Trial drug - Selinixor (KPT 330)

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ramg_sg
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Joined: Tue Oct 04, 2016 1:28 am

Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Wed Dec 28, 2016 4:43 am

Hello,

FOLFIRI + Zaltrap - after 3 cycles did a PET scan. It is not containing mets. Some have increased in size and new spots in lungs were found.

Onco suggested that adding Regorafenib to the above chemo regimen may not produce wanted results, other than inviting the side effects of Regorafenib.

Discussed the trial drug Selinixor (KPT 330), which is in Phase-1 drug expansion stage in SG. I read in Karyopharm website that this is in phase-2b in other countries. I am not sure whether this is used to treat CCR.

Any feedback from the forum on this drug? I did a search in the forum, but no results. Please let me know.
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

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Maia
Posts: 2443
Joined: Fri Aug 24, 2012 8:00 am

Re: Trial drug - Selinixor (KPT 330)

Postby Maia » Wed Dec 28, 2016 8:54 am

ramg_sg wrote:Any feedback from the forum on this drug? I did a search in the forum, but no results. Please let me know.


It's a quite new drug and, coming from Asia, not quite well known but it does have results for colon.
The trial you have been offered is this one:

https://clinicaltrials.gov/ct2/show/NCT02078349

which is phase I and for solid cancers, not specific for CRC. *However*, you can be encouraged because there are other trials, higher phase, with this agent, and in combinations (which means that there is information about dosage and safety) and, as I've said, specific results for colon cancer.

Selinixor (KPT 330) is oral, a small molecule inhibitor of CRM1 (chromosome region maintenance 1 protein, exportin 1 or XPO1) (https://www.cancer.gov/publications/dic ... rid=734824)

2014: "an update on 35 patients with heavily pretreated metastatic CRC (2-8 prior regimens including anti-folates, irinotecan, and oxaliplatin as well as bevacizumab, cetuximab, and/or regorafenib in many patients) whose tumors were progressing on study entry, from the ongoing Phase 1 dose escalation study in solid tumors. Patients were treated with oral Selinexor at doses ranging from 3 to 35 mg/m2. One patient had a partial response by standard RECIST (Response Evaluation Criteria In Solid Tumors) criteria and had remained on study for eight months. Eleven patients had stable disease; ten for eight weeks or longer with four of those ten patients (11%) demonstrating stable disease for over 25 weeks. Two patients were not evaluable for response, and 21 had progressive disease at first evaluation." (...) "Dr. Sorensen commented, "This cohort of heavily pretreated patients with advanced CRC has received as many as eight prior regimens, each with several anti-cancer agents. These are incredibly sick patients with tumors that are growing on study initiation so we are excited about these early data with single-agent oral Selinexor. We look forward to obtaining additional data from cohorts at higher doses and from combination studies of oral Selinexor with already available anti-cancer agents."
More: http://investors.karyopharm.com/release ... eid=820491

Safety and antitumor activity of selinexor (KPT-330), a first-in-class, oral XPO1 selective inhibitor of nuclear export: A phase I study expanded with colon cancer cohort. http://meetinglibrary.asco.org/content/122055-143 (it was for this trial: https://clinicaltrials.gov/show/NCT01607905)

2015: data about a trial with Selixinor for ovarian cancer: http://investors.karyopharm.com/release ... eid=915585

Other pertinent trials with Selixinor ongoing in other locations, for those interested:

Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor In Patients With Metastatic Colorectal Cancer (SENTINEL) (Belgium and Germany) https://clinicaltrials.gov/ct2/show/NCT02384850
Selinexor Combined With Standard Chemoradiation as Neoadjuvant Treatment in Locally Advanced Rectal Cancer
(Israel) https://clinicaltrials.gov/ct2/show/NCT02137356
Phase IB of Selinexor in Combination With Standard Chemotherapy in Patients With Advanced Malignancies
(M.D. Anderson, Texas) https://clinicaltrials.gov/ct2/show/NCT02419495

Best of luck, ramg!

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ramg_sg
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Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Thu Dec 29, 2016 2:06 am

Maia, thank you for your detailed reply. I intend to give be my consent for the trial today and go through the evaluation phase.
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

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ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Tue Jan 03, 2017 12:51 am

There is a requirement to undergo biopsy before I start with this drug. I agreed to this, which would be done with CT assistance. The comparatively easy spot to reach will be my lungs as the sports in pelvic are are difficult to reach with other arteries nearby. Interventional radiologist will perform the same and a parthologist will confirm that the sample is right before completion of the procedure.

Is requirement of biopsy a standard one for trials ?
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

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Maia
Posts: 2443
Joined: Fri Aug 24, 2012 8:00 am

Re: Trial drug - Selinixor (KPT 330)

Postby Maia » Tue Jan 03, 2017 6:14 am

ramg_sg wrote:Is requirement of biopsy a standard one for trials ?

Yes, it is. They could rely on archived biopsy, from the primary, for example, but better to know exactly what it's been treated, since sometimes, metastasis might be different (they might present a mutation now). That doesn't happen often, but with a fresh biopsy you're more over secure ground.

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ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Thu Jan 12, 2017 1:55 am

I sort of 'escaped' from the Biopsy, as my left leg had swelled and I had pain on the day before the admission day. My Onco vetoed the Biopsy and admitted me to check reasons for the swelling.
My stay at the hospital was used for other preliminary tests for Trial drug and other tests for the swelling. I also had 38.5+ fever. Fever due to infections were ruled out with blood tests, culture, chest Xray and also a CT scan. As the fever had subsided and the reason for that was could be blood clot in Iliac vein and DVT in that leg. I started the Chemo with Trial drug yesterday 11-Jan-17. I may be facing some side effects in the next few days.

The blood clot had surfaced in Sep-16 with swelling on left leg. This went away completely in 4-5 days after I started on Rivaroxaban blood thinner, but having started the blood thinner, I had to continue with it. The swelling and associated pain surfaced on 30-Dec-16 and started to increase. For the purpose of biopsy, I had stopped the thinner for couple of days.. but as Biopsy was vetoed by my Onco, they started me on sub-cutaneous insulin like injections (Lovenox - Enoxaparin sodim).

These are the developments. Will update on the side effects of Selenixor or Lovenox. Wish me luck !!
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

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Maia
Posts: 2443
Joined: Fri Aug 24, 2012 8:00 am

Re: Trial drug - Selinixor (KPT 330)

Postby Maia » Thu Jan 12, 2017 4:49 am

Sorry to hear about the clot, ramg, but glad the doctors found the cause of the pain and they are working on the fix!
And how good that didn't preclude you from this trial, biopsy or not!
Wishing you the best, keep us, fellows at the forum, posted!!

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ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Mon Feb 13, 2017 11:52 pm

I managed to withstand 1 full cycle of Selinixor (twice a week of 60 mg each time for two weeks). Then had a break for a week.
This drug made me lose my appetite, one bout of diarrhoea (controlled with Loperamide), and significant tiredness. With my DVT, it was quite bad. I had to be hospitalized to monitor the DVT and pain management and lost about 5kg.
So my onco reduced the dosage to 40mg - twice a week. I took it for a week and had severe abdominal pain (cause unknown), one bout of diarrhoea (took 3 days to control with Loperamide) and significant tiredness.
My Onco asked me to discontinue the drug in the second week.

I have the PET scan later this week and will know whether Selinixor worked. If it hadn't, what is next????
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

Achilles Torn
Posts: 83
Joined: Fri Dec 16, 2016 2:41 pm

Re: Trial drug - Selinixor (KPT 330)

Postby Achilles Torn » Tue Feb 14, 2017 1:40 am

It may have worked. Otherwise what about Immunotherapy combo trial. Off label Maraviroc with chemo. Lonsurf ?

Pardon my ignorance but what does S3C refer to in your signature?
40 yo Male. BC Canada. Sigmoid Colectomy Dec. 2016
Pathology T3N2bM1 19 of 24 Nodes Positive + tumour deposits
PET scan - Para-Aortic and Iliac Lymph node spread. Stage VI.
Moderately differentiated. MSS. KRAS/BRAF Wild.
Mutations: TP53, ERBB4, MLL3, PDCD1LG2, PRKDC, SMAD3
FOLFOX Commenced Jan 9/2017 - Avastin(Bev) added after round 1.
June 2017 Dose Reduction on Round 11 due to Neuropathy.
Good PET Scan July 2017 - on maintenance 5FU/Bev every 2 weeks until progression.

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ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Wed Feb 15, 2017 12:50 am

Achilles Torn wrote:It may have worked. Otherwise what about Immunotherapy combo trial. Off label Maraviroc with chemo. Lonsurf ?

Pardon my ignorance but what does S3C refer to in your signature?


If this is not working, then the Onco suggests MSS, immunotherapy trial (I am MSS, and this trial is meant for MSS with MEK inhibitor) ... I have to read what is MEK yet..

S3C - Stage III C (Dukes) at the time of initial diagnosis
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

User avatar
ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Fri Feb 24, 2017 1:17 am

Selinixor is NOT working for me. The PET scan revealed no containment and only showed interval growth. Also the drug made me very tired and I couldn't take it. I was feeling very sleepy during the day (unable to keep my eyes open for few mins - could doze off during a conversation). My Onco suggested that I drop this trial drug.

Options open:
Standard suite:
a) Regorafenib (aka STIVARGA)
b) TAS-102

Trial:
PDR101 + Ilaris (immunotheraphy trial in Phase 1b). Not tried for Met CRC. If I say yes, I will be first person.

The Trial Doc wasn't favouring me going for the PDR101 trial and suggested TAS-102 - as this is meant for Met CRC. I will have to wait for 3 weeks for the medicine to be imported from Japan and it costs a bomb.

I am included to go for TAS-102. Any feed back or comments?
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

Achilles Torn
Posts: 83
Joined: Fri Dec 16, 2016 2:41 pm

Re: Trial drug - Selinixor (KPT 330)

Postby Achilles Torn » Sat Feb 25, 2017 12:28 am

Hey Ram. TAS-102 I believe is Lonsurf. I don't have experience with it but there is evidence it holds some people stable. If you can't find a trial - There is an AIDS drug called Maraviroc that you may also want to consider getting. Google Tom's Terminally Optomistic blog where he describes a phase one study on it in Germany.

Cheers
AT
40 yo Male. BC Canada. Sigmoid Colectomy Dec. 2016
Pathology T3N2bM1 19 of 24 Nodes Positive + tumour deposits
PET scan - Para-Aortic and Iliac Lymph node spread. Stage VI.
Moderately differentiated. MSS. KRAS/BRAF Wild.
Mutations: TP53, ERBB4, MLL3, PDCD1LG2, PRKDC, SMAD3
FOLFOX Commenced Jan 9/2017 - Avastin(Bev) added after round 1.
June 2017 Dose Reduction on Round 11 due to Neuropathy.
Good PET Scan July 2017 - on maintenance 5FU/Bev every 2 weeks until progression.

User avatar
ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Mon Mar 06, 2017 6:23 am

AT, Yes TAS102 is known as LONSURF in US. I have started on it and hope it holds me stable as I had better results with 5FU. I have PE (Pulmonary Embolism - clot in lung) and also some mets in lung. These are worrying me more. I have to restrict my movements so that I reduce my short of breadth. Wait to gather my breathing, before I proceed. Tough....
Age 53[2016]
07/13 Tumor discovery
08/13 CC surgery, 9/12 Lymph nodes, Temp Ileostomy T3 N2b S3C KRAS+
08/13 to 01/14 - FOLFOX+Bev & Zometa, 5FU 24x7 CEA normal
02/14 RT
04/14 Ileostomy reversal
05/14 to 06/15 - 5FU 24x7
06/15 Fix Hernia Ileostomy site
06/15 to 02/16 - 5FU 24x7
02/16 PET tumor size increase - FOLFOX+Bev
05/16 RT
07/16 PET - spots in lungs, surgery option drop
Microsatellite stable
09/16 PET - FOLFOX not shrinking tumors
09/16 FOLFIRI+Bev - 3 cycles
11/16 FOLFIRI+Zaltrap - 3 cycles

User avatar
Maia
Posts: 2443
Joined: Fri Aug 24, 2012 8:00 am

Re: Trial drug - Selinixor (KPT 330)

Postby Maia » Mon Mar 06, 2017 7:01 am

ramg, hope the Lonsurf gives you good results to get you out of the present situation. It's very logic from your doctor to recommend that now. BUT the trial he's proposing you is immunotherapy (that you haven't had until now), a very good combination.
The drug is PDR001 (not PDR101). It's just the anti PD-1 from Novartis (similar to Opdivo and Keytruda). You see less data/ no data on it because that company got later in the "race", that is all. So they are making their bets on combinations. And all of the ones in this trial are very good ones:

The trial is

"A Study of PDR001 in Combination with CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
*# NCT02900664
*Arms specific for CRC (only MSS)
*Combination: PD-1 checkpoint inhibitor (PDR001) + other four agents with immunomodulatory activity (one of them)
https://clinicaltrials.gov/ct2/show/NCT02900664
*_Four_arms_for_CRC. Non randomized. According to tumour characteristics/mutations, CRC patients are assigned to one of the following combinations:
** aPD-1 +canakinumab (Ilaris ; anti IL-1β (monoclonal antibody targeted to interleukin-1 beta), FDA approved anti-Inflammatory, injection)
** aPD-1 + CJM112 (monoclonal antibody targeted to interleukin-17)
** aPD-1 +trametinib (Mekinist; MEK inhibitor, FDA approved, oral)
** aPD-1 + EGF816 (mutant-selective EGFR tyrosine kinase inhibitor; oral)
*Recruiting
* Tennessee, Texas, Belgium, Canada, Singapore, Spain

(I put in bold the trial your doc was thinking to include you in).

Other trial that you have in Singapore is other with the same drug, in other combination:

-----------

"Phase I/Ib Study of GWN323 Alone and in Combination With PDR001 in Patients With Advanced Malignancies and Lymphomas"
# NCT02740270
https://clinicaltrials.gov/ct2/show/NCT02740270
*Combination (PD-1 checkpoint inhibitor (PDR001) + anti-GITR GWN323 ) and monotherapy (anti-GITR alone)
*Advanced malignancies
* Recruiting
* Illinois (U. Chicago), Massachusetts (Dana Farber), New York (MSK), Texas (MD Anderson), Canada, Israel, Singapore, Spain

Both trials have a lot of rationale, in its mechanism of action, for CRC.

User avatar
ramg_sg
Posts: 35
Joined: Tue Oct 04, 2016 1:28 am

Re: Trial drug - Selinixor (KPT 330)

Postby ramg_sg » Wed Mar 08, 2017 2:02 am

Maia, Thanks for your detailed reply.

The Trial Onco, checked me and somehow felt that I am not 'physically' ready for PDR001+Ilaris trial. As I have PE and lung mets, I have shortage of breadth. Probably that's one of the reasons he wasn't keen to enroll me. Anyway, I am onto Lonsurf this week and let us see.


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