XL-184 (Cabozantinib) Plus Docetaxel Clinical Trial (NCT01683994)

I have not had much time to post here lately, but thought I'd share my experience on the trial combining Docetaxel (chemo) w/prednisone and XL-184 (cabozantinib). This initial post is long, but I assure you the periodic updates will not be so. It's just one persons experience...

Brief recap for new members:
I was diagnosed approx. 18 months ago. PSA was 84, G9 (12/12 cores positive), lymph nodes and bone mets (hips, ribs, spine). Had a great response to HT (Lupron/Casodex) and reached a PSA nadir of 0.2 approx. 3months after starting HT. The NADIR was short lived and each subsequent month my PSA went up, pretty much doubling each month. Tried the stopping Casodex (bicalutamide) for the withdrawal trick, but PSA just kept climbing.

I pursued two paths; clinical trials and Dr. Myers. Got both an appointment with Myers, and was accepted into a clinical trial at the National Institutes of Health (NIH). The trial involved a combination of a vaccine therapy (PROSTVAC) and Enzalutamide (Xtandi). I was fortunate to get into the arm that got both meds. Dr. Myers was enthusiastic with my participation in this trial and said Xtandi would have been his choice for my next therapy and that the Prostvac was a bonus.

By the time I started on the NIH Xtandi w/Prostvac trail in Jan 2014, my PSA had already climbed back up to 35. I was on the trial for 3 months, but my scans showed that the cancer had progressed while on the protocol, and had spread to my liver, kidneys and adrenal glands. Cancer on the lymph nodes had also grown to the point of cutting off circulation to my right leg, causing it to swell and making it difficult to lift my leg. I was also having serious BPH type issues, so prostate must have increased some as well. The Prostvac vaccine was intended as a long term immune system fight, while Xtandi was to provide an immediate attack. Unfortunately, my cancer did not respond to Xtandi and maybe I would test positive for AR-V7 as described in this article am.asco.org/androgen-receptor-splice-variant-7-linked-enzalutamide-and-abiraterone-resistance.

Regardless of my individual response on this first trial, I feel this was a great shot at the beast, and a trial that I would not hesitate recommending to others! Just my opinion, but I feel for aggressive cases, the combining of a strong drug like Xtandi with an immunotherapy, is a terrific strategy. I am hoping that the Prostvac is still in my system working along side the meds in this new trail.

Had a second consult with Myers and because of the liver and adrenal gland involvement he felt this second trial was prudent and that “I needed rapid and extensive tumor kill”.

Docetaxel (chemo) w/prednisone and XL-184 (Cabozantinib) Trial

Started trial on 5/1/14 with PSA back up to 80.05

The Prednisone (10mg) and XL-184 (40mg) pills are taken daily, and the Docetaxel (chemo) is IV dripped every 3 weeks. Two weeks after the 1st cycle of chemo I started getting some decent relief with the swelling of the right leg and much improved leg lift strength. about this same time I also started noticing significant hair loss, which continued for approx. two weeks, and then tapered off. Have lost most of my taste buds; pretty much all food tastes like cardboard. I have not experienced any nausea yet, and so far only minimal fatigue. Having some sensitivity / numbness of the fingertips, which is a common side effect of the XL-184.

PSA's 5/19=54.19, 6/9=34.58, 6/30=18.2

End of June 2014 scans

3 months into this trial the scans supported that things were going in the right direction. PSA dropped to 18.2, CT scans show tumor reduction size at pretty much all soft tissue locations. Bone scan results were mixed, with some uptick on the left hip area, but due to all other indications, not to mention how good I was feeling, they strongly suspect I'm seeing a early treatment flare effect on the scans, which may not be indicating an increase in the cancer.

Side effects over first 2 month:

Short episodes of foot burning, which is a side effect of the XL-184. Felt like I had burnt my heel and big toe in the hot sand, but I had no blistering. It was quite uncomfortable to walk for a few days. I kept applying the lotions (ammonium lactate and Hydrphor) that they prescribed, and it seemed to do the trick for now.

Have had a few ten minute long episodes of severe hand and feet cramps, Hands would cramp up into a fist position and was quite painful; impossible to open them. Not a common side effect of either med, but the clinic has observed this in other patients on the trial. Nothing in the blood work to indicate a reason, only suggested good hydration.

Hair stopped falling out, but is quite thin,and I can see my scalp (this is from chemo). Color of what hair is left, has turned white (I was salt and pepper, heavy on the salt) and this color symptom I believe is from the xl184.

Fatigue is starting to kick up a notch, where sometimes a extended stair climb can be exhausting.

July 2014

Got my 5th chemo cycle, PSA has now dropped to 12.4 (from 18.2), so still moving in the right direction, and all other blood tests look normal. Tried chomping on ice during the chemo infusion, to see if it helps with the taste buds, but the jury is still out on that. During the past few weeks noticed having very frequent heart burn and a dry cough. The docs said that both are likely a side effect from the prednisone (steroids), so they prescribe some Zantac to add to the mix of drugs.

Getting a little tricky taking all these meds, as the XL-184 has to be taken on an empty stomach, nothing to eat 2hrs before or one hour after and now since the Zantac can interfere with XL-184, have to take that no less than 4 hours after the XL-184 and at least 14hrs before. It's not so bad during the work week, with regularly scheduled meals, however weekend food consumption times can tend to be more unpredictable for us.

The weekend following the 5th chemo cycle was the worst fatigue I had experienced since the start of the trial. Got chemo on a Tues., mowed my lawn on Thurs. with no problem, but Fri thru Sun I struggled trying to do anything physical, even short stairs. I've had a week or two bout of the foot burning symptoms, pain in the heals and under the toes. It was getting difficult to walk on them, so I was prescribed new creams to apply (Urea & Clobetasol Propionate) and they seem to be doing the trick. The Zantac also appears to have done a good job on the heartburn, but still have the annoying dry cough.

Anxious to see the next scans, which are scheduled for the 2nd week of Sept., more to come....

Adjust,

Thanks for the update.  Sounds like things are heading in the right direction.  Keep us posted...

Jerry

adjust,

Thanks for posting the details. As you know, I think nothing beats the combo you are on, and as you said, the Prostvac can only help. I've heard about the scan flare you mentioned, perhaps due to the radical change in the bone environment. It's amazing how fast cabozantanib works. I'm sorry to hear about the SEs, but it sounds like you are maintaining a fairly good quality of life all the same.

I am sometimes hesitant to mention clinical trials when I know of some good one that is distant from where someone lives. There are so many great trials at NIH. If you don't mind saying, do you live near Bethesda, and if not, how did you find traveling there for the scans and assessments? Do you have a local oncologist, in addition to Snuffy Myers and the docs at NIH? Is communication at all an issue among the members of your team?

- Allen

Thanks Don,

I hope the progress continues and that future treatments can have a positive effect.

Jack

Adjust:

Keep posting, and hang in there. Your info is valuable for a lot of us who have to make decisions.

Houseboy

Houseboy, thanks for the encouragement.

Paul, We're looking forward to seeing you and Poly again a GFMPH Rochester! You're right, some New Orleans food might just kick the buds back into shape...

Update 8/19/14
Tests, appointment and 6th chemo cycle. They were concerned about the feet burning and discussed reducing the XL-184 to 20mg (from 40mg), but once they do that, the trial will not allow a patient to go back to 40mg if things do clear up. I told them I would prefer to stay at 40mg., and if they get worse, we can discuss a reduction (so far quite tolerable). Not everybody experiences this SE, and for the nurse that I see at NIH, I am the only she has who is having this issue.

A lot of stats are monitored, but the following are of some interest... Yesterdays PSA test came back at 8.67, down from 12.14! The Alkaline Phosphatase and bone specific Alkaline Phosphatase have been dropping nicely, which some studies have shown a correlation of higher numbers to bone cancer activity. For the 1st (3) chemo cycles they checked blood 2 weeks post-chemo. Notice the WBC dropped, but then recovered prior to next chemo cycle; they wanted to make sure that pattern existed before going to 3 week tests. The Absolute Neutrophil is also important because it indicates your susceptibility to infections; they do not like to see this number much below 1K/uL. This value also recovered by the next chemo cycle. Hope the columns come out, tricky getting them to align...

-------------------Chemo--|--#1----|--####-|---#2--|--###--|--#3---|--###--|--#4----|--#5----|---#6
---------------------Date--|---4/29--|--05/13-|-05/20-|-06/04-|-06/09-|--06/24-|-06/30--|-07/22-|--08/19
Unit----Ref.Range--Test--|--Value--|--Value-|--Value-|-Value-|-Value--|-Value--|--Value--|-Value--|--Value
ng/mL--0>3.99---PSA----|--80.05--|--###--|-54.19-|-###--|-34.58-|-22.15--|-18.2----|-12.14--|--8.67
mcg/L--0>20--Alk Bone--|---46----|---###-|--35----|-###--|--23----|--###--|-###----|-15-----|-####
U/L---40>130 -Alkaline--|--178----|--158----|-178---|--131--|--131---|-125----|--103----|-103----|--88
K/uL-4.23>9.07---WBC--|---4.29--|---2.97--|-6.91---|-2.35--|-4.86---|--2.1----|-6.05----|-6.9----|-5.17
M/uL-4.63>6.08---RBC--|---4.08--|--4.26---|-4.45---|-4.23--|-4.41---|--4.21---|-4.11----|-4------|-3.67
K/uL-1.78>5.38 --Neut* |--2.74---|---1.08-|--4.97---|-0.94--|-2.9----|--0.72---|-3.53----|-6.16---|-2.81
*Neutrophil Absolute

Next update after Sept 9th scans....

Post Edited (adjust) : 8/23/2014 11:15:14 AM (GMT-6)

Thanks Allen, I have Internet Explorer and am interested in making the table look good. It looked good in the "preview" panel, but I kind of thought that was not how it would come out...

I had no issues with diarrhea up until the last 3 weeks. Have had 3 bouts of it recently, but it was not all that serious, and Imodium did take care of it. Have had nothing as serious as your dad is having. Hope the Imodium does the trick.

Update 9/9 – 9/23/14
Some good news... The recent news concerning the XL-184 Phase III trial results will not have any impact on my continuation on this combo trial.

9/9 completed 7th chemo cycle. PSA is down to 6.6 from 8.67, CT Scans showed some more reduction in lymph nodes, and bones scans were stable, no new lesions. The trial doc was very please with my test results and sincerely believes the combination of these two drugs are providing me with better results than either drug may have individually.

Fatigue following the last two chemo cycles were considerably less than the 5th cycle. Feet burning is still a problem that comes and goes and have also had some minor burns on my hands and elbows this past month. These burns can be very uncomfortable at times, and seem to be worst the week immediately following a chemo cycle.

I do have one SE that I never recognized until I started viewing photos of my sons wedding... not only is my hair very thin and white, but my skin color is also quite washed out. The docs at NIH confirmed that this skin pigment change was being caused by the trial drugs.

9/19 - Spent this past weekend in the hospital due to a fever. My absolute neutrophil was down to 100/µL, where the risk of serious infection increases as the absolute neutrophil count falls to the severely neutropenic range < 500/µL (NIH reference range is 1780-5380) It's common for this number to be its lowest 10-14 days post chemo, however not that low. The lowest number I had seen at the start of the trial, at 14 days, was 720/µL. When released from the hospital this past Saturday it was up to 500/µL and today it came back at 5400/uL. Must be the booster shot I got before leaving the hospital really did the trick!

Bottom line is that the trial results are still favorable and I will continue on the trial for at least another 9 weeks (until the next scans), getting labs and chemo every 3 weeks.

Thanks for posting all this....very interesting and here's wishing you continued good results.

Great news adjust, thanks for sharing!

Hi adjust,
Glad to hear everything is well. Thanks for sharing.
Dad has been on xl184 for a little over two months and he is doing much better. Dosage was adjusted on the second week due to extreme diarrhea to 40mg. He seems to be holding ok and taking zofran twice a day. Side effects are mouth sores. One of the sore was almost the size of a dime which he stopped the meds for two days in order to heal. Other notes is sodium, magnesium, and phosphorous is low since he began xl. So he is on those supplements. Surprisingly his glucose has been low 60's-70's and he stopped a few of his diabetics meds. He is feeling better and no bone pain anymore. His bone indicator has been falling in the right direction however PSA has continued to maintain in the 1,100's (before starting was 1,000's) but bone indicator started in the 800's and now in the 300's. We are all happy with this progress. He's walking now and back in August we were wheeling him around.
Keep us updated.

Don
Thanks for the updates. So good to read that you are feeling good and that the hand and foot pain has receded. You've been on a lot of chemotherapy so I'm very glad for you that you've experienced relief.
How is the leg doing from the swollen lymph nodes? Other than the pain you described in your hands and feet, Do you have other pain/numbness/tingling in your leg(s)?
Hope you get a nice decline in your next PSA. You've certainly earned it!
Take Care,
Bryan