Aug 16, 2015 10:14PM Annette_U wrote:
Thanks, I plan to look into this. I am having a total hysterectomy on September 1- then moving to letrazole. I will ask my Onc about this.
All Topics → Forum: Clinical Trials, Research Studies, News, and Study Results → Topic: PALLAS Trial: Palbociclib (Ibrance) - Stage II & III, ER+, HER2-
Share your research articles, interpretations and experiences here. Let us know how these studies affect you and your decisions.
*Research proposals and/or requests posted here by members have been reviewed and approved by The Moderator Team
Posted on: Aug 16, 2015 04:26PM - edited Apr 1, 2017 02:08PM by JohnSmith
The success with Palbociclib (Ibrance) in the PALOMA-1 trial for advanced staged patients, has led to the Feb 2015 drug approval by the FDA (See PR here). Now investigators are wondering if this drug will help "early stage" patients, so a new clinical trial called PALLAS has launched.
The purpose of the PALLAS study is to determine whether the addition of Palbociclib (Ibrance) to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+ / HER2- Stage 2 and Stage 3 breast cancer.
Official title: "PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer"
Estimated Enrollment: 4600 (this is a large trial)
Study Start Date: August 2015
Estimated Study Completion Date: September 2025
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Palbociclib (Ibrance) is considered a targeted therapy and targets the CDK4 & CDK6 pathways.
Here's a 8 minute video with Dr. Erica Mayer of Dana Farber discussing these Ibrance trials.
There's a very extensive thread discussing Ibrance in the Stage IV section, here.
LOCATIONS: As of MARCH 2017, the following locations are enrolling patients:
- Southern Cancer Center
- University of South Alabama Mitchell Cancer Institute
- Katmai Oncology Group
- Marin Cancer Center
- UCSD Moores Cancer Center
- Cedars Sinai Medical Center
- Kaiser Permanente Oakland
- Palo Alto Medical Foundation (PAMF)
- Kaiser Permanente Roseville
- Kaiser Permanente Sacramento
- Kaiser Permanente Zion (San Diego)
- Sharp Memorial Hospital (San Diego)
- Naval Medical Center (San Diego)
- Kaiser Permanente San Francisco
- UCSF Mount Zion
- Kaiser Permanente San Leandro
- Kaiser Permanente Santa Clara
- Kaiser Permanente South San Francisco
- Stanford Hospital and Clinics (Palo Alto)
- Kaiser Permanente Vallejo
- Kaiser Permanente Walnut Creek
- Hartford Hospital
- Christiana Care Health Services
District of Columbia (Washington DC)
- MedStar Georgetown University Hospital
- George Washington University Medical
- Morton Plant Mease (Clearwater)
- Mayo Clinic-Jacksonville
- Mount Sinai Comprehensive Cancer Center (Miami)
- University of Miami Sylvester
- Cancer Institute of Florida (Orlando)
- Phoebe Putney Memorial Hospital
- Emory University (Atlanta)
- Memorial Health University (Savannah)
- Rush University Medical Center (Chicago)
- University of Illinois Cancer Center
- University of Chicago Medical Center
- Cancer Care Specialist of Central Illinois
- Ingalls Memorial Hospital
- Joliet Oncology Hematology Associates
- Illinois CancerCare-Peoria
- OSF Saint Anthony Medical Center
- Orchard Healthcare Research Inc.
- NorthShore Hematology Oncology-Libertyville
- Carle Cancer Center (Urbana)
- Indiana University
- IU Health Ball Memorial Hospital
- McFarland Clinic PC-William R Bliss
- Physicians' Clinic of Iowa PC-Hematology and Oncology
- Iowa Oncology Research Assoc (Des Moines)
University of Kentucky-Mankey Cancer Center
Ochsner Medical Center Jefferson (New Orleans)
- Eastern Maine Medical Center
- New England Cancer Specialists
- Anne Arundel Medical Center (Annapolis)
- Mercy Medical Center
- Greater Baltimore Medical Center
- MedStar Franklin Square Medical Center
- Medstar Union Memorial Hospital
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Frederick Memorial Hospital
- Peninsula Regional Medical Center
- Holy Cross Hospital
- Tufts Medical Center
- Massachusetts General Hospital
- Dana Farber Cancer Institute
- Beth Israel Deaconess Medical Center
- Lowell General Hospital
- Beth Israel Deaconess Medical Center (Plymouth)
- Saint Joseph Mercy Health System
- Trinity Health Michigan
- Essentia Health (Duluth)
- Mayo Clinic-Rochester
- Coborn Cancer Center
- Metro Minnesota Oncology Research Consortium
- St. Luke's Hospital
- Cancer Research for the Ozarks
- Washington University School of Medicine
- Missouri Baptist Cancer Center
- Mercy Hospital
- New Hampshire Oncology-Hematology PA - Concord
- New Hampshire Oncology-Hematology PA - Hooksett
- Dartmouth Hitchcock Medical Center
- Norris Cotton Cancer Center
- Englewood Hospital and Medical Center
- Hackensack Medical Center
- University of New Mexico Comprehensive Cancer Center
- Montefiore Medical Center
- Roswell Park Cancer Institute
- Bassett Healthcare Network
- Hematology Oncology Associates of Central New York
- Queens Cancer Center of Queens Hospital
- Monter Cancer Center
- New York University Langone Medical Center
- Memorial Sloan Kettering Cancer Center (MSKCC)
- Oneonta FoxCare Center
- SUNY Upstate Medical University
- The Charlotte-Mecklenburg Hospital Authority
- Duke University Medical Center
- Cone Health Cancer Center
- Kinston Medical Specialists
- First Health of the Carolinas
- Rapid City Regional Hospital/Regional Cancer Care Institute
- Cleveland Clinic Cancer Center/Fairview Hospital Moll Pavilion
- Cleveland Clinic
- Ohio State University Comprehensive Cancer Center
- Cleveland Clinic Cancer Center/Hillcrest Hospital
- Cancer Centers of Southwest Oklahoma
- Stephenson Cancer Center
- University of Oklahoma Health Sciences Center Stephenson Cancer Center
- Providence Oncology & Hematology Care Clinic - Eastside
- Hematology & Oncology Associates of Northeastern PA
- Penn State Milton S Hershey Medical Center
- Lancaster General Hospital
- University of Pennsylvania
- Pennsylvania Hospital
- Fox Chase Cancer Center
- Allegheny General Hospital
- University of Pittsburgh Cancer Institute- Hillman Cancer Center
- Reading Hospital (Wyomissing)
- WellSpan Health-York Hospital
- Rhode Island Hospital
- Women & Infants Hospital of Rhode Island (Providence)
- Lexington Medical Center
- Avera Cancer Institute-Aberdeen
- Rapid City Regional Hospital
- Avera Cancer Institute-Sioux Falls
- Vanderbilt University Medical Center
- Meharry Medical College
- Baylor College of Medicine (Houston)
- University of Texas MD Anderson Cancer Center (Houston)
- Doctors Hospital of Laredo
- Huntsman Cancer Institute
- Medical Oncology and Hematology of Northern Virginia
- VCU Massey Cancer Center Dalton Oncology Clinic
- CAMC Cancer Center
- Fox Valley Hematology and Oncology
- Saint Vincent Hospital
- Gundersen Lutheran Health System
- University of Wisconsin Hospital
- Columbia St. Mary's
- Orchard Healthcare Research Inc.
Outside of the US:
Australia, New South Wales
Australia, South Australia
Australia, Western Australia
Page 1 of 1 (26 results)
Posts 1 - 26 (26 total)
Aug 16, 2015 10:14PM Annette_U wrote:
Thanks, I plan to look into this. I am having a total hysterectomy on September 1- then moving to letrazole. I will ask my Onc about this.
Aug 17, 2015 09:11PM mary625 wrote:When do you think they'll be announcing the locations conducting this trial?
Dec 8, 2015 05:17PM - edited Dec 8, 2015 05:18PM by JohnSmith
New info on Palbociclib (Brand name: Ibrance), a CDK4 and CDK6 inhibitor for ER+, HER2-.
Public Release: 8-Dec-2015
Philadelphia, Pennsylvania, USA - Combining the new breast cancer drug palbociclib with paclitaxel (Taxol) shrank tumors in nearly half of ER+ patients, according to new research from the Perelman School of Medicine at the University of Pennsylvania.
The results will be presented Saturday at the 2015 San Antonio Breast Cancer Symposium (Abstract P6-13-08).
A second study (Abstract P4-13-04), to be presented Friday provides new clues to how breast cancer develops resistance to the palbociclib, a common occurrence among many patients who take the drug.
"Results of the first study found that palbociclib and paclitaxel can be safely combined on an alternating dosing schedule," said Angela DeMichele, senior author on the study. "The high response rate we saw suggests this combination may hold benefits for patients over paclitaxel alone. Based on these results, a larger clinical trial to determine the benefits is warranted."
A Complementary Therapy
Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which help drive cell division and are upregulated in most cancers. The researchers suspected that palbociclib's unique mechanism of action may make it a good partner for other breast cancer drugs such as paclitaxel, which kills dividing cells at a certain point in the cell division process (also known as the "cell cycle"). Palbociclib effectively halts the cell cycle before that point, and thus in principle can synchronize cancer cells in a way that makes them more vulnerable to a closely following dose of paclitaxel.
To begin to test this concept in the clinic, DeMichele and colleagues, including lead author Amy S. Clark, MD, treated 27 breast cancer patients with alternating doses of palbociclib - administered daily for several days at a time - and paclitaxel administered once per week. The researchers ultimately settled on an optimal palbociclib dose of 75 mg per day, combined with a standard dose of paclitaxel.
The chief aim of the study was to determine if this alternating dosing of the two drugs is safe enough to use in larger-scale trials. The results suggest this appeared to be the case. Though most participants developed the low-white-blood-cell count condition known as neutropenia, a common side-effect of palbociclib and other chemo drugs, DeMichele says in general it was not dangerous. Some participants had their palbociclib doses lowered as a result of the condition.
Although the trial wasn't designed to test whether the combination is more effective against breast tumors than paclitaxel, the patients' responses were promising. Nearly half showed long term shrinkage or disappearance of detectable tumors. "The partial or complete response rate among the entire population was 12 out of 27, or 44 percent, and four additional patients achieved stable disease for six months or longer," Clark said.
"That seemed better than what we would have expected from paclitaxel alone, but the only way to know the difference for certain is with a randomized clinical trial of the combination versus the single drug," DeMichele said.
The team now hopes to set up such a trial. They also plan a similar trial using a newly developed CDK4/6 inhibitor, Novartis's ribociclib.
Clues to Resistance
In a related study, DeMichele and her colleagues, collaborating with a team at palbociclib's maker Pfizer, looked for molecular clues to how breast cancer develops resistance to the drug. By examining samples taken from a patient through the course of her treatment with palbociclib, the team found that as the tumors became resistant, the cells more than doubled their expression of several cell-cycle-driving genes, including PLK1, TOP2A, CDK1, and BUB1. Lab dish studies of tumor cells that develop resistance to palbociclib revealed similar changes.
The study focused on a Penn Medicine patient who was first diagnosed with breast cancer in 1999. After more than a decade of standard therapies, the patient's cancer was found to have progressed in 2010. As part of an earlier clinical trial, she began treatment with palbociclib. The drug caused the woman's tumor to shrink, and her cancer remained progression-free for nearly three years, until a metastatic skin lesion was detected in 2013.
Notably, the resistant cancer cells did not appear to have lost the activity of the tumor suppressor RB1--a potential mechanism of resistance since the CDK4 and CDK6 enzymes drive cell division in part by suppressing RB1. The analysis also ruled out several other suspected mechanisms including alterations to CDK4/6 genes and estrogen receptor genes.
"It appears that while the drug blocks two important cell-cycle drivers, CDK4 and CDK6, other cell cycle genes can compensate with increased expression levels to enable tumor cells to start dividing again," DeMichele said. "That suggests that we might be able to prevent this resistance by adding a drug that blocks these other cell-cycle drivers."
Jul 29, 2016 10:14AM ALH49 wrote:
JohnSmith -- is your wife participating in the PALLAS trial? I'm thinking of doing it and I'm wondering if anyone else with Stage 2 or 3 breast cancer has started the trial and what they've experienced so far.
Dec 8, 2016 05:42PM - edited Dec 8, 2016 05:43PM by JohnSmith
@ALH49. Sorry for the slow response. No, she's not participating in the PALLAS clinical trial.
Here's some news about the trial and CDK 4/6 inhibitors from San Antonio Breast Cancer Symposium (SABCS)
Dec 8, 2016.
Next Big Thing in ER+ Breast Cancer: For Early-Stage Too?
SAN ANTONIO, TEXAS - Two agents that inhibit cyclin-dependent kinases 4 and 6 (CDK4/6) have yielded unprecedented results in progression-free survival in clinical trials involving postmenopausal women with ER+, HER2- metastatic breast cancer.
One drug, palbociclib (Ibrance, Pfizer), is approved by the US Food and Drug Administration in this metastatic setting, and the other agent, ribociclib (Novartis), is under priority review by regulators for use in the same setting.
Now, new data on the third agent in this class, the still experimental abemaciclib (Eli Lilly), show that the strategy of inhibiting CDK4/6 has effectiveness in even more patients – those with early-stage disease.
In the first randomized neoadjuvant trial of a CDK4/6 inhibitor in early-stage patients, twice-daily abemaciclib, either alone or in combination with anastrozole (Arimidex, AstraZeneca), significantly reduced Ki67 expression after 2 weeks of presurgery treatment in comparison with anastrozole alone. Thus, the three-arm, 161-patient study met its primary endpoint.
"Ki67 is a well-validated surrogate endpoint for disease-free survival," said lead study author Sara Hurvitz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. She spoke at a press conference here at the San Antonio Breast Cancer Symposium (SABCS) 2016.
These new findings are akin to results from two earlier, single-arm neoadjuvant trials with palbociclib and ribociclib that also showed reductions Ki67 levels among patients with early-stage disease. Together, these results raise the question:
Is CDK4/6 inhibition well suited to be a curative therapy for early-stage disease?
Dr Hurwitz wants to find out: "We need to push this into early-stage disease," she told Medscape Medical News concerning adjuvant and neodadjuvant studies.
Echoing other experts, she said the results in metastatic disease are important and represent a new standard.
"It's the biggest thing that's happened in the last decade [in metastatic ER-positive disease]," said Dr Hurvitz, referring to the success of CDK4/6 inhibitors. "It's a very important class of drugs."
Tufia Haddad, MD, a medical oncologist at Mayo Clinic, in Rochester, Minnesota, who is not involved in these clinical trials, is looking forward to more results in early-stage disease.
"We are all very hopeful about this class of drugs in this setting," said Dr Haddad, adding that any improvement in overall survival and progression-free survival will be challenging because results with standard endocrine therapies are already good in these patients with early-stage disease.
The large international PALLAS study addresses this question, said Dr Haddad. Now enrolling patients, the adjuvant trial examines standard endocrine therapy alone or in combination with palbociclib for the treatment of pre- and postmenopausal women with stage II and stage III disease that is HR positive and HER2 negative.
Aditya Bardia, MBBS, MPH, a medical oncologist at the Massachusetts General Cancer Center in Boston, believes that CDK4/6 inhibitors will eventually be used in patients with early-stage disease.
"This is a bit speculative, but I think CDK4/6 inhibition would be effective in the right setting of early-stage disease," said Dr Bardia, who was not involved in this new study.
The right setting for curative use would "probably" be in higher-risk patients in whom endocrine therapy alone is unlikely to be sufficient, he told Medscape Medical News.
However, adverse events are a concern, because the adjuvant setting would involve longer-term use than the metastatic setting, Dr Bardia pointed out.
In the current study of abemaciclib, 55% of patients experienced some grade of diarrhea – and that occurred while the patients were receiving a prophylactic agent, per study design. Also, 37% experienced nausea (all grades). Notably, patients in the study were receiving twice-daily therapy only for up to 4 months. "Now imagine for 5 years, or even 1 year of daily therapy," said Dr Bardia. "This does impact the quality of life," he said.
"These are patients with early breast cancer ― the safety profile is very important," concluded Dr Bardia.
One of the selling points of abemaciclib is that it is associated with much less neutropenia than the other two CDK4 inhibitors, as reported in the literature.
In the current study, grade ≥3 neutropenia was reported in only 8.2% of patients, stated Dr Hurvitz. However, Dr Bardia pointed out that 66% of patients still experienced a decrease in neutrophil count.
At the SABCS press conference, Carlos Arteaga, MD, of the Ingram Cancer Center at Vanderbilt University in Nashville, Tennessee, said that abemaciclib was not just an imitation of the more extensively investigated palbociclib. "This is not like Pepsi-Cola and Coca-Cola," he said.
Dr Hurvitz explained that "this is a fairly unique drug in that it can be given continuously."
She said: "We do not need to take a 1-week or more break every month in order to allow neutrophil recovery," she added, referring to the higher rates of neutropenia seen with the other two agents, with their 3-week-off and 1-week-on regimens.
"During that 1 week off...there is this concern that there will be a rebound in [cancer] cell cycling that may actually promote resistance to this therapy," said Dr Hurvitz. "This is a theoretical benefit of abemaciclib."
- San Antonio Breast Cancer Symposium (SABCS) 2016. Abstract 24-06. Presented December 8, 2016.
Jan 9, 2017 05:57PM Melgirl wrote:
I am on day 10 of this study. Anyone else?
Feb 8, 2017 04:37PM Akaamy2003 wrote:
I was just assigned to the PALLAS trial today. I landed in Arm A (palbociclib/Ibrance), which is both a relief and scary at the same time. I am supposed to start next Tuesday the 14th.
I did not have chemotherapy, even though I had three positive nodes, because of a low oncotype score. I'm currently on tamoxifen but recently started Lupron shots and once we know those are doing their job, I'll switch to anastrozole.
I'm interested to hear from others in this trial and would like to keep in touch and compare notes.
Feb 15, 2017 10:21PM Licata519 wrote:
My tissue is being sent in to see if I qualify.
Feb 20, 2017 06:08PM Licata519 wrote:
I am on the control arm, meaning I don't get the Ibrance. 😢
Feb 20, 2017 06:22PM Hopeful82014 wrote:
Bummer about being on the control arm, Licata :( I hope the knowledge that you're helping others is some small consolation.
I would have liked to do the trial but had done neoadjuvant Femara so didn't qualify. Otherwise, I would have volunteered in a heartbeat. I did get into another trial however but don't know which arm I'm in.
Feb 21, 2017 03:49AM SSInUK wrote:
what is the trial Hopefour? I wanted to do PALLAS too but ineligible
Mar 4, 2017 04:32PM Akaamy2003 wrote:
An update from me: After two weeks on palbo my blood work showed my white blood cells (mainly neutrophils) had gone down too low and I had to stop taking it. The plan is to check again in a week or two and then start me back on a lower dose. The only side effects I noticed during those two weeks was the giant bruise where they took blood, and when I blow my nose, it's bloody. But otherwise I have not noticed any unusual bruising, and I have had no fatigue, nausea, hair loss, or anything like that. I felt pretty much totally normal while on palbo. Fingers crossed my WBC bounce back and I can start again soon.
Mar 7, 2017 04:43PM ArtyMom wrote:
I signed the paperwork to join this study today. They took some blood and will take a sample of my tumor. Then I'll be randomized. I'm also joining the B Well study about fitness after treatment. Glad to feel like I'm helping the cause
Mar 13, 2017 03:35PM cwaechte wrote:
I am also participating in this clinical trial too. After ten days I was told to stop taking the drug because my neutrophils count was too low. Like akaAmy2003, I will have my blood work evaluated again this week to see if I can go back on. I'm hoping they are able to do that, maybe with a lower dosage. Unfortunately, I am feeling extremely exhausted, just can't seem to shake it. Good luck to everyone.
Mar 20, 2017 05:25PM ArtyMom wrote:
I was randomized into the 'taking the drug' arm of the study. Taking more blood and getting the drug on Thursday. Also joining the Bwell study, hoping to get the Fitbit and personal fitness training branch
Mar 20, 2017 08:49PM Akaamy2003 wrote:
Welcome Artymom! I hope we can compare notes. I am on round 2 of palbo now. I had to take a break when my neutrophils went too low, but am back on the 125 dose for now. So far I don't have side effects but my understanding is that they may not really kick in until week 3. I have not made it that far yet! I did notice today that I could not taste my lunch at all, so that could be the palbo. Weird.
I have not heard of the Bwell study. I will ask about it. I'd need to be in the couch potato arm, if there is one :)
Mar 23, 2017 08:18PM ArtyMom wrote:
Took my first palbociclib this morning, kind of excited to see how this goes.
Mar 29, 2017 07:24PM ArtyMom wrote:
this combination of tamoxifen and palbociclib is supposed to make me want to sleep all the time, right
Mar 30, 2017 10:43PM Akaamy2003 wrote:
I think some people do have fatigue. I noticed that the monthly questionnaire for the trial has a lot of questions about fatigue. Also joint pain. I have both but they are from a different disorder, so hard to tell how much of it is palbo.
I had my round 2 blood work and my neutrophils were fine this time. I was sure they would be down because my a** was really dragging that day. I am slightly anemic but not so much so that I need to stop the med.
Apr 1, 2017 01:48PM JohnSmith wrote:
I updated the original post above with new locations that are enrolling patients.
Yesterday, Ibrance (Palbociclib) was granted full FDA approval for use in combination with Letrozole (Femara) in the first-line (frontline setting) for postmenopausal women who have HR+ / HER2- metastatic breast cancer.
Apr 6, 2017 04:06PM ArtyMom wrote:
First check in with DR. Today after two weeks on palbo, keeping me on the drug at same level, said I was doing fabulous except for this cold. One more week on the drug and then one off
Apr 7, 2017 10:48AM - edited Apr 7, 2017 10:49AM by Chickwithstix
I am feeling the same way, Artymom. I just finished round 2. I go to bed feeling tired, and wake up feeling tired. Been feeling like a lump, because, after all, I'm "all done" with my chemo and radiation, right? My blood work is all normal, though.
Apr 9, 2017 02:37PM ArtyMom wrote:
Chick, do you notice any difference when you have your week off? I'm on day 7 of this cold and I'm hoping I get some energy back soon. Missed three days of work last week which is more than when I did my radiation.
Apr 11, 2017 11:12PM Cathy148 wrote:
JohnSmith do you think with the approval of Ibrance there is a need to enter the PALLAS Trial? My doctor has suggested it for me. I just finished radiation and haven't started on my aromatase inhibitor yet but can ask my doctor about letrozole with Ibrance instead of the Trial.
Apr 18, 2017 07:37AM KammyMN wrote:
I'm mid cycle 2 of the PALLAS trial - was randomized to receive the Palbo. White count did take a hit, but still just below normal. I'm tired, fingernails, eye brows and lashes thinned but seem to be rebounding already. One of my kiddos had strep but I (thankfully) did not catch it, so immune system hanging in there somewhat. Biggest problem (likely not specific to Ibrance) is weight loss - so difficult after ovary removal, Letrozole and now Ibrance - ugh! Exercise help me mentally, but I'm pretty sure my estrogen made weight management easier - yikes!
Apr 25, 2017 08:44PM cindysmom wrote:
I'm hoping to join this trial after my radiation is over. I am however concerned due to the fact that I have alot of neuropathy from Taxol. I am also diabetic and hypothyroid. I don't want to make this condition worse. Does anyone know if that would be a side effect nI would need to consider
Page 1 of 1 (26 results)