New Clinical Trial for neuroendocrine tumors sounds promising

From The Caring for Carcinoid Foundation web site

 

 

Theragnostics of Neuroendocrine Tumors with Somatostatin Antagonists

Peptide Receptor Radionuclide Therapy (PRRT) is a technique widely used in Europe for the management of patients with metastatic neuroendocrine tumors.  There are currently clinical trials in the United States for PRRT with somatostatin agonists as described below.

PRRT delivers targeted radiation therapy by exploiting the physiology of neuroendocrine tumors. Most neuroendocrine tumors, including carcinoid, have specialized cellular receptors that bind to somatostatin, a hormone that exists naturally in the human body. Scientists have developed artificial “analogs” of somatostatin to attach to these receptors.  These are called somatostatin agonists and they include agents like octreotide. Somatostatin agonists are able to target neuroendocrine tumors by binding to the somatostatin receptors present on tumor cells.

The PRRT currently in use typically combines a somatostatin agonist with a radioactive substance called a radionuclide to form highly specialized molecules called radiopeptides. These radiopeptides can bind receptors on tumor cells where they emit radiation that can either 1) be read for diagnostic imaging or 2) kill tumor cells.

Studies have suggested that PRRT with somatostatin agonists can lead to a decrease in tumor size and alleviation of symptoms in some patients.  However, not all patients respond and there can be serious side effects including kidney failure.   To date, randomized prospective clinical trials, of the nature typically required by the FDA for regulatory approval have not yet been completed.  However, there is currently a prospective randomized clinical trial of PRRT with somatostatin agonists in the United States enrolling patients at multiple centers.

The Memorial Sloan-Kettering Clinical Trial 

To improve effectiveness while reducing side effects, Dr. Weber and his collaborators have developed a technique for “next generation” PRRT.   Instead of somatostatin agonists, this next generation PRRT will employ somatostatin antagonists. Based on preclinical data, Dr. Weber believes that somatostatin receptor antagonists can be more effective and generate fewer side effects than the substances that are currently being used to treat patients.

Specifically, this trial will assess the potential viability of 68 Ga-DOTA-JR11 and 177 Lu-DOTA-JR11 as a pair of diagnostic and therapeutic radiopeptides for neuroendocrine tumor patients. Gallium 68 is a radionuclide that can be used in diagnostic PET scans. Lutetium 177 is a radionuclide often used with somatostatin analogs to form therapeutic radiopeptides. This study will assess the sensitivity of gallium 68 and the safety of lutetium 177 when combined with the somatostatin antagonist, DOTA-JR11 developed by the researchers. Eight patients with progressive, metastatic and inoperable tumors will participate in a clinical trial of peptide receptor radionuclide therapy with the somatostatin antagonist DOTA-JR11.  Thanks to funding from another large Foundation these eight patients will enroll alongside an additional 12 patients for a total of 20 patients enrolled.

This trial may provide proof of concept data to assess the potential for peptide receptor radionuclide therapy with somatostatin antagonists as a new treatment for patients in the United States. Furthermore, strong data from this trial could enhance the commercial potential of these specific compounds. This could pave the way for development of a new treatment and diagnostic imaging strategy for patients with neuroendocrine tumors in the United States.

Institution: 

Memorial Sloan - Kettering Cancer Center

Investigator: 

Wolfgang Weber, M.D. Ph.D.
Diane Reidy-Lagunes, M.D. 

Amount: 

$250,000

Duration: 

2 years

Research Objectives: 

1. Assess biodistribution and tumor uptake of 68Ga-DOTA-JR11 and compare the sensitivity of 68Ga-DOTA-JR11 PET with conventional imaging
2. Determine tumor and normal organ doses after administration of 177Lu-DOTA-JR11; and
3. Obtain preliminary data on tumor response to 177LU-DOTA-JR11.

Abstract: 

Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs has been developed in the 1990s, and is now frequently used in Europe for treatment of metastatic neuroendocrine tumors. However, not all patients respond well to PRRT; there are serious side effects, most notably chronic renal failure due to the renal excretion of the radiopeptides.  Thus, there is a clear need to develop new ligands with higher tumor uptake and a more favorable tumor-to-kidney dose ratio.

To address this need, members of our group have developed radiolabeled somatostatin receptor type 2 antagonists. These are the first radiolabeled somatostain receptor antagonists.  In this project we will study the second generation somatostatin receptor antagonists, 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11, as a pair of diagnostic/therapeutic radiopharmaceuticals (theragnostics) in patients with neuroendocrine tumors. Specifically, we will (i) assess biodistribution and tumor uptake of 68Ga-DOTA-JR11 and to compare the sensitivity of 68Ga-DOTA-JR11 PET with conventional staging procedures; (ii) determine tumor and normal organ doses after administration of 177Lu-DOTA-JR11; and (iii) obtain preliminary data on tumor response to 177Lu-DOTA-JR11.

We will conduct a clinical trial including 8 patients with well to moderately differentiated, progressive and inoperable midgut carcinoids. Patients will first undergo a PET/CT with 68Ga-DOTA-JR11. Patients with sufficient tumor uptake of 68Ga-DOTA-JR11 will be offered therapy with 177Lu-DOTA-JR11. Therapy will be preceded by a dosimetric study to determine the amount of radioactivity that can be safely administered.

May flowers and good health

Being in Hawaii for the month of April was glorious.  I really did swim and snorkel everyday. Peter came with me for the first 10 days and my girlfriend from Hood River came for a week after that. The last week I was on my own. My "other" son Leo and his wife Genevie and 2 boys live on the Big Island and I spent good family time with them. Leo came to live with Thaddeus, Jessica and I when he and Thaddeus were best friends in the 5th grade. We were blessed to have him be a part of our family for many years after. Not long after he turned 18 he moved to the Big Island and met his future wife.
When the kids were little our main vacation spot was the Big Island and we had many exciting 2 and 3 week vacations there. I always seemed to have one friend or relative that lived there and welcomed us to stay making it an affordable vacation with 3 kids. I'm glad that my introduction of Leo to the Big Island led to him relocating and starting his family there. We enjoyed going out to lunch, dinner and evening music during this trip. We reminisced also that I introduced he and Thaddeus to African Drumming around the same time we took that first trip to the Big Island. Both boys ended up having a love of African Dance and Drumming that has continued into their adulthood. When parenting teen agers it is always beneficial if you have a hobby or 2 that you do together. One that is challenging enough and that the youth involved can excel at and even pass the adult up in their skill level. I enjoyed a drumming class with Thaddeus and Leo every Thursday night for years. We had a great time together. They surpassed me and went on to incorporate music into their lives in various ways. For Jessica and I it was walking, running, going to the gym, taking abs buster classes and of course shopping. She definitely surpassed me in these areas as well. :-)

It's funny how being retired I think about the past now in a different way than I did. I'm fond of the activities I carried out and those who played staring roles in my various life trends and era's. Also how I start out on one story (Hawaii) and end up talking about something entirely different (kids raised).

I did miss my kids, grandkids, mom, family and friends being gone almost a month. I enjoyed the sunsets and the swimming with the dolphins and turtles so much that I continually thought about how nice it would be share the experience with my whole family. Maybe someday we can all go together. Upon return I started back up with the babysitting routine. I watch Jessica's daughter, Paityn (Pai Pai) on Monday and Wednesday and Thaddeus's kids, Kimani and Ayana on Tuesday's. Thursday and Friday are free days and my friend Louise still helps me on Monday and Wednesday's and took over while I was gone. Imagine arranging my own substitute.

I'm very pleased to announce that I did well on the health front during my trip. For the last 10 days I did need to give myself 3 shots a day of Octreotide in the tummy since they don't give the every 28 day, long acting shot of it on the Big Island. The sub Q shots I gave went into the area on my stomach where I have no sensitivity from the surgeries, so I didn't feel it.  I did feel a little worse with the shots than I do with the long acting version though, a little more hormonal fluctuation and intestinal upset.

My return to regular life here in Seattle was a bit bumpy too. I had a red eye flight with a lay over in LA. I did not sleep on the flight. I arrived home to wonderful 85 degree weather but couldn't sleep that night (it was hot) after getting a call that the mammogram I had before leaving did result that a biopsy was needed of the left breast and lymph node area. So arriving home Thursday morning I had the biopsy Friday morning at 7 am. I also gave blood for my every 3 month labs and got my long acting Octreotide shot that morning. The short acting and long acting merged together weirdly and it felt very different. The combination of all this and the time (3 hours difference) and weather change (it then started raining and was in the 50's) caused a day or 2 of rest to be needed. Peter, my mom and Jessica helped remind me to take care of myself. Also hanging over my head was a bone scan scheduled for the following week. The great news is that the biopsy was benign and the bone scan showed no growth of the metastasis in the hip and back.. In my last entry I mentioned that the last CT scan also showed no growth and that there was no longer any cancer in the thyroid.  From all indications I have a 4-6 month period now where all looks good and I can enjoy the summer and eating healthy and exercising. We want to continue in this direction indefinitely.

Helping me to feel good the Lake Ridge outdoor pool opened Mothers Day and I hope to start swimming laps one of these days soon. Mothers Day was really special this year since my mom is recovering well from back and neck surgery, my health is stable and we have 2 new baby girls in the family who were not here last year. It was Jessica's first Mothers Day! We all gathered at my house and shared a healthy meal. Lots of good pictures taken.

I had my first Pilates lesson the other day and think I'm ready to start back in with an abdominal core body strength work out. I know it is good that I have gained - not lost weight but the weight gain is a bit too much now. :-) I'm hoping to drop 20 pounds over the summer by reintroducing exercise into my routines. I'm walking about 2.5 miles per day now. A great mental health plus is that I've developed a friendship from the NET support group with a guy who has NET's with a very similar medical history to mine. It is good to compare notes and to laugh about the diarrhea and other uncomfortable side effects of either the cancer or the medication. Both of us know every day is a blessing.

Another blessing about being in Hawaii for a month was the amount of reading and listening to CD's I was able to do.  I love affirmations. May I be safe, may I be healthy, may I be at peace and may I live with ease - love this. I like saying these for myself, for others and for all of us. I also have a daily calendar by Louise Hay and published by Hay House. There are so many great affirmations that I'm reading them every morning over and over again. Here are some of my favorites.

I am grateful to be alive today. It is my joy and pleasure to live another wonderful day.

I let go of fear and doubt, and life becomes simple and easy for me.

Good health comes from love and appreciation.

I am able to make correct decisions. I recognize my own intuitive ability.

I trust my inner wisdom.

I easily let go of everything I know longer need. (like tumors :-)) Another similar one: Today I easily release all that my body no longer needs. (With healthy eating and living the tumors are shrinking and going away-I'm certain of it)

I give myself the green light  to go ahead, and I joyously embrace the new.

I expect good experiences to come to me. All is truly well in my world.

Today I trust that my future is in good hands.

I move beyond past limitations into the freedom of the now.

I am centered and focused, I feel more secure each day.

I use my mind and thoughts to enhance my life.

A smiling face and joyful, loving words are the best presents I can share with all those I know.

It is only a thought, and a thought can be changed.

Wherever I am, I always have an enjoyable time.

It feels good to know that I am safe and I am loved. ( I feel so good about all my relationships)

Today I take a moment to count my blessings. (and there are many)

I have a harmonious relationship with my family. (yes)

I express who I am in joyous, positive ways.

I express love and create harmony wherever I go.

As I go through my day I am aware that the Universe (God, my family) loves me.

Today I look for the good in my life and that is what I find.

I am always safe no matter what doorway I pass through.

Today I enjoy every minute of what ever I'm doing.

For every problem that I may create I am confident that I can find a solution.

Patience is being at peace with the process and pace of life.

My body is always doing its best to create perfect health.

I choose only thoughts that create a wonderful future, and I move into it now.

Positive affirmations create my future while making me feel good in the moment.


Believe it or not these are only a few of my favorites but you get the idea. My wonderful future includes family reunions, playing with grandchildren, spending time with my mom; boating, travel, home projects and movies with Peter, the annual Native canoe journey, swimming, sauna's, walking, farmers market's, organic whole foods, lemon water and lots of restful sleep.

In closing I wanted to mention once again that Peter has been a constant in this cancer journey. Most recently he went with me for the biopsy and bone scan and even came home from work quickly one day when I was babysitting and didn't feel well.  His band the Peter Jamero Project played recently and sounded great as usual. He sang a song, which was new and sounded great. His children, sisters and dad are also a joy to know.
My mom and I are enjoying each others company more than ever. Is it possible to love her even more than I always have? :-) She is supportive and understanding and such a great - great grandma! My son and daughter continue to inspire me to be a better and better person. These 3 grandchildren are the cutest, sweetest and most well behaved kids I think I've ever experienced. No really!

Life is just so good and all my May flowers are blooming!