Study in Women With Advanced Breast Cancer Receiving Palbociclib With AI or Fulvestrant

NCT ID: NCT02894398

Last Updated: 2023-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 388 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-06
• Study Completion Date: 2023-02-15

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.

Conditions

Breast Cancer; Hormone Receptor Positive Tumor; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Palbociclib+AI or Fulvestrant

Letrozole as first-line or later line, Anastrozole as first-line, Exemestane as first-line, Fulvestrant as first-line or later line after prior endocrine therapy.

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

Capsules (commercially available, obtained from local pharmacies), 125mg daily, 21 days, 7 days off, cycles of 28 days.

Dose reductions: 100mg, 75mg (no change in administration schedule) Number of cycles: until disease progression, intolerable toxicity, death or any other reasons

Letrozole

Intervention Type: DRUG

Letrozole will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 2.5mg/daily, oral intake

Anastrozole

Intervention Type: DRUG

Anastrozole will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 1mg/daily, oral intake

Exemestane

Intervention Type: DRUG

Exemestane will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 25mg/daily, oral intake

Fulvestrant

Intervention Type: DRUG

Fulvestrant will be administered as basic therapy (commercially available injection, obtained from local pharmacies) as followed: 500mg/once monthly, intramuscular injection

Interventions

Palbociclib

Capsules (commercially available, obtained from local pharmacies), 125mg daily, 21 days, 7 days off, cycles of 28 days.

Dose reductions: 100mg, 75mg (no change in administration schedule) Number of cycles: until disease progression, intolerable toxicity, death or any other reasons

Intervention Type: DRUG

Letrozole

Letrozole will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 2.5mg/daily, oral intake

Intervention Type: DRUG

Anastrozole

Anastrozole will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 1mg/daily, oral intake

Intervention Type: DRUG

Exemestane

Exemestane will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 25mg/daily, oral intake

Intervention Type: DRUG

Fulvestrant

Fulvestrant will be administered as basic therapy (commercially available injection, obtained from local pharmacies) as followed: 500mg/once monthly, intramuscular injection

Intervention Type: DRUG

Other Intervention Names

Ibrance; Femara; Arimidex; Aromasin; Faslodex

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

iOMEDICO AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

iOMEDICO AG

Role: STUDY_CHAIR

Freiburg / Germany

Locations

Research Site

Aachen, , Germany

Research Site

Aschaffenburg, , Germany

Augsburg, , Germany

Research Site

Baden-Baden, , Germany

Research Site

Berlin, , Germany

Bochum, , Germany

Bonn, , Germany

Research Site

Bottrop, , Germany

Bremerhaven, , Germany

Research Site

Celle, , Germany

Dessau, , Germany

Research Site

Donauwörth, , Germany

Research Site

Dortmund, , Germany

Research Site

Dresden, , Germany

Research Site

Essen, , Germany

Research Site

Esslingen am Neckar, , Germany

Research Site

Frankfurt, , Germany

Research Site

Freiburg im Breisgau, , Germany

Research Site

Gerlingen, , Germany

Goslar, , Germany

Research Site

Göttingen, , Germany

Göttingen, , Germany

Greifswald, , Germany

Güstrow, , Germany

Research Site

Gütersloh, , Germany

Research Site

Halle, , Germany

Research Site

Hamburg, , Germany

Homburg, , Germany

Ilsede, , Germany

Kaiserslautern, , Germany

Research Site

Karlsruhe, , Germany

Research Site

Kassel, , Germany

Research Site

Krefeld, , Germany

Research Site

Langen, , Germany

Research Site

Leer, , Germany

Loerrach, , Germany

Lübeck, , Germany

Lüneburg, , Germany

Mannheim, , Germany

Minden, , Germany

Research Site

Mönchengladbach, , Germany

Research Site

Mühlhausen, , Germany

Mülheim, , Germany

Research Site

München, , Germany

München, , Germany

Research Site

Münster, , Germany

Neumünster, , Germany

Neuruppin, , Germany

Offenburg, , Germany

Oldenburg, , Germany

Passau, , Germany

Potsdam, , Germany

Research Site

Recklinghausen, , Germany

Research Site

Regensburg, , Germany

Rostock, , Germany

Saarbrücken, , Germany

Schorndorf, , Germany

Research Site

Singen, , Germany

Speyer, , Germany

Stade, , Germany

Stolberg, , Germany

Stuttgart, , Germany

Traunstein, , Germany

Research Site

Ulm, , Germany

Villingen-Schwenningen, , Germany

Westerstede, , Germany

Research Site

Wilhelmshaven, , Germany

Witten, , Germany

Würselen, , Germany

Würzburg, , Germany

Countries

Germany

Other Identifiers

iOM-04318

Identifier Type: -

Identifier Source: org_study_id