shareholders for the coming dilutions. Then they will have to have a very goopd plan
WIth a non existant vot or a yes vote they get carte blanche to dilute without any idea whatsoever.
YOu have to vote NO! If you do not wish to give the company to managment fo course.
You assume a lot. Just because I didn't comment for some time on the issue, you think that I wasn't sure what to do. I never recommended a "YES-Vote" and always favored a "NO-Vote".
But our vote is not really important; the company doesn't need our "YES-Vote" at this time. Whatever the outcome, they will issue 5,900,000 new shares. The problem comes when they need to sell more shares in the fall, because 5,900,000 times $1.25 doesn't get them very far.
Management will hang on and try to keep control, because they like the unsupervised milking of this OXiGENE-cow. With a partnership deal, they lose control and have a boss. From time-spent to expenses-charged to the company, all will suddenly be scrutinized and checked.
The extra dilution will be neutralized for them with larger grants and more low-priced options. But keep in mind, Darius and Xerxes disappeared and so did Alexander the Great and Julius Caesar. Empire builders don't last. Oh, and the same fate is forecast for Citron, Chin and their cohorts.