ILC Clinical Trials

Update | August 2015: The first ever ILC clinical trial has started!
This is a trial focused on women who were "just diagnosed" and have not had surgery yet.

Oct 2015 Press Release: "Magee-Womens Hospital of UPMC (Pittsburgh): Clinical Trial Opens to Examine Therapies on Invasive Lobular Breast Cancer"

The University of Pittsburgh,Magee-Womens Breast Cancer Program has launched a pre-surgical "window" Trial to identify Biomarkers of endocrine response in ILC. They will be treating patients during the ~3 week period between initial diagnosis and surgery, using 1 of 3 standard endocrine therapies [Tamoxifen or Arimidex or Faslodex], and then comparing Biomarkers at pre-therapy (diagnosis) against post-therapy (surgery).
The goal is to assess how ILC tumors are responding to the different endocrine therapies.
** The clinical trial is called: "A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer" and enrolling ~150 patients. Press Release is here.

In addition to the primary site of Pittsburgh, Pennsylvania, other locations where you can participate in this Trial include:

1. MD Anderson in Houston, Texas
2. Mayo Clinic in Rochester, Minnesota
3. University of Washington in Seattle, Washington
4. University of Alabama in Tuscaloosa, Alabama
5. Dana Farber in Boston, Massachusetts
6. University of North Carolina in Chapel Hill, North Carolina

* Note: As of Nov 2015, these sites have not officially opened, but will within the next 6 months.

I'm honestly unsure about how others feel, but I think this is a critically important trial.
If anyone with ILC expects progress, it's crucial that new ILC patients (who have NOT had surgery yet) know about this trial. Only new patients who are Stage 1 through Stage 3 are eligible to participate.

There's so little research being done on ILC (compared to other subtypes). I've identified small groups in Belgium, Netherlands, New Zealand and tiny pockets of the U.S. and I hope that the silos of data each group generates is shared among each other. At the current pace, it will take a decade before ILC pathway targets are clinically available, unless projects like these are executed efficiently. The sooner patients enroll, the sooner the data is generated, the sooner new therapies arrive.
Until then, little will change. ILC patients will continue to receive treatments that were not designed for them and the game of "roll the dice" continues. That's why a trial like this is important.
It's not much, but a baby step in the right direction is worth more than a mile down the wrong path. It would be a shame if this trial was cancelled due to lack of participation.

Who else shares this sense of urgency?

Were Stage IV ILC patients aware of this Lobular trial?

LGK974 for Metastatic Lobular Breast Cancer
A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Melanoma and Lobular Breast Cancer (NCT01351103) Source: www.breastcancertrials.org

Here's the trial on clinicaltrials.gov: A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands.

The drug "LGK974" is a Porcupine inhibitor developed by Novartis Oncology. Porcupine is tied to WNT signaling.
Source 1 and Source 2 [must copy & paste] http://www.novartisoncology.com/ct/pipelineDetails...
Researchers suspect that the "WNT" pathway is partially responsible for controlling ILC growth.

Here's deeper info on LGK974, the Small molecule inhibitor of Porcupine from the Novartis website.

Here's some related 2013 Novartis research: "Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974".

I'm surprised no one here brought up this clinical trial before, especially since it's been around for a number of years.
Perhaps it fell through the cracks since the clinicaltrials.gov page lacks reference to Lobular, ILC, or anything else that would allow a Stage 4 ILC patient to find it.
Interestingly, BreastCancerTrials.org listed this trial on their site as: "LGK974 for Metastatic Lobular Breast Cancer".
[must copy & paste] https://www.breastcancertrials.org/bct_nation/brow...

Trial sites include:
US, Maryland - Sidney Kimmel Cancer Center at Johns Hopkins
US, Massachusetts - Dana Farber
US, Michigan - University of Michigan
US, Texas - MD Anderson
Netherlands... Rotterdam
Spain... Madrid & Barcelona

Perhaps, this warrants a thread in the Stage 4 section, including a post to this thread "Stage IV ILC: Tests, Treatments, News--Let's pool our knowledge". Feel free to copy and paste.

2016 update: The Porcupine inhibitor, "LGK974" is now known as "WNT974".

Big news!! A clinical trial called POSEIDON focused solely on Lobular!
plus
A second clinical trial called SANDPIPER that may benefit Stage 4 Lobular.

"Ground-breaking European clinical trial testing new investigational drug for the treatment of ILC breast cancer"

05 October 2015

Cancer researchers, oncologists and international pharmaceutical company join forces to test a new investigational drug for ILC breast cancer

The progress of a large pan-European clinical trial, called "POSEIDON" into a novel targeted study drug (called Taselisib or GDC-0032) for breast cancer was announced today by the collaborative RATHER project funded by the European Commission. The POSEIDON clinical trial centres, based in the Netherlands Cancer Institute (Amsterdam), Cambridge Cancer Centre (UK), and the Vall d'Hebron Hospital (Barcelona, Spain), began to study patients treated with this investigational drug in December 2014.

The RATHER project focuses on finding new drug targets for two types of breast cancer - invasive lobular carcinoma (ILC), an aggressive cancer that does not respond well to current treatments, and triple negative which lacks the ER, PR and HER2 receptors - common and effective drug targets in other types of breast cancer. These cancers account for one quarter of all breast cancers, and have a very poor prognosis.

There has been considerable success in targeting gene mutations with specific drugs in other cancers, and so the RATHER project team are aiming to find other possible drug targets, by focusing on protein kinases such as PI3K, the protein inhibited by the novel investigational drug. Taselisib (a PI3K inhibitor) has been developed by Genentech (a member of the Roche Group), and is an isoform-specific inhibitor of the protein PI3K. Genes encoding PI3K are often mutated in breast cancer, particularly in ILC, suggesting that targeting these genes could effectively halt the growth of cancers that are 'driven' by kinases.

Now that the dose escalation part of the POSEIDON trial has been completed, we look forward to opening the randomized Phase II part of the trial later this year to assess its effectiveness at treating hormone receptor-positive (HER2-negative) breast cancer patients. It is expected that phase II will be completed by the end of 2017, with nearly 300 patients from several European countries including the Netherlands, UK, Spain and France participating in the trial.

The joint leaders of the POSEIDON clinical trial, and members of the RATHER program, Prof. Sabine Linn (Netherlands Cancer Institute) and Dr. Richard Baird (University of Cambridge, UK), said "we are delighted that recruitment to the POSEIDON trial is going so well; the combination of taselisib with endocrine therapy is an important new therapeutic approach to test for patients with hormone-driven advanced breast cancer".

The Coordinator of the RATHER project, Prof. William Gallagher (University College Dublin, Ireland), emphasized the importance of this clinical trial and ongoing research into breast cancer, saying "This investigator-led clinical trial provides an exciting opportunity to further extend the arsenal of therapeutic weapons against breast cancer and, importantly, in a highly targeted way. Indeed, this ground-breaking clinical trial is a prime example of the prevalence and power of personalized cancer medicine".

The POSEIDON clinical trial is funded by RATHER, EurocanPlatform (another EU-funded collaborative project), the Netherlands Cancer Institute, and by Genentech.

About the RATHER Project: The main aim of RATHER (www.ratherproject.com) is to find new drug targets for two aggressive types of breast cancer, for which there are currently a lack of effective therapies. RATHER is a collaboration between 8 European partners - 6 academic institutions, in Ireland (University College Dublin), the UK (Cambridge University), The Netherlands (Netherlands Cancer Institute), France (Institut Curie), Sweden (Lund University) and Spain (Vall d'Hebron Hospital), and 2 SMEs, based in Ireland (OncoMark) and The Netherlands (Agendia). Funding: The RATHER project is funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 258967.

Contact info: Prof. Sabine Linn, POSEIDON trial chief investigator, Netherlands Cancer Institute (NKI), Amsterdam, {s.linn AT nki.nl}; Dr. Richard Baird, POSEIDON trial co-investigator, University of Cambridge, UK, {richard.baird AT medschl.cam.ac.uk}; Prof. William Gallagher, RATHER coordinator, University College Dublin, Ireland, {william.gallagher AT ucd.ie}

End of Press Release.
--------------

POSEIDON trial: Click here for POSEIDON trial info from clinicaltrials.gov

Title: "Phase I/Prospective Randomized Phase II Trial of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alone."
Estimated Enrollment: 32
Study Start Date: November 2014
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Note: Poseidon is a small trial of 32 ILC patients and only available in Europe.

However, the PI3K inhibitor: Taselisib (also known as: GDC-0032) is also being used in a different clinical trial, called the SANDPIPER trial. This larger 600 patient trial includes a number of US-based trial sites.
Stage 4 ILC women in the U.S. have an opportunity to participate in this Sandpiper trial using a targeted therapy (that in theory) works against ILC. Here's the Sandpiper info:

SANDPIPER trial: Click here for SANDPIPER trial info from clinicaltrials.gov

Title: "A Study of Taselisib + Fulvestrant versus Placebo + Fulvestrant In Patients With Advanced or Metastatic Breast Cancer Who Have Disease Recurrence or Progression During or After Aromatase Inhibitor Therapy"
Estimated Enrollment: 600
Study Start Date: April 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

* Finally, neither of these two trials mentions the word "Lobular" anywhere in the clinicaltrials.gov trial page, which defies all logic.
Unless your Oncologist knows about this European consortium called "RATHER" and their ILC research, chances are they don't have a clue that these trials exist. Be your own advocate!

I found this statement to be a surprise as well. It could be a journalistic error, as they were describing ILC and TN in the same paragraph.
Most agree that ILC tends to be indolent, but if this organization feels it's aggressive, then so be it.
Historically, there has never been a sense of urgency to understand ILC. Perhaps this group will pave the way to better therapies and threads like "ILC - The Odd One Out" or Lehmann's sobering editorial, among others, won't have to be written.

I'm thankful that we're at the point where the needle of progress is finally moving forward, as evident by these recent developments:

- The TCGA ILC working group announced results from the ILC molecular analysis revealing three subtypes.
[reactive-like; proliferative; immune-related]
- This European based "RATHER" consortium may be a good source of potential ILC targeted therapies.
- RATHER has their Phase 2 ILC trial evaluating a PI3K inhibitor (~50% of ILC has PI3K pathway activation) by using Genetech's (Roche) PI3K inhibitor called Taselisib (GDC-0032). I just realized there are 8 clinical trials utilizing the PI3K inhibitor, Taselisib (GDC-0032). Click here to see them all. The Stage 4 SANDPIPER trial is included.
- The University of Pittsburgh has launched the ILC Biomarker trial. We need "newly diagnosed" patients for this.
- The Derkson lab, an ILC research lab in the Netherlands, developed the first working ILC mouse model, which will be useful to ILC scientists.
- The first international ILC Symposium will be happening next year (September 2016) in Pittsburgh, Pennsylvania.