PALbociclib CoLlaborative Adjuvant Study (PALLAS)

• ClinicalTrials.gov Identifier: NCT02513394
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2015
• Results First Posted: April 13, 2022
• Last Update Posted: May 25, 2023
• Sponsor: Alliance Foundation Trials, LLC.
• Collaborators: Austrian Breast & Colorectal Cancer Study Group; NSABP Foundation Inc; PrECOG, LLC.; Breast International Group; Pfizer
• Information provided by (Responsible Party): Alliance Foundation Trials, LLC.

Tracking Information

• First Submitted Date: July 29, 2015
• First Posted Date: July 31, 2015
• Results First Submitted Date: February 1, 2022
• Results First Posted Date: April 13, 2022
• Last Update Posted Date: May 25, 2023
• Study Start Date: August 2015
• Actual Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 21, 2022)

Invasive Disease Free Survival (iDFS) [ Time Frame: 4 years ]

Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.

Original Primary Outcome Measures (submitted: July 30, 2015)

Invasive Disease Free Survival (iDFS) [ Time Frame: The expected study duration to primary analysis of iDFS is 4.8 years ]

To compare invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC).

Current Secondary Outcome Measures (submitted: March 21, 2022)

• Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin. [ Time Frame: 4 years ]
  Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
• Distant Recurrence-free Survival (DRFS) [ Time Frame: 4 years ]
  Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported.
• Overall Survival (OS) [ Time Frame: 4 years ]
  Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first.
• Locoregional Recurrences-free Survival (LRRFS) [ Time Frame: 4 years ]
  Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first.

Original Secondary Outcome Measures (submitted: July 30, 2015)

To compare the safety of 2 years of palbociclib with adjuvant endocrine therapy versus adjuvant endocrine therapy alone. (distant recurrence-free survival (DRFS), locoregional recurrences-free survival (LRRFS), and overall survival (OS) [ Time Frame: The expected study duration to primary analysis of iDFS is 4.8 years ]

To compare the following endpoints: iDFS excluding second primary cancers of non-breast origin, distant recurrence-free survival (DRFS), locoregional recurrences-free survival (LRRFS), and overall survival (OS).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PALbociclib CoLlaborative Adjuvant Study
• 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

Brief Summary

This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC).

The purpose of the PALLAS study is to determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer. Assessment of a variety of correlative analysis, including evaluation of the effect of palbociclib in genomically defined tumor subgroups, is planned.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Palbociclib
• Drug: Standard Adjuvant Endocrine Therapy

Study Arms

• Experimental: Arm A
  Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.
  Interventions:

  • Drug: Palbociclib
  • Drug: Standard Adjuvant Endocrine Therapy
• Arm B
  Standard adjuvant endocrine therapy for a duration of at least 5 years.
  Intervention: Drug: Standard Adjuvant Endocrine Therapy

Publications *

• Mayer EL, Fesl C, Hlauschek D, Garcia-Estevez L, Burstein HJ, Zdenkowski N, Wette V, Miller KD, Balic M, Mayer IA, Cameron D, Winer EP, Ponce Lorenzo JJ, Lake D, Pristauz-Telsnigg G, Haddad TC, Shepherd L, Iwata H, Goetz M, Cardoso F, Traina TA, Sabanathan D, Breitenstein U, Ackerl K, Metzger Filho O, Zehetner K, Solomon K, El-Abed S, Theall KP, Lu DR, Dueck A, Gnant M, DeMichele A. Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03). J Clin Oncol. 2022 Feb 10;40(5):449-458. doi: 10.1200/JCO.21.01918. Epub 2022 Jan 7.
• Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, Hernando Fernandez de Aranguiz B, Haddad TC, Perello A, Bellet M, Fohler H, Metzger Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL; PALLAS groups and investigators. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022 Jan 20;40(3):282-293. doi: 10.1200/JCO.21.02554. Epub 2021 Dec 7.
• Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2021 Feb;22(2):212-222. doi: 10.1016/S1470-2045(20)30642-2. Epub 2021 Jan 15.
• Dieras V, Rugo HS, Schnell P, Gelmon K, Cristofanilli M, Loi S, Colleoni M, Lu DR, Mori A, Gauthier E, Huang Bartlett C, Slamon DJ, Turner NC, Finn RS. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. J Natl Cancer Inst. 2019 Apr 1;111(4):419-430. doi: 10.1093/jnci/djy109.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 6, 2020): 5796
• Original Estimated Enrollment (submitted: July 30, 2015): 4600
• Estimated Study Completion Date: September 2025
• Actual Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed informed consent prior to study specific procedures.
• Age ≥18 years (or per national guidelines).
• Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer
• Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-.
• Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer.
• Patients must have undergone adequate (definitive) breast surgery for the current malignancy.

FFPE tumor tissue block must be confirmed to be received at the central sample repository prior to randomization.

• ECOG performance status 0-1.
• Patients must be able and willing to swallow and retain oral medication.
• Serum or urine pregnancy test must be negative in premenopausal women within 14 days of randomization, or in women with amenorrhea of less than 12 months at time of randomization.
• Patients who received neo/adjuvant therapy must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects.
• Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be after last dose of radiotherapy and must have sufficient resolution of side effects.
• Patients must have sufficient resolution of any surgical side effects (no active wound healing complications).

-Patients must either be initiating or have already started adjuvant hormonal treatment. -

• Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy.
• Absolute neutrophil count ≥ 1,500/µL
• Platelets ≥ 100,000/ mm3
• Hemoglobin ≥ 10g/dL
• Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
• Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN.
• Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.

Exclusion Criteria:

• Concurrent therapy with other Investigational Products.
• Prior therapy with any CDK inhibitor.
• Patients with Stage I or IV breast cancer are not eligible.
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
• Patients receiving any medications or substances that are potent inhibitors or inducers of
• CYP3A isoenzymes within 7 days of randomization.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• Pregnant women, or women of childbearing potential without a negative pregnancy test within 14 days prior to randomization.
• Patients with a history of any malignancy are ineligible
• Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy.
• Patients on antiretroviral therapy.
• Patients with clinically significant history of any chronic liver disease.
• Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02513394
• Other Study ID Numbers: AFT-05; ABCSG 42 ( Other Identifier: ABCSG GmbH ); BIG 14-03 ( Other Identifier: Breast International Group ); 2014-005181-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alliance Foundation Trials, LLC.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alliance Foundation Trials, LLC.
• Original Study Sponsor: Same as current

Collaborators

• Austrian Breast & Colorectal Cancer Study Group
• NSABP Foundation Inc
• PrECOG, LLC.
• Breast International Group
• Pfizer

Investigators

• Principal Investigator: Suzanne George, MD; Alliance Foundation Trials, LLC.
• Principal Investigator: Erica Mayer, MD; Dana-Farber Cancer Institute
• Principal Investigator: Angela DeMichele, MD; University of Pennsylvania
• Principal Investigator: Michael Gnant, MD; ABCSG, Medical University Vienna

• PRS Account: Alliance Foundation Trials, LLC.
• Verification Date: April 2023