Palbociclib in Molecularly Characterized ER-positive/HER2-negative Metastatic Breast Cancer

NCT02536742 | Completed Phase 2 Results DMC

• 3 other identifiers: IBCSG 53-14 / BIG 14-042014-005387-15WI198393
• Study Type: interventional
• Target: 124
• Locations: 3 countries
• Sites: 19

Brief Summary

This international, multicenter, prospective single arm Phase II biomarker discovery clinical trial with the primary objective of assessing the association of PFS with gene mutations, gene copy number aberrations and gene signatures in post-menopausal women with hormone receptor positive, HER2-negative metastatic or locally relapsed breast cancer whose disease has progressed after prior adjuvant endocrine therapy or one line systemic treatment, i.e., endocrine treatment or chemotherapy, administered for metastatic disease.

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer; Metastatic; HER2 negative; Palbociclib

Outcome Measures

Primary Outcomes (1)

• Number of Participants With and Without Progression Free Survival (PFS) Events

  Time from treatment initiation until documented disease progression according to RECIST 1.1 or death, whichever occurs first

  Maximum 36 months

Secondary Outcomes (2)

• Best Overall Response

  From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.

• Best Overall Response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD)

  From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.

Study Arms (1)

Experimental

EXPERIMENTAL

Palbociclib plus Fulvestrant

Drug: Palbociclib; Drug: Fulvestrant

Interventions

Palbociclib DRUG

125 mg, orally, daily for 3 weeks followed by 1 week off; repeated at every 28 days cycle until progression, lack of tolerability, or patient declines further protocol treatment.

Also known as: PD-0332991, Ibrance

Experimental

Fulvestrant DRUG

500mg, intramuscularly on days 1 and 15 of cycle 1, then on day 1 (+/- 3 days) of every 28 days cycle until progression, lack of tolerability, or patient declines further protocol treatment.

Also known as: Faslodex

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female gender
• Age ≥ 18 years
• Postmenopausal, defined as women with:
• Prior bilateral surgical oophorectomy; or
• Amenorrhea and age ≥ 60 years; or
• Age \< 60 years and amenorrhea for 12 or more consecutive months in the absence of alternative pathological or physiological cause and FSH and serum estradiol levels within the laboratory's reference ranges for postmenopausal women.
• Endocrine resistant disease, defined as one of:
• Relapse while on adjuvant endocrine therapy;
• Relapse within 12 months after completion of adjuvant endocrine therapy;
• Progression of disease under first line endocrine therapy for metastatic and/or loco-regionally advanced breast cancer.
• Note: Patient may have received one prior chemotherapy for advanced or metastatic breast cancer.
• ER positive tumor and HER2-negative tumor, as assessed locally
• ECOG Performance Status 0-1.
• Measurable or non-measurable but evaluable disease according to RECIST 1.1.
• Written Informed Consent (IC) for screening procedures.

You may not qualify if:

• Prior use of fulvestrant or any CDK inhibitor.
• More than one prior line of chemotherapy for metastatic or locally relapsed disease.
• Previous or current non-breast malignancies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA functional classification ≥3), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
• QTc exceeding 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
• Uncontrolled electrolyte disorders that can reinforce the QT-prolonging effect of the drug (e.g., hypocalcemia, hypokalemia, hypomag¬nesemia).
• Known history of HIV seropositivity. HIV screening is not required at baseline.
• Uncontrolled diabetes defined as HbA1c level \> 7.5%.
• Concurrent disease or familial, sociological or geographical condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient's safety.
• Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of Informed Consent.
• Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant.
• Treatment with an investigational agent in the 4 weeks before enrollment.
• Concurrent treatment with any of the drugs not permitted
• Adverse events (except alopecia) from previous systemic cancer therapy, radiotherapy or surgery have not recovered to CTCAE v4.0 grade 1 or resolved prior to enrollment.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Breast International Group: collaborator

Study Sites (19)

Sint-Augustinus

Antwerp, 2610, Belgium

Location

Institut Jules Bodet

Brussels, 1000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

CHU Liege

Liège, Belgium

Location

Clinique St. Elizabeth

Namur, 5000, Belgium

Location

Ospedali degli Infermi, S.O.C. Oncologia

Biella, 13879, Italy

Location

Ospedale Centrale Bolzano, Medical Oncology

Bolzano, Italy

Location

IRCCS San Martino University Hospital

Genova, Italy

Location

Mater Salutis Hospital AULSS 21 della Regione Veneto

Legnago, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Istituti Clinici Scientifici Maugeri, Medical Oncology Unit

Pavia, 27100, Italy

Location

Azienda USL4 Prato

Prato, Italy

Location

Velindre NHS Trust

Cardiff, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Singleton Hospital

Swansea, United Kingdom

Location

Royal Cornwall

Truro, United Kingdom

Location

Related Publications (5)

• Mittendorf EA, Liu Y, Tucker SL, McKenzie T, Qiao N, Akli S, Biernacka A, Liu Y, Meijer L, Keyomarsi K, Hunt KK. A novel interaction between HER2/neu and cyclin E in breast cancer. Oncogene. 2010 Jul 8;29(27):3896-907. doi: 10.1038/onc.2010.151. Epub 2010 May 10.

  PMID: 20453888 BACKGROUND

• Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.

  PMID: 25524798 BACKGROUND

• Turner NC, Ro J, Andre F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. doi: 10.1056/NEJMoa1505270. Epub 2015 Jun 1.

  PMID: 26030518 BACKGROUND

• Di Leo A, Malorni L. Polyendocrine treatment in estrogen receptor-positive breast cancer: a "FACT" yet to be proven. J Clin Oncol. 2012 Jun 1;30(16):1897-900. doi: 10.1200/JCO.2012.41.7394. Epub 2012 Apr 30. No abstract available.

  PMID: 22547606 BACKGROUND

• Malorni L, Tyekucheva S, Hilbers FS, Ignatiadis M, Neven P, Colleoni M, Henry S, Ballestrero A, Bonetti A, Jerusalem G, Papadimitriou K, Bernardo A, Seles E, Duhoux FP, MacPherson IR, Thomson A, Davies DM, Bergqvist M, Migliaccio I, Gebhart G, Zoppoli G, Bliss JM, Benelli M, McCartney A, Kammler R, De Swert H, Ruepp B, Fumagalli D, Maibach R, Cameron D, Loi S, Piccart M, Regan MM; International Breast Cancer Study Group; Breast International Group and PYTHIA Collaborators. Serum thymidine kinase activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with palbociclib and fulvestrant. Eur J Cancer. 2022 Mar;164:39-51. doi: 10.1016/j.ejca.2021.12.030. Epub 2022 Feb 13.

  PMID: 35172272 DERIVED

Related Links

• Sponsor

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

palbociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Head Trial Activities and Deputy Director: Dr. Heidi Roschitzki-Voser
• Organization: International Breast Cancer Study Group

heidi.roschitzki@ibcsg.org

+41 31 511 94 00

Study Officials

• Luca Malorni, MD PhD

  USL4 Hospital of Prato, Italy

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 1, 2015
• Study Start: August 30, 2016
• Primary Completion: August 28, 2020
• Study Completion: December 22, 2022
• Last Updated: February 26, 2024
• Results First Posted: February 26, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7); BE (7); GB (5)