Clinical trial NCT02894398: Study in Women With Advanced Breast Cancer Receiving Palbociclib With AI or Fulvestrant
Official title: Open-label, Multi-center, sINGlE Arm Clinical Study to Evaluate Efficacy/QoL in Women With HR+, HER2-, Regionally Recurrent or Metastatic Breast Cancer Receiving Palbociclib With an AI or Fulvestrant After Prior Endocrine Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Hormone Receptor Positive Tumor
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Keywords: HR+
HER2-
Locally advanced (inoperable or metastatic) Breast Cancer
Palbociclib
Aromatase inhibitor or fulvestrant
Pre-/perimenopausal receiving LHRH agonist / ovarian ablation
Postmenopausal
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2016-09-09
Enrollment: 388
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and quality of life in women with advanced breast cancer (locally advance inoperable or metastatic adenocarcinoma of the breast), HR+ / HER2-, who are treated with an aromatase inhibitor or fulvestrant as baseline therapy in combination with palbociclib (Ibrance)

Detailed description: This is a prospective, open-label, multi-center, single arm, non-comparative phase II study in women with HR+/HER2- advanced breast cancer receiving palbociclib in addition to an aromatase inhibitor or fulvestrant. The study will take place in Germany (85 study centers).

In total, 360 patients will be enrolled in this study. 6 treatment groups are planned. The study seeks to recruit 60 (58-62) patients per recruitment group. For first-line treatment with palbociclib - and letrozole (Enrollment Group 1), anastrozole (Enrollment Group 2), exemestane (Enrollment Group 3) or fulvestrant (Enrollment Group 4) and 60 (58-62) patients for second- or later-line treatment with palbociclib -and letrozole (Enrollment Group 5) or fulvestrant (Enrollment Group 6). Recruitment will be centrally monitored to allow closure of a respective group as soon as 60 (58-62) patients have been enrolled.

Treatment will be continued until disease progression, intolerable toxicity, death or any other reason. In case a combination partner is discontinued, palbociclib has to be discontinued. In case treatment with palbociclib is stopped, combination partner can be continued according to investigator's discretion. Irrespectively of the combination partner, the discontinuation of palbociclib is defined as end of treatment (EOT) in this study. After EOT the patient enters the follow-up period.

Primary end point is clinical benefit rate 24 weeks after the first study treatment of the patient.

A study independent, decentral, "virtual" biobank will be established. All patients will be asked to give consent for their tumor samples to be used for future investigational research. Study sites will inform the local pathologists about the patient's consent and ask for the tissue sample to be reserved for future analyses. The site is requested to collect contact details of the pathologist storing the tumor sample, the sample's identification number(s), and to document these in the eCRF.

The decision to perform subsequent investigational research studies on collected samples will be based on outcome data from this study or from new scientific findings related to the drug class or disease, as well as reagent and assay availability.

Eligibility criteria: Inclusion Criteria:

1. Personally signed written informed consent prior to beginning protocol specific procedures, including expected cooperation of the patient for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
2. Women with proven diagnosis of advanced, defined as locally advanced inoperable or metastatic, adenocarcinoma of the breast
3. Hormone-receptor-positive (HR+) disease, defined as estrogen-receptor-positive (ER+) and/or progesterone-receptor-positive (PgR+)
4. Human epidermal growth factor receptor 2-negative (HER2-) disease (HER2 neg/+ or HER2++ with CISH/FISH neg.)
5. Pre-/perimenopausal women receiving concomitant therapy with an luteinizing hormone-releasing hormone (LHRH) agonist / ovarian ablation or postmenopausal status
6. Age ≥18 years
7. Measurable disease as per Response Evaluation Criteria in Solid Tumors \[RECIST\] or bone-only disease
8. Patients scheduled for palliative treatment with an combination partner for first- or later-line
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
10. Adequate organ and marrow function
11. Resolution of all acute toxic effects of prior therapy, including radiotherapy Grade \<1 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures
12. Fluent in spoken and written German

Exclusion Criteria:

1. Prior treatment with any CDK4/6 inhibitor
2. Prior adjuvant therapy with the respective endocrine combination partner if last intake \<12 months prior to entering the study
3. Prior palliative therapy with the respective endocrine combination partner
4. More than one prior palliative chemotherapy
5. 5. Known hypersensitivity to letrozole, anastrozole, exemestane, fulvestrant or any of their excipients
6. Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4 (refer to Appendix 15.4)
7. Current use of preparations containing St. John's Wort
8. Participation in other studies involving investigational drug(s) (Phases I-IV) within 2 weeks before the current study treatment begins
9. QTc \> 480 msec on the screening ECG (using the QTcF formula and/or the QTcB (Bazett) formula); history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes
10. High cardiovascular risk, including, but not limited to recent myocardial infarction, severe/unstable angina and severe cardiac dysrhythmias in the past 6 months prior to enrollment
11. Patients with advanced symptomatic, visceral spread, that were at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \[pleural, pericardial, peritoneal\], pulmonary lymphangitis, and over 50% liver involvement)
12. Diagnosis of any second malignancy within the last 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
13. Known, not-irradiated CNS metastases

Primary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: 24 weeks after first administration of Palbociclib in combination with AI / fulvestrant
Secondary outcomes:
measure: Number of participants with Adverse Events as assessed by CTCAE V4.0
timeFrame: From Date of Signed informed consent until PD, assessed up to 60 months.
measure: Clinical Benefit Rate (CBR)
timeFrame: 48 weeks after first administration of Palbociclib in combination with AI / fulvestrant
measure: Progression-free Survival rate
timeFrame: At 48 weeks (all patients) and 2 years (first-line patients only) after first administration of Palbociclib in combination with AI / fulvestrant
measure: Overall Survival rate
timeFrame: At 48 weeks after first administration of Palbociclib in combination with AI / fulvestrant and yearly until EOS, assessed up to 60 months.
measure: Time on treatment
timeFrame: From day of first treatment until permanent discontinuation (EOT), assessed up to 60 months.
measure: Dosage
timeFrame: From day of first treatment until EOT, assessed up to 60 months.
measure: Adminstration schedule
timeFrame: From day of first treatment until EOT, assessed up to 60 months.
measure: Health-related quality of life (QoL)
timeFrame: From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.
measure: Health-related fatigue
timeFrame: From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.
measure: Health-related anxiety and depression
timeFrame: From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.
measure: Physician's assessment of patient's overall health status and change in health status compared to previous visit
timeFrame: From Screening until disease progression or start of next anti-cancer therapy, assessed up to 60 months.
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Research Site
city: Aschaffenburg
country: Germany
facility: Research Site
city: Augsburg
country: Germany
city: Baden-Baden
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
city: Bonn
country: Germany
city: Bottrop
country: Germany
facility: Research Site
city: Bremerhaven
country: Germany
city: Celle
country: Germany
facility: Research Site
city: Dessau
country: Germany
city: Donauwörth
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Esslingen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Gerlingen
country: Germany
facility: Research Site
city: Goslar
country: Germany
city: Greifswald
country: Germany
city: Göttingen
country: Germany
facility: Research Site
city: Göttingen
country: Germany
city: Güstrow
country: Germany
city: Gütersloh
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Homburg
country: Germany
city: Ilsede
country: Germany
city: Kaiserslautern
country: Germany
city: Karlsruhe
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Krefeld
country: Germany
facility: Research Site
city: Langen
country: Germany
facility: Research Site
city: Leer
country: Germany
facility: Research Site
city: Luneburg
country: Germany
city: Lörrach
country: Germany
city: Lübeck
country: Germany
city: Mannheim
country: Germany
city: Minden
country: Germany
city: Mönchengladbach
country: Germany
facility: Research Site
city: Mühlhausen
country: Germany
facility: Research Site
city: Mülheim
country: Germany
city: München
country: Germany
facility: Research Site
city: München
country: Germany
city: Münster
country: Germany
facility: Research Site
city: Neumünster
country: Germany
city: Neuruppin
country: Germany
city: Offenburg
country: Germany
city: Oldenburg
country: Germany
city: Passau
country: Germany
city: Potsdam
country: Germany
city: Recklinghausen
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Rostock
country: Germany
city: Saarbrucken
country: Germany
city: Schorndorf
country: Germany
city: Singen
country: Germany
facility: Research Site
city: Speyer
country: Germany
city: Stade
country: Germany
city: Stolberg
country: Germany
city: Stuttgart
country: Germany
city: Traunstein
country: Germany
city: Ulm
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
city: Westerstede
country: Germany
city: Wilhelmshaven
country: Germany
facility: Research Site
city: Witten
country: Germany
city: Würselen
country: Germany
city: Würzburg
country: Germany
Study officials:
affiliation: Freiburg / Germany
name: iOMEDICO AG
role: STUDY_CHAIR
References: