|
A Patients Personal Experience
with IMC-A12 and MDV3100
A press release from Medivation, Inc. on 3/18/09
"announced that it has received written permission from the U.S. Food and
Drug Administration (FDA) to begin a pivotal Phase 3 trial of MDV3100, its
novel androgen receptor antagonist, in patients with metastatic
castration-resistant prostate cancer (CRPC) who have failed docetaxel-based
chemotherapy. The placebo-controlled, double-blind, multinational trial will
enroll approximately 1,200 patients who will be randomized (2:1) to receive
either MDV3100 or placebo. The primary endpoint of the trial will be overall
survival."
"This is a significant milestone in the development
of this important novel investigational drug," said David T. Hung, M.D.,
president and chief executive officer of Medivation. "We look forward to
starting the trial and rapidly executing a comprehensive Phase 3 development
program for MDV3100. Given the encouraging results seen to date in our
ongoing Phase 1-2 trial and the limited life expectancy of men with CRPC who
have failed chemotherapy, we will work to begin the Phase 3 clinical
development of MDV3100 as quickly as possible this year."
"The FDA informed the Company that it could test a
dose of MDV3100 up to 240mg/day. There are no driving or other restrictions
placed on the activities of participants in the trial. Final trial specifics
will be announced when the first patient is enrolled."
Introduction
George Kosaly has
recently done two clinical trials in a row. He's provided some background
information on each trial as well as providing details of his actual
results. Phase II trials are often better than phase III randomized
trials as you know for sure you are getting the study drug. That doesn't
mean that your individual results will be good.
Phase II Single Arm, Open Label Study Of IMC-A12
In Asymptomatic, Chemotherapy-Naive Patients With Metastatic
Androgen-Independent Prostate Cancer
IMC-A12 is
the product of ImClone Systems Incorporated that sponsored the study.
Investigator: Celestia Higano, M. D. Seattle Cancer Care Alliance.
(Remark: This is the company that years ago had an
internal info stock scandal that landed Martha Stewart in prison. The
previous CEO is still in prison. I was assured that there was new leadership
and that they had high class researchers.)
Tumors have receptors for the insulin-like growth
factor-I. It is thought that these receptors cause tumors to grow. IMC-A12
attaches to the receptors. This may stop the tumor from growing and kill
cancer cells.
In other ongoing studies of IMC-A12 the most
significant side effect was very high levels of blood sugar.
My experience with IMC-A12 by George Kosaly.
Nov-07 PSA 3.92 Joined a Phase II Single Arm ,
Open-Label Study of IMC (Imclone)-12 (monoclonal antibody).
Nov-07 Bone scan (Restaging for new treatment.)
Findings: The increased tracer uptake involving the T7 to T9 region is again
noted and appears to have increased in intensity. The focus of increased
uptake involving the right scapular tip and right mid clavicle appear
essentially stable. The right 8th rib focus posteriorly shows mild
progression in the interval. However, the previously noted 5th metastatic
focus is stable. New foci of mild increased tracer uptake involving the left
upper ribs from 2nd to 4th ribs also show heterogeneous appearance.
Nov-28-07
PSA 11.12
Dec-03-07
First AMC-A12 infusion
Dec-17-07
Second AMC-A12 infusion , PSA 3.58 Huge drop in PSA!!!!!!!
From Dec 2007 I was given IMC-A12 infusion every
other two weeks. Had Bone Scan and CT scan every eight weeks and PSA results
at least once in every four weeks.
March-08 PSA
6.5, Bone Scan: No significant changes.
May-08 PSA
29.88, Bone Scan: No significant changes
June-08 PSA
77.95.
I have repeatedly inquired about the importance of
my increasing PSA. It was explained that the Bone Scan info is more
important and it says that the Imclone infusion temporarily stopped the
spread of my cancer.
July-08 Bone Scan: New foci are identified at ...the
left clavicle, coracoid processes bilaterally sacrum, proximal femur
bilaterally, mid and distal diaphyses on the right femur and patchy foci
...in the left distal femoral diaphysis. Compatible with interval
progression of metastatic disease.
Foci ....are identified in the ribs bilaterally,
thoracic and lumbar spines, and the left iliac bone posteriorly, compatible
with known bony metastasis. The above Bone Scan showed progressive
development of the cancer.
July-08 my
participation in the Imclone study was terminated.
July-08 PSA
147.
Side effect: After the second infusion my blood
glucose level became high. The UW Diabetic Care doctor started insulin
therapy. The hope was that when the Imclone tx would be finished my diabetes
will go away. It didn't, I am still injecting myself with insulin based on
self- measurement of my blood glucose value.
A Phase I/II Open-Label Dose Escalation Safety
And Pharmacokinetic Study Of MDV3100 In Patients With Castration-Resistant
Prostate Cancer
MDV3100 is
the product of Medivation Inc. in San Francisco that sponsors the study.
Investigator: Celestia Higano, M. D. Seattle Cancer Care Alliance
MDV3100 is a novel small molecule Androgen Receptor
(AR) antagonist selected for its ability to overcome resistance to
conventional antiandrogens (such as bicalutamide, flutamide or nilandron) when there is increased AR expression. Unlike bicalutamide, MDV3100 inhibits
AR function by blocking nuclear translocation, DNA binding, and has no
agonist activity when AR is overexpressed.
For earlier phase I/II testing with this drug, see the
paper presented by H. Scher et al at ASCO 2008. H. I. Scher, T. M. Beer, C. S.
Higano, D. C. Danila, B. Montgomery, J. Shelkey, M. Hirmand, D. Hung, C.
Sawyers,
Phase I/II study of MDV3100 in patients (pts) with progressive
castration-resistant prostate cancer (CRPC), J Clin Oncol 26: 2008 (May
20 suppl; abstract 5006). There are 39 patients enrolled. The abstract has
the following results: "In the 30 mg cohort, 3 of 3 Pts had PSA declines of
44% to 87% from baseline for 19+ weeks, and at 60 mg, 3 of 3 pts declines of
74% to 96% for 14+ weeks. None of the 6 showed evidence of clinical or
radiographic progression. Overall 13 of 14 Pts followed for 4+ weeks have
had PSA declines."
MDV3100 Ongoing Phase 1-2 Trial (18 March 2009 and
ASCO 2009)
A press release from Medivation on 18 March 2009)
gives an update on MDV3100. "MDV3100 is being evaluated in an ongoing
open-label, U.S., Phase 1-2 study of a total of 140 men with CRPC. Patients
in this trial were heavily pretreated, with all having failed standard
hormonal therapies and many having also failed docetaxel-based chemotherapy.
MDV3100 has consistently demonstrated encouraging anti-tumor activity across
dose levels and endpoints for both chemo-naive and post-chemo patients.
MDV3100 has been generally well tolerated at doses of up to and including
240 mg/day. The most frequently reported adverse event was fatigue. Patients
are continuing on study until they experience an intolerable adverse event
or until their disease progresses."
Most recently, H. I. Scher et al, presented at ASCO
2009 the updated phase I/II results with MDV3100. Sequential cohorts of
3-6 pts at 30, 60, 150, 240, 360, 480 and 600 mg/day were treated. Once the
safety of a dose was established, enrollment was expanded at doses >60
mg/day to include 12 chemotherapy-naïve (naïve) and 12 post-chemotherapy pts
per cohort .
-
No. Patients: 140 (114 pts at 30-360mg/day
followed for > 12 weeks.
-
PSA Declines (>50% decline), week 12, 57%(37/65)
if chemo-naive and 45% (22/49) if post-chemo.
-
Soft tissue radiographic control (no
progression), 74%(35/47).
-
Bone metastases 50/81 patients (62%) No bone
progression.
-
CTC counts, 101/114 patients 92% (56/61)
favorable (<5) counts pretreatment maintained favorable posttreatment
counts; 53% (21/40) converted from unfavorable to favorable posttreatment.
For post-chemo pts, favorable retention was 100% (17/17) and unfavorable
to favorable conversion at 240 and 360 mg/day was 60% (6/10).
-
At 600 mg/day, 2 of 3 pts had dose limiting
toxicity (rash; seizure). Dose reductions due to fatigue were noted at
480 and 360 mg/day.
-
The efficacy comparable to that at higher doses
and the better adverse event profile, led to the selection of 240 mg/day
as the recommended dose for a phase III trial in CRPC.
See H. I. Scher, T. M. Beer, C. S. Higano, M. Taplin,
E. Efstathiou, A. Anand, D. Hung, M. Hirmand, M. Fleisher, Antitumor
activity of MDV3100 in a phase I/II study of castration-resistant prostate
cancer (CRPC), 2009 ASCO Annual Meeting, J Clin Oncol 27:15s, 2009 (suppl;
abstract 5011).
My Experience with MDV3100 by George Kosaly.
October-06-08 Bone Scan: Interval progression of
osseous metastases. New foci of radiotracer uptake in the right temporal
bone and left mid clavicle. Increased intensity of radiotracer in the
humeral heads, coracoid process bilaterally, manubrium, femurs (with more
lesions also seen in diaphyseal femurs), acromioclavicular joints,
sternoclavicular joints bilaterally and left SI joint.
Oct-24-08 Start MDV 3100 at 480mg/day. The
drug made me tremendously sleepy all day. It also turned out that a few
people got seizures at this dose. In early December-08 the dose was changed
to 360mg/day. The decrease largely improved my sleepiness. End of December
word came from the company that even at 360mg/day the drug may cause
seizures. The new dose was determined to be 240mg/day. I am presently taking
the latter dose.
1/12/09 Bone scan on: Multiple foci of widespread
bone metastases.
Overall appearance is stable or mildly progressing.
1/12/09 CT-scan: New 1.6 cm hypodensity within the
spleen. (Until now my CT-scans were uneventful, therefore this new info is
worrisome for me. Oncologist says that this might be a radiologist error, we have to wait for the next CT-scan)
Note that for several weeks I had a strong pain in
my back which was considered cancer related. The pain left me during the
MDV3100 treatment.
Generally speaking I feel relatively well. The
oncologist finds the disappearance of the pain and my general feeling
encouraging.
New protagonist in my blood count is the platelet
number. The oncologist believes that the decrease of the platelet number is
cancer related.
Below I am giving the PSA values and platelet
numbers measured during the MDV3100 treatment.
Oct-06-08 PSA 446, Platelet count 127
Oct-22-08 PSA=491,
Platelet count 118
(Above two values refer to
dates
before MDV3100 was started)
Oct-24-08
Start MDV3100.
Nov-18-08 PSA 458, Platelets 50.
Dec-02-08 PSA 388, Platelets 37.
Dec-16-08 PSA 409, Platelets 47.
Jan-5-09 PSA 630, Platelets 47.
Jan-12-09 PSA 550, Platelets 52.
The above table says that the PSA value first
dropped, then increased and dropped again. The platelet number decreased and
seems presently inching upward. The oncologist wants to have five more weeks before
she arrives at a conclusion regarding my cancer's reaction to the drug.
1/24/2009. Some weeks ago I felt real well on the MDV drug.
Recently my feeling of malady became stronger, I nearly stopped doing my
research work.
At the same time there was a one-week break in
taking the MDV-drug and following that time my platelet count improved. From
all this Dr. Higano concluded that the MDV-therapy did not work. The decision
is to start chemotherapy next week, probably taxol+carboplatin.
Note: George Kosaly succumbed to his HRPC disease 8 June 2009.
|
