Neratinib Clinical Trials

Mountains1day

Anyone either in or considering in on this clinical trial?  I understand this is the next cutting edge  orally administered, anti-HER medication and may cross the BBB (Blood/Brain/Barrier).  Every HER-2 positive breast cancer patient has varying probability of relapse.  What the study is asking is, "After Herceptin, if a patient were to get one more extra year of anti-HER medication, how much reduction in relapse will this extra year of therapy give?" 

jap

Hi,

I am considering this trial and would like to know more about it.   My hospital still has it hung up in the review board but supposedly it will be available in 1-2 months..   Is anyone else on the trial?  Near Boston?

On the HER@ support list one person started the trial on September 1st.

The trial was sponsored by Wyeth but then the company was to be taken over by another drug company and the trial got stuck in the legal department.  Didn't the drug companies also hold up Herceptin?

I understand from clinicaltrials.gov that it will be open Stage I-stage IIIC HER2/erbB-2 Positive patients. 

I hope to know more soon.

Remember only 50% of the participants will actual get the drug.

Jo Anne

orange1

I can't imagine why Genentech (the manufacturer of Herceptin) would intentionally hold up the development of Herceptin.  They can't make any money on it until it is approved and available on the market.  Jap - I'm curious if you have any specific information about this.  Thanks.

jap

I haven't read the book or seen the film but it was my impression that the doctor who discovered H. had trouble with the drug industry.

In terms of the Neratinib trial, at least two places in Mass. will participate but at the moment are held up by the human subjects boards which only meet once a month.  Grr...

Jo Anne

orange1

Thanks Jap, I'm going to look into the trial

jap

I talked to a nurse at one of the hospitals which will have the trial.  I THINK this information is correct:  It is a triple blind study, one pill a day, your heart will be monitored with ECHO tests every three months (like H.), it is opened to stage I-IIIC HER2 positive who have completed H. in the last two years, 132 sites in U.S., patients followed for 5 years, etc.... You may also need to be erbB-2 positive.

Anyone else learn anything?

Jo Anne

waterlady

I have just finished reading the her2 book called "Her2" by Robert Bazell, which explains the making of Herceptin, and I found it to be very interesting reading.   Also there is a film called living proof about the herceptin story.

Mountains1day

Hi all,

I just came back from a lecture at my Onc's office, who is one chosen by Wyeth Pharmaceuticals to conduct this study in my area.  I am a potential recruit because I am early stage HER-2 positive, having Herceptin within 2 years and NED.  This is a globally randomized Double-blind placebo-controlled, and as someone here mentioned, means only half will get the drug Neratinib.  Also, it means that the study doctor won't know who has the drug or not.

The main purposes of this study are:

1.  To find out if Neratinib helps to prevent cancer from returning, or if it may help to delay the time until the cancer returns.

2.  To find out how Neratinib affects overall survival.

3.  To learn about how Neratinib affects the occurrence of brain metastases.

4.  To learn about the safety of Neratinib.

Approximately 3850 subjects is expected to take part in this study. It is expected that you will be in this study for 5 years (one month for screening, one year receiving the drug and 4 years follow-up)  Follow up tests every 3 months include ECHO or MUGA of the heart.

Herceptin and Neratinib are alike only in the aspect of each being able to target HER-2 (erbB-2).  And may pose the same side effects such as ventricular dysfunction and congestive heart failure.  The same risk as was in Herceptin that turned out to be a very small risk. My Onc said that's because our hearts naturally contain HER-2 protein and these drugs target HER-2 and affect.

Based on safety information from the subjects who have received Neratinib in research studies to date. the following side effects have been identified:

1.  Diarrhea - most can be controlled by anti-meds.

2.  Dehydration

3.  Anorexia - lack of appetite - weight loss  (I might like this one!)

4.  Nausea/Vomiting

5.  Rash

6. Abdominal pain

7. Elevated liver function tests that may indicate liver damage.

As for me, I could have signed the consent yesterday to start immediately in this study, but, I'm carefully weighing it all out as I have done with every drug thus far.  I like the idea of helping others behind me, however, I don't know the extent of my value if I already have a better than 90% overall survival given to me after I completed rads/chemo/herceptin, currently Femera and possibly Zometa in the future.  How much more can this new drug add and at what costs?  Hummmm............to be continued.

orange1

Mountains 1 Day - Thanks for posting this extensive information.

orange1

Hi Mountains,

I am in much the same position as you and contemplating joining the trial.  Did the investigators (Dr. responsible for the trial) tell you what the range of doses in the trial will be?  Thanks

Mountains1day

Hi orange1,

The dosage of Neratinib in this study is 240 milligrams daily in 6 pills.  Each pill is 40 milligrams.  They anticipate a single dose of 240 milligrams soon.  I am "on the fence" about joining this study as well.  As you, being a very early stage, I wonder how much benefit I would receive at what cost and how much I could add to the study if my prognosis is already better than 90% survival.  Also, I already attacked my cancer aggressively and may just want to trust that science as is, however, that Her-2 +++ part keeps gnawing at me.

Diagnosed 1-28-08, IDC .7mm, grade 2, Stage 1, 0/3 nodes, er/pr +, Her 2 +++ (6.5)

k4katz

Hi, I am considering looking into this study as well.  I think I may qualify, but I am not sure since my last herceptin was in December 2007, and I am currently taking tamoxifen.  I guess the big draw for me is the monitoring...whether or not I get the drug, I imagine they will do periodic exams and scans over the course of the study (which I believe is 5 years).  My BS has already dropped me to only once a year mammos and exams, and my onc is probably going to drop me annual appointments as well, and that makes me a little nervous.  I would welcome more vigilance to catch any recurrence or mets early if they happen!  Plus it would be nice to be able to support the ongoing research. 

I wrote to Wyeth and they gave me the phone number of the study location near me.  I haven't called yet...at this point I guess I will call my onc first and discuss.  He has been out of town so I have been chewing on this in my head for a few days!

*Hugs*

Kristin

Mountains1day

Hi K4katz,

Based on what I learned about meeting the Herceptin requirement, is that one must be within 2 years from last treatment.  So, you would qualify being that this December, 2009, would represent the 2 year mark.  You have 3 months to do the necessary research, talk w/your onc and make up your mind.  One factor that my cynical side is wagering, is the fact that my onc will be getting paid for each patient she brings into the study, (which is normal to be paid) however, I'm curious how she will individualize my cancer stage/conditions in terms of adding value to this study.  So far, I have just been to an informative meeting for all possible subjects and just have general info. however, I will be meeting her next week one on one to discuss more.

As for the monitoring during the 5 years, if I had insurance issues, that would weigh in a big positive as they follow you close and insurance would have to pay some things and Wyeth other things.  The downside to that is if you already have a better than 90% survival, and being exposed to a lot more radiation,complications, toxicity from too much testing........just something more to chew on.

Lori

Brenda_R

When you participate in a trial like this, who pays for everything?

k4katz

Lori, that is definitely a good point and I will add that to my list of cons!

My onc is back today and I may call him to see what he thinks.  I didn't realize that oncs get paid for bringing patients to the study!  I imagine that gives them some incentive to go into their records and identify potential participants, but also seems to me that it could work against what is in our best interests.  However, I guess it just means that we have to get all the information we can, consider all sides of the situation carefully and make the best decision for ourselves!

SSAZ

These are all good questions and I am also looking into the trial. I would not be concerned that the doctor receives some payment for enrolling you. This payment is to cover their costs (and yes, make some profit) from the additional time they will spend with you. In general, if the compensation was high enough to make it really worthwhile it would be easier to find trials to enroll in since all of the docs would be crawling over each other to participate. It would also be easier to find patients since more patients would be encouraged to participate in clinical trials which may actually help them more than current therapies and it would be easier to find trials close to home (this would be a positive). In my experience, you usually find the better physicians are involved in the trials since their work is closely watched on a regular basis and they are required to follow strict guidelines (this is good for the patient). They are also more likely to occur at major medical centers where the physician thought leaders work. When choosing between trials, however, you should keep in mind which trials your group is offering and compare it to other groups. If choosing between one or another trial, the ones offered to you may sway in favor of which trials your physician is participating in.

Mountains1day

K4katz, I understand that only the oncs who are "sponsored" by Wyeth Pharmaceuticals and agree to recruit and investigate participants get compensation.  I'm not sure if that opportunity includes all oncs, although, my onc is affiliated w/a Cancer Research Institute.  It would be helpful in sorting out some of the pros and cons associated with oncs that would be compensated and ones that wouldn't.  At the end of the day, of course, it's about the patient's individual risks verses benefit, and just as important, about helping to build valuable research as our sisters did before us! 

KristyAnn

My onc is very excited about this trial and I signed the consent forms today to participate- I dont know whether I am accepted yet and have to have a baseline MUGA.

Kristy

SSAZ

Did your onc state why this trial is exciting vs other trials that you would be eligible for? Just curious what other oncs are saying about it. Thanks.

jap

Hi,

I just finished talking to the research nurse at the hospital where I am treated about the trial.   She told me there no one gets paid extra at this hospital and the insurance covers testing and treatment.

Other information -- it will start in two to three weeks at my hospital -- once past the human subjects committee, tests required chest x-ray, physical exam, blood tests, ECHO, EKG, perhaps CAT scan if not a recent one.   Patients see oncologist every three months (now I see her only every six months) and blood tests, Muga are repeated.  You take the medication for one year but are followed for a much longer time.  Hope to have some results in 4 to 5 years.  If results positive those on the suger pill will then get the drug.  Only 50% of patients get the real thing. 

Anyone heard anything else? 

Jo Anne

SSAZ

This sounds like what I have heard. I did come across a similar trial that was done for Tykerb when it was first released. In 2006 they started a trial where 50% of patients got Tykerb and 50% got placebo after completing Herceptin. The study is closed and hopefully they will be releasing some results. Does anyone know when this would be? This would be a good chance to see what the Neratinib results may look like (although they work differently, I think they both cross the blood-brain barrier where Herceptin does not).

KristyAnn

I had my EKG, chest xray and MUGA today to get in to the study. Everything was normal and MUGA was good!

Kristy

fightinhrd123

I have my 3 more herceptins, and have prequalified for the study, so will begin all the tests in November.  I am excited to do a trial, I figure if it doesnt help me it may help someone.  Maybe we can start a thread for those doing this to help each other through

Laura

k4katz

Hello, I finally got tired of waiting for my onc to call me back and called the clinical trial location in my area myself.  The lady was really nice and, based on the information I gave her over the phone, thinks that I will likely qualify.  She is going to send me some information in the mail.  If I decide to do it, I will need to act quickly since my last herceptin was in December 2007.  She said I will need an echo, a chest x-ray and bloodwork.  If all that comes back OK, I will be in!  But I will have to do all that fast because, in another couple of months, I will be too far out to participate!.

Laura, I think it is a great idea to have a thread for the participants of this trial to share experiences.  Should we use this thread or start another one?  Who do we have so far who has definitely decided to participate?

*Hugs*

Kristin

KristyAnn

I am registered and start the trial tomorrow.

Kristy 

Mountains1day

Hi all,

I think it's a great idea to have a thread just for the participants for the Neratinib Trial.  I started this thread to increase awareness about this exciting new drug and to help provide information to those who may qualify.  Since the recruitment is ongoing and the need for information ongoing, this thread hopefully will serve us well.  Right now, I don't know of many who have actually started the trial yet.  After much consideration, I have decided not to participate, well, at least not yet.  I am just so over everything and want to move on.  Also, I have up until June 2010 to change my mind, so why not take a break.  I will definitely be following this trial and cheering for all of you pioneers on the front lines! Thank you and God Bless you!

Lori

KristyAnn

I just took my first dose- my oncologist is beside herself with excitement about this study!

Kristy 

orange1

Wow KristyAnn.  Congratulations.  Please keep us posted on how you're doing.

jap

Orange and others,

What od you know about this study in terms of effectiveness with stage 4 women (whom they try it out on first) and long-term side effects?

Thanks,

Jo Anne

orange1

This is a press release from Wyeth:

Wyeth Announces Positive Data from Phase 2 Study of Neratinib in Advanced HER-2-Positive Breast Cancer

- Global Phase 3 Program Expected to Begin in December -

     Collegeville, Pa., December 12, 2008 - Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), today announced data from an open-label phase 2 clinical trial of neratinib (HKI-272) in women with advanced HER-2-positive breast cancer.  These data suggest that neratinib has antitumor activity in patients with advanced breast cancer positive for the ErbB-2 receptor (also known as HER-2 or Neu).  These data were presented today during an oral session at the CTRC-AACR San Antonio Breast Cancer Symposium. 

     Neratinib is an investigational orally-administered potent and irreversible dual inhibitor of the HER-2 and EGFR kinases.  Wyeth expects to initiate the first study in a global phase 3 program for neratinib in advanced HER-2-positive breast cancer later this month. 

     "Neratinib demonstrated activity against trastuzumab-resistant and trastuzumab-naive HER-2-positive breast cancer," said Harold Burstein, M.D., Ph.D., a study lead investigator at Dana-Farber Cancer Institute in Boston.  "These results warrant ongoing study to see whether neratinib will fit into our armamentarium of anti-HER2 drugs."

     The phase 2 study evaluated the safety and efficacy of a daily 240 mg oral dose of neratinib in 136 women diagnosed with ErbB-2-positive locally advanced or metastatic breast cancer (stage IIIB, IIIC or IV).  The primary end point of the open-label, two-arm study was the 16-week progression-free survival (PFS) rate.  Secondary end points included safety, objective response rate (complete and partial responses) and clinical benefit rate (objective response plus stable disease).

     Patients were assigned to one of two study arms based on prior treatment with trastuzumab (Herceptin®, Genentech), the standard of care for the treatment of advanced ErbB-2-positive breast cancer.  Women enrolled in arm A (n=66) had either previously received at least six weeks of standard trastuzumab treatment or had experienced disease progression during or following trastuzumab-containing adjuvant therapy.  Women in arm B (n=70) received no prior treatment with any ErbB-2-targeted therapy, including trastuzumab.

     The efficacy analysis included 127 evaluable patients, 61 in arm A and 66 in arm B.  In patients who were previously treated with trastuzumab (arm A), the 16-week PFS rate was 60 percent, and the median PFS was 23 weeks, as evaluated by independent assessment.  The objective response rate was 26 percent, and the clinical benefit rate was 36 percent.  In patients who had not received trastuzumab treatment (arm , the 16-week PFS rate was 77 percent, and the median PFS was 40 weeks by independent assessment.  The objective response rate was 56 percent, and the clinical benefit rate was 68 percent.

     Adverse events of any grade occurring in more than 15 percent of study patients included diarrhea, nausea, vomiting, fatigue, anorexia, abdominal pain, headache and rash.  Diarrhea was the most common toxicity and was observed in 93 percent of patients.  Diarrhea was also the most significant grade 3 or 4 adverse event, occurring in 21 percent of patients.  Diarrhea was reversible and generally manageable by medication, treatment interruption or dose reduction.  One patient discontinued treatment due to diarrhea.

-----------------------------------------------------------------------------------------------------------------------------

My familiarity with stage 4 cancer is very limited.  With this caveat, based on the study discussed above, it seems that neratinib is pretty effective in Her2+ metastatic BC.

KristyAnn

My onc says the results with the Stage 4 women has been great and that is one reason she is excited- she really thinks this is the future for Her2+ and that many reoccurrences of Her2+ is because they are also positive for other HER receptors and that those are likely helped by neratinib.

Day 2 and all is well!

Kristy