Neratinib Clinical Trials

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

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

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

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

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

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

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.

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

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

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

Kristy

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

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

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.

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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.