ALB 109564 - stability ASPS > 1 year

[Fictional]

Thought I'd open up a new thread. If this stuff was available to us, we would try it, but we're not eligible because minimum age is 18.

The trial is here: http://clinicaltrials.gov/ct2/show/NCT00724100

I spoke to Dr. Christine Anderson: 713-353-7911

There was a 32 year old woman (primary in the buttock) who looked gravely ill ("thought she may be a candidate for hospice") and was actively progressing at time of entry. She did well on the drug (infusion every 3 weeks) and now is back to playing soccer and has set a goal for herself of 200 situps at day, full time at work.

I don't know about tumor shrinkage - I think it is mostly stability - but stability is not bad if the stem cells are killed. The more I think about some of the long-term survivors with ASPS, the more I don't think it's so bad if the tumors don't go away - but it is best if they are not growing at all.

The benefit of this drug is especially interesting because some of the long survivors in this drug have had an earlier vinca drug as part of their regimen (Amanda Minderlein for instance...and maybe Camilla?). This drug looks like very low side effects.

The drugs such as Cediranib and Sutent still have the greatest track record for ASPS and definitely the most highly recommended for 'bulky' and multiple site disease, but it is nice if there can be something else added to ones regimen if one stops a VEGF inhibitor type drug. The thing that is a bit nerve wracking about anti-angiogenesis inhibitors is that they are not so easy to start and stop for surgeries or procedures like ablataion. You can do it, but disease may rebound when you're off the drug. The TKIs block the receptor, but blood VEGF levels may actually rise while you're on the drug. As a result, when you stop the receptor inhibitor, disease can grow very fast. Having more drugs in the arsenal will be important I think, but we don't know what the best drugs are to switch on or off. Maybe I will brood about this TKI issue on the TKI thread (I never know where to put posts). My brain does not work in individual 'threads'. Anyway although I do not know whether this drug (the ALB) is good for advanced or bulky disease, it is promising and we'll look forward to seeing if more people have responses. What we like about it is the very low side effect profile (makes sense in general with these drugs) and the fact it has been working at least in this one gal.

http://abstract.asco.org/AbstView_74_41250.html

Abstract:

Background: ALB 109564(a) [ALB] is a vinca alkaloid, which functions as a tubulin inhibitor, interfering with microtubule polymerization resulting in metaphase arrest. In preclinical studies, ALB was active in a wide variety of tumor types (e.g., colon, NSCLC, prostate) at concentrations comparable to those of approved vinca alkaloids. Methods: This study sought to determine the maximum tolerated dose based upon first cycle toxicity in 3-6 patients at each dose level, as well as to evaluate the pharmacokinetics of ALB when administered intravenously every three weeks. The starting dose was 1.2 mg/m2, and escalation proceeded according to a modified Fibonacci scheme. Results: 28 patients have been administered ALB across eight dose levels (1.2 to 12 mg/m2). No dose-limiting toxicities as well as no serious adverse events specifically attributed to ALB were observed. Through seven cohorts, adverse events reported to be at least possibly related to study drug were constipation (n=5), anemia (n=2), fatigue (n=2), blurred vision (n=1), decreased appetite (n=1), flushing (n=1), paresthesia (n=1), and rash (n=1); all were either grade 1 or 2. The overall half-life of ALB was 19.05 ± 8.80 hours, which is comparable to that of approved vinca alkaloids. Of 21 patients evaluable for clinical activity, one alveolar small part sarcoma patient, who had marked progression prior to enrollment, has received 21+ cycles of study drug with stable disease. An additional four patients have had stable disease after two or more cycles; one anal (7+ cycles), one pancreatic (5+ cycles), one colon (4 cycles), and one NSCLC (4 cycles). Conclusions: ALB is well tolerated and has shown preliminary activity in disease types not typically associated with approved vinca alkaloids. Further trials in soft tissue sarcoma are in development.

[Olga]

'F', that's a good call, we will have to watch for this ALB drug progression trough the trials.
I also am interested in this situation you noted "The TKIs block the receptor, but blood VEGF levels may actually rise while you're on the drug", I have read about it and this is one of the reasons that I would be glad to hear after the completion of the trial at the NCI if the efficacy of the cediranib is linear in proportion to its dose or it is still effective at the lower doses as probably at the lower doses it causes less resistant rising of the VEGF. I am having the similar issue with my anti migraine med sumatriptan as it blocks the appropriate receptor fine but the blood levels of the serotonin seems to increase as the body registers its lack and increases the signal demanding for it so hence the rebound migraine, so I am trying to combat it by using the minimal dosage that still works in hope to cause less rebound increase. I would really like them at the NCI to look into the minimal dose of the cediranib that still works, I am not sure if they will do that though.

[Fictional]

I forgot to add that the email contact for Dr. Anderson is: christineanderson@westat.com
She gets back to you fairly quickly. She is a nice person.

Also, although she said no to us now for an age waiver, she didn't eliminate the possibility - if they have more experience with the drug after a few months, they may reconsider an age waiver (letting us in because 'K' is younger than age 18). We're on another trial drug now anyway.

She told us that we could be back in touch with her in September.

[Arch]

Here's a quick update -
The ASPS patient on this trial is still stable now after 31 cycles of ALB 109564, which is very encouraging. However, there are no other ASPS patients on this trial yet.

[Fictional]

This is awesome news. Thanks, Arch.

Their cycles are only 3 weeks I think, but that still means almost 2 years.

Rolle wants to do Kgal's right side whenever we leave our current study and then she can have cryo on the left. Maybe after doing all this and we're looking for another study, we might be able to get into this one.

What I liked about ALB so much is that it was such low toxicity. The practical difficulty is that it's only in Boston.

[Olga]

This trial is also now recruiting here:

United States, New York
Montefiore-Einstein Cancer Center
Bronx, New York, United States, 10461
Contact: Mohammed Ghalib, MD 718-405-8515 mhghalib@montefiore.org
Contact: Imran Chaudhary 718-405-8542 ichaudha@montefiore.org
Principal Investigator: Sridhar Mani, MD

[Arch]

Update - When I contacted them about a month ago, I was told that they are not taking in any more patients. The clinicalTrails.gov site says that the trial has been suspended.