A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

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DK37
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A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby DK37 » Sun Nov 20, 2016 11:36 am

Today’s Blog Post is a science one – but one I recommend all MSS-CRC patients read and consider discussing with their MD/medical team for medical advice: “A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc”

Some excerpts:
This study was very small, only 14 (!) MSS-CRC patients – and small studies sometimes do not confirm in later larger clinical trials. But signs of clinical efficacy were seen in a significant proportion of the patients including objective responses. It is also intriguing that the study showed that Maraviroc could be given both as a monotherapy as well combined with multiple types of standard of care chemotherapy for CRC – in both cases showing objective responses.

The confirmatory Phase 2 trial will be starting soon in Germany (January, 2017). The current Phase 1 trial data may only be preliminary but unfortunately the prognosis of many Stage IV MSS-CRC patients may not allow a lifespan long enough to wait for the German Phase 2 trial results to be known.

Looking at the commercial availability of Maraviroc and its preliminary clinical profile in MSS-CRC patients, it is likely that many stage IV CRC patients will be seeking the medical advice of their oncologists on its potential off-label use, especially as they begin to run out of standard of care treatment options. In my own case, my standard of care options are dwindling and my life is on the line. In that situation, it is an easy decision in my mind to ask for medical advice from my oncologist. The outcome of these medical advice discussions will be very patient specific – but I for one, know I will be having that discussion!

Recycling is good for society, good for the planet, and in this case it may be good for MSS-CRC patients!

https://adventuresinlivingterminallyopt ... maraviroc/
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
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Maddielolo
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby Maddielolo » Sun Nov 20, 2016 4:58 pm

Very interesting. and given toxicity, clinical response, and approved med, this may be better option than trials as first option following conventional chemo. Any duration reported study?

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DK37
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby DK37 » Sun Nov 20, 2016 5:23 pm

Maddielolo wrote:Very interesting. and given toxicity, clinical response, and approved med, this may be better option than trials as first option following conventional chemo. Any duration reported study?


Edit:
I missed the data the first read through.
Keep in mind this is in VERY small patient numbers, here is the survival data - all patients having exhausted all standard of care before trial:

7.32-month overall survival (95% confidence
interval, from 6.91 months to infinity).
-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

dudette
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby dudette » Sun Nov 20, 2016 5:54 pm

WHOA! Thanks for highlighting this study.

I have an appointment lined up with NCT in Heidelberg the week after next. Initially it was only meant as a general discussion whether they will take me in as their patient (I really need an oncologist or even better an oncological team that has a treatment strategy that goes beyond my current chemotherapy) but it came about that I will also be screened for two trials.

I'll be on the phone tomorrow to ask about the Phase 2 trial and check when they start screening patients. I am so excited that you brought this up. Thanks :!:
Temi
Dx 03/2015 @ age 41 - CC stage IV - pT3 N2b (14/29) cM1 (hep) L1 V1 Pn1 R1
Wild K-RAS, N-RAS, BRAF / MSS
unresectable mets liver 60% + lungs
Surgery
04/15 - sigmoid resect.
07/16 - hysterectomy (ovaries)
Chemo
05-06/15 - 4 x Folfirinox
12/15 - 02/16 4 x Xeliri + Avastin
03-05/16 9 x Xeloda
09-12/16 Folfiri + Cetuximab
01/2017 - metronomic chemo + methadone
July 20, 2107 - Temi has passed away.

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DK37
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby DK37 » Mon Nov 21, 2016 5:57 am

dudette wrote:WHOA! Thanks for highlighting this study.

I have an appointment lined up with NCT in Heidelberg the week after next. Initially it was only meant as a general discussion whether they will take me in as their patient (I really need an oncologist or even better an oncological team that has a treatment strategy that goes beyond my current chemotherapy) but it came about that I will also be screened for two trials.

I'll be on the phone tomorrow to ask about the Phase 2 trial and check when they start screening patients. I am so excited that you brought this up. Thanks :!:


Great - could you please post in this thread what you hear back from the trial? (I might not see it if it is in a separate post & also that will keep news about this trial in a single thread for others to follow). Another fellow patient who has spoke to them I think last week said they told her they expected the trial to start in January.

Best of luck,

-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

dudette
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby dudette » Thu Nov 24, 2016 7:27 am

Just to say that I'm on the case.

Haven't heard back yet. Called, sent email. Will keep nagging them. And if need the principal investigator will receive a surprise visit from me in his office next Tuesday 8)
Temi
Dx 03/2015 @ age 41 - CC stage IV - pT3 N2b (14/29) cM1 (hep) L1 V1 Pn1 R1
Wild K-RAS, N-RAS, BRAF / MSS
unresectable mets liver 60% + lungs
Surgery
04/15 - sigmoid resect.
07/16 - hysterectomy (ovaries)
Chemo
05-06/15 - 4 x Folfirinox
12/15 - 02/16 4 x Xeliri + Avastin
03-05/16 9 x Xeloda
09-12/16 Folfiri + Cetuximab
01/2017 - metronomic chemo + methadone
July 20, 2107 - Temi has passed away.

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Maia
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby Maia » Thu Nov 24, 2016 7:35 am

dudette wrote:Will keep nagging them. And if need the principal investigator will receive a surprise visit from me in his office next Tuesday 8)


Hehehe. ˄˄˄˄˄ That's the attitude! : ))

dudette
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby dudette » Thu Nov 24, 2016 12:40 pm

Update:

received a brief email from principal investigator, Dr. Halama.

They are planning to roll out a few studies with Maraviroc - he didn't elaborate whether and what type of combination trials they'll be running. Recruitment is supposed to start in February 2017.

He suggested that in the meantime I should still consider participating in other studies since recruitment might be pushed back.

Patience seems to be the name of the game. But at least something is cooking.
Temi
Dx 03/2015 @ age 41 - CC stage IV - pT3 N2b (14/29) cM1 (hep) L1 V1 Pn1 R1
Wild K-RAS, N-RAS, BRAF / MSS
unresectable mets liver 60% + lungs
Surgery
04/15 - sigmoid resect.
07/16 - hysterectomy (ovaries)
Chemo
05-06/15 - 4 x Folfirinox
12/15 - 02/16 4 x Xeliri + Avastin
03-05/16 9 x Xeloda
09-12/16 Folfiri + Cetuximab
01/2017 - metronomic chemo + methadone
July 20, 2107 - Temi has passed away.

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H is for Hawk
Posts: 103
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Location: eastern Pennsylvania

Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby H is for Hawk » Tue Nov 29, 2016 10:04 pm

I tried to get my integrative doctor to prescribe off-label Maraviroc to me, but he stongly advised against it. Normally he has been supportive for off-label use of other drugs, such as metformin. He said the FDA requires the manufacturer to label the boxes with the ominous black box warning, in this case it is:

"Black Box Warning:
HEPATOTOXICITY has been reported with Maraviroc use. Evidence of a systemic allergic reaction (e.g. skin rash or elevated IgE) may occur prior to the development of liver toxicity. Patients with signs of hepatitis or allergic reaction should be evaluated immediately."

One has to weigh the risk of liver damage with the possible benefit of tumor shrinkage. There is conflicting advice. The Maraviroc clinical trial in Heidelberg, Germany (NCT01736813) write-up on clinical trials.gov is more positive, where the site investigator states Maraviroc is "a drug has little side-effects and toxicities even on long term treatment".
H is for Hawk (57)
10/14 L. hemi-colectomy 3 x 4 x 1 cm tumor, 13/14 lymph nodes pos. pT4a N2B M0 stage 3 MSS
11/14 - 4/15 12x FOLFOX
5/15 PET scan: 2.5 x 1.5 cm l. colon lesion, peri surface lesion SUV 2.4, adenocar., KRAS wd, BRAF V600E mut
6/15 HIPEC
9/15 Pleural lining & liver mets, CA 19-9: 6000
10/15 Vectibix Tafinlar Mekinist
11/15 1500
1/16 200
2/16 100, add Lentinan
3/16 122
6/16 4500
7/16 20,000, CT scan - three new liver mets
8/16 6700, FOLFIRI
9/16 4900, CT scan - two new liver mets
10/16 2255 vinorelbine

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DK37
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby DK37 » Sat Dec 03, 2016 6:28 am

H is for Hawk wrote:I tried to get my integrative doctor to prescribe off-label Maraviroc to me, but he stongly advised against it. Normally he has been supportive for off-label use of other drugs, such as metformin. He said the FDA requires the manufacturer to label the boxes with the ominous black box warning, in this case it is:

"Black Box Warning:
HEPATOTOXICITY has been reported with Maraviroc use. Evidence of a systemic allergic reaction (e.g. skin rash or elevated IgE) may occur prior to the development of liver toxicity. Patients with signs of hepatitis or allergic reaction should be evaluated immediately."

One has to weigh the risk of liver damage with the possible benefit of tumor shrinkage. There is conflicting advice. The Maraviroc clinical trial in Heidelberg, Germany (NCT01736813) write-up on clinical trials.gov is more positive, where the site investigator states Maraviroc is "a drug has little side-effects and toxicities even on long term treatment".


During the required MD discussions for prescription(I intended for patients to have those discussions with their medical ONCOLOGIST not with a naturopath - that is why I very specifically wrote: "Looking at the commercial availability of Maraviroc and its preliminary clinical profile in MSS-CRC patients, it is likely that many stage IV CRC patients will be seeking the medical advice of their oncologists on its potential off-label use, especially as they begin to run out of standard of care treatment options. In my own case, my standard of care options are dwindling and my life is on the line. In that situation, it is an easy decision in my mind to ask for medical advice from my oncologist. The outcome of these medical advice discussions will be very patient specific – but I for one, know I will be having that discussion!"), I think it has to weighed against the likely patient population, a Stage IV CRC patient who has exhausted all standard of care options and quite frankly is facing death. Liver panel monitoring will be required. It should be treated as an oncology drug not as a less strong off-label medicine like metformin. That being said, the less strong off-label drugs like metformin have not generated the strong objective responses since in the preliminary small maraviroc trial - so they are really apples and oranges (in terms of both potential toxicity and potential efficacy) and should be treated as such...
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

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CRguy
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Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby CRguy » Sat Dec 03, 2016 10:28 pm

DK37 wrote: - so they are really apples and oranges (in terms of both potential toxicity and potential efficacy) and should be treated as such...

AND, my addendum here, whose emphasis is underlined and hopefully UNDERLINES DK37's post
"... in the context of an informed consent, doctor/patient relationship with an accredited Oncological professional, who KNOWS the relevant details of their own patient's exact situation, in the context of existing medico-legal efficacy and reality. "

AND not just .... well folks YOU figure out the rest
BUTT I am / have also been an "alt" / integrative practitioner and when I was Dx
I stuck with existing medical practices ..... WHY ?
do you feel me biting my tongue folks ?
I am.

DK37 .... Harmony bro'
ALWAYS on the Journey with you
YOU ROCK buddy

CR
Caregiver x 3
Stage IV A rectal cancer/lung met
11 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

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DK37
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Location: San Diego

Re: A Potential MSS-CRC Immunotherapy From an AIDS Drug Start: The CCR5 Receptor Antagonist Maraviroc

Postby DK37 » Mon Dec 05, 2016 10:16 pm

CRguy wrote:
DK37 wrote: - so they are really apples and oranges (in terms of both potential toxicity and potential efficacy) and should be treated as such...

AND, my addendum here, whose emphasis is underlined and hopefully UNDERLINES DK37's post
"... in the context of an informed consent, doctor/patient relationship with an accredited Oncological professional, who KNOWS the relevant details of their own patient's exact situation, in the context of existing medico-legal efficacy and reality. "

AND not just .... well folks YOU figure out the rest
BUTT I am / have also been an "alt" / integrative practitioner and when I was Dx
I stuck with existing medical practices ..... WHY ?
do you feel me biting my tongue folks ?
I am.

DK37 .... Harmony bro'
ALWAYS on the Journey with you
YOU ROCK buddy

CR


Cheers CR! :)
-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List


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