ILC Clinical Trials - official thread

ILC is chronically understudied and poorly understood. For decades the dogma prevailed that ILC was little different than IDC. Treatment protocols for ILC have (and still are) been based on Clinical Trials that are heavily weighted with IDC patients (at best, no more than ~20% of trial participants are ILC). Extrapolating clinically relevant info from this minority representation is a problem and histology (ILC vs. IDC) subtype analysis is rarely done. Now that numerous large research studies have elucidated on histology differences, we are at an apex where science can begin to explore therapies that cater to the unique characteristics that define ILC and generate better patient outcome.

Science advances with clinical trial participation. Knowledge gained through trials leads to better treatment.
In 2015, for the first time in human history, two clinical trials focused on ILC were launched.
A third clinical trial that encourages ILC patient enrollment was announced in May 2016. It's not much, but these three clinical trials are a start.
The purpose of this thread is to encompass all ILC trials. It will be updated as new trials are launched.

1. ILC Biomarker Clinical Trial
"A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer".
Source: https://clinicaltrials.gov/ct2/show/NCT02206984
Sponsor: University of Pittsburgh - Magee-Womens Hospital of UPMC in Pittsburgh, Pennsylvania, USA.

Estimated Enrollment: 150
Study Start Date: August 2015
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Locations open and recruiting:
USA, Pennsylvania, Pittsburgh - Magee-Womens Hospital of UPMC (Primary site)
USA, Alabama, Birmingham - UAB Comprehensive Cancer Center
USA, California, San Francisco - UCSF
USA, Illinois, Chicago - Univ. of Chicago Medical Center
USA, Minnesota, Rochester - Mayo Clinic
USA, New York, Bronx - Albert Einstein College of Medicine
USA, North Carolina, Chapel Hill - Univ. of North Carolina at Chapel Hill
USA, Texas, Houston - MD Anderson
USA, Texas, Houston - Baylor College of Medicine
USA, Washington, Seattle - SCCA / Fred Hutch

Other proposed locations for Trial participation include:
- University of Alabama in Tuscaloosa, Alabama
- Dana Farber in Boston, Massachusetts
- an institution in Indiana (more details needed).

Additional Notes: This trial is focused on Postmenopausal patients who were "just diagnosed" and have NOT had surgery yet.
This is a pre-surgical "window" Trial to identify Biomarkers of endocrine response in ILC.
They will treat patients during the ~3 week period between initial diagnosis and surgery, using one of three standard endocrine therapies [Tamoxifen or Arimidex or Faslodex], and then compare Biomarkers at pre-therapy (diagnosis) against post-therapy (surgery). The goal is to assess how ILC tumors are responding to the different endocrine therapies.

Press Release: wwww.upmchamot.com/media/NewsReleases/2015/Pages/junkowitz-ilc-trial.aspx

If anyone with ILC expects progress, it's crucial that new ILC patients (who have NOT had surgery yet) enroll in this trial.
Only new patients who are Stage I through Stage III are eligible.
The pace of science is often slow. A common bottleneck that prevents research progress is lack of trial participation. It's important that patients are aware of this trial. It warrants promotion and advertisement. The sooner patients enroll, the sooner the discoveries are made, the sooner new therapies arrive. I cannot emphasize enough the importance of this trial. It would be disappointing if it were cancelled due to lack of participation.

2. PELOPS Clinical Trial [This is the newest trial and announced in May 2016]
Title: "Palbociclib and Endocrine Therapy for Lobular Breast Cancer Preoperative Study"
Source: https://clinicaltrials.gov/ct2/show/NCT02764541
Sponsor: Dana-Farber Cancer Institute in Boston, Massachusetts, USA.

Estimated Enrollment: 180
Study Start Date: May 2016
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)

Locations open and recruiting:
USA, Connecticut, Stamford - Stamford Hospital
USA, Maine, Brewer - Eastern Maine Medical Center
USA, Massachusetts, Boston - Dana-Farber at St. Elizabeth's Medical Center
USA, Massachusetts, Boston - Beth Israel Deaconess Medical Center
USA, Massachusetts, Boston - Dana-Farber Cancer Institute
USA, Massachusetts, Milford - DF/BWCC at Milford Regional Medical Center
USA, Massachusetts, South Weymouth - DF/BWCC in clinical affiliation with South Shore Hospital
USA, Rhode Island, Providence - Lifespan
USA, Tennessee, Nashville - Sarah Cannon Research Institute
USA, Tennessee, Nashville - Vanderbilt University Medical Center

NOTES:
This is a randomized Phase II study of Palbociclib with Femara versus Femara alone.
Palbociclib (AKA: Ibrance), is a CDK4 / CDK6 inhibitor for the treatment of ER+ / HER2- disease.
This is for:
- For early-stage patients (i.e. Stage I to III)
- For Postmenopausal (or Premenopausal who have done Ovarian suppression or had an Oophorectomy) patients.

Interestingly, a very similar trial called PALLAS (see here: https://clinicaltrials.gov/ct2/show/NCT02513394) was launched last year. PALLAS is a large study of ~5000 patients investigating if Ibrance improves outcome. Like the new PELOPS trial, it's also targeting early stage patients.
These trials are being launched due to the success of the PALOMA-1 trial that showed Ibrance extended survival for advanced staged patients, thus leading to FDA approval of the drug in Feb 2015 for metastatic settings.
Here's an 8 minute video with Dr. Erica Mayer of Dana Farber discussing Ibrance and the PALLAS trial.
http://www.slideshare.net/DanaFarber/new-research-in-treating-erpositive-breast-cancer

3. POSEIDON Clinical Trial (organized by the RATHER consortium in Europe - www.ratherproject.com)
Source: https://clinicaltrials.gov/ct2/show/NCT02285179
Title: "Phase I/Prospective Randomized Phase II Trial of the Safety and Efficacy of Tamoxifen in Combination with GDC-0032 compared with Tamoxifen alone."
Sponsor: The Netherlands Cancer Institute

Estimated Enrollment: 32 (for the Phase I portion)
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)

Locations open and recruiting: Ireland (Dublin), Netherlands (Amsterdam), UK (Cambridge), Spain (Barcelona), France (Paris) and Sweden (Lund).

NOTES:
Phase I is done.
Phase II enrollment is ongoing.
Recent large studies (US-based TCGA and Europe-based RATHER/Jules Bordet) have shown that ~50% of ILC has mutations in at least one of the three key genes of the PI3K pathway (PIK3CA, PTEN, and AKT1). This Trial uses a 2nd generation PI3K inhibitor known as GDC-0032 or Taselisib (developed by Genentech/Roche).
This is for:
- For Metastatic (Stage IV) patients.
- For Postmenopausal or Premenopausal patients.

Interestingly, this second generation PI3K inhibitor (Taselisib) is being used in eight other clinical trials, including the SANDPIPER trial.
SANDPIPER is a Phase III trial enrolling 600 Metastatic Stage IV patients with multiple enrollment locations throughout the USA.

Here's the Sandpiper info:
Source: https://clinicaltrials.gov/ct2/show/study/NCT02340221
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)

* Unfortunately, none of these Taselisib trials (or even the POSEIDON trial) mention the word "Lobular" anywhere in the clinicaltrials.gov trial page, which defies all logic.

4. Immunotherapy Clinical Trial - Code named GELATO (or M17GEL).

This is GREAT news and represents the worlds first Lobular clinical trial using Immunotherapy.
The Netherlands Cancer Institute, in conjunction with Roche Genentech, recently announced a Immunotherapy Clinical Trial [NCT03147040] specifically for metastatic ILC. Code named GELATO (or M17GEL), this trial is a needed step in the evolution towards better therapies. As some know, Immunotherapy drugs have been useful in curing *some* metastatic cancer patients (Melanoma, Lung, Bladder, etc). Early results in "general" Immuno-Oncology breast cancer trials have been modest with no more than ~20% of patients achieving durable responses (Triple Negative patients have benefited the most). Science is just scratching the surface of what's possible with Immunotherapy drugs.
The immunotherapy being used is Atezolizumab (Brand name: Tecentriq). It's a Checkpoint Inhibitor targeting a cell surface protein called PD-L1, which is often over-expressed in cancer. The expression of this protein on the cancer cell tells the immune system to back off. The theory is that Atezolizumab may reverse T-cell inactivation and activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against PD-L1-expressing tumor cells. Basically, it interrupts the communication between the cancer cell and immune cells, thus allowing the T-Cells of our immune system to "wake up" and "recognize" the cancer and attack. Cancer uses many tricks to fool our immune system. In this case, the existence of PD-L1 protein acts as a "Brake" preventing the T-Cells from attacking. Atezolizumab helps release the "brake".

Trial Link: https://clinicaltrials.gov/show/NCT03147040

Estimated Enrollment: 40
Anticipated Study Start Date: July 2017
Estimated Primary Completion Date: July 2019

LOCATIONS (4):
Netherlands
1. Antoni van Leeuwenhoek
Amsterdam, Netherlands
Contact: Marleen Kok, MD +3120512 ext 9111 m.kok@nki.nl
Contact: Ingrid AM Mandjes, MSc +3120512 ext 9111 i.mandjes@nki.nl
Principal Investigator: Marleen Kok, MD

2. UMCG
Groningen, Netherlands
Contact: C Schroder, MD
Principal Investigator: C Schroder, MD

3. Maastricht University Medical Center
Maastricht, Netherlands
Contact: V Tjan-Heijnen, Prof. MD
Principal Investigator: V Tjan-Heijnen, Prof. MD

4. Erasmus Medical Center Cancer Institute
Rotterdam, Netherlands
Contact: A Jager, MD
Principal Investigator: A Jager, MD

5. ROLO CLINICAL TRIAL

As many know, the UK-based ROLO clinical trial for advanced lobular breast cancer was announced in April 2018. It's now on the clinicaltrials.gov website, allowing review of the inclusion/exclusion criteria. This trial exploits the concept of "Synthetic Lethality". In Lobular breast cancer (and HDGC gastric cancer), the CDH1 gene is often mutated causing the loss of the E-Cadherin (E-cad) protein. E-Cad loss might contribute to metastasis. Most cancer therapies work by targeting "over-expression" or "gains" (Herceptin for HER2+ amplification is a good example). However, because E-cad is a tumor suppressor protein and "lost" from the cancer cell, it is not a conventional drug target. The synthetic lethality approach is to target a mutated gene that is over-expressed and interacts with (or relies on) CDH1. If you knock out this other gene associated with CDH1, then you might be able to stop proliferation. In this case, ROS1 is the target. Data suggests that loss of E-cad and ROS1 depend on each other, creating the druggable vulnerability.
For this specific trial, they are combining the ROS1 inhibitor, Crizotinib (Xalkori), with Fulvestrant (Faslodex). It will enroll Pre-menopausal or Post-menopausal women.
Here's the media release from April 2018:
https://breastcancernow.org/breast-cancer-research/our-research-projects/rolo-trial-for-advanced-lobular-breast-cancer
Updates to follow.
Trial Link: https://clinicaltrials.gov/ct2/show/study/NCT03620643

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More to follow... Please let me know if a Trial needs to be added to this list.

Off topic. For those on Facebook, an ILC group was created last year. Feel free to join: www.facebook.com/groups/Lobular