INGE-B: Study in Women With Advanced Breast Cancer Receiving Palbociclib With AI or Fulvestrant

Sponsor

iOMEDICO AG (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02894398

Collaborator

Pfizer (Industry)

388

Enrollment

Locations

Arm

75.8

Anticipated Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Hormone Receptor Positive Tumor Human Epidermal Growth Factor 2 Negative Carcinoma of Breast	Drug: Palbociclib Drug: Letrozole Drug: Anastrozole Drug: Exemestane Drug: Fulvestrant	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

388 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 6, 2016

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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 Other Names: Ibrance Drug: Letrozole Letrozole will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 2.5mg/daily, oral intake Other Names: Femara Drug: Anastrozole Anastrozole will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 1mg/daily, oral intake Other Names: Arimidex Drug: Exemestane Exemestane will be administered as basic therapy (commercially available tablets, obtained from local pharmacies) as followed: 25mg/daily, oral intake Other Names: Aromasin Drug: Fulvestrant Fulvestrant will be administered as basic therapy (commercially available injection, obtained from local pharmacies) as followed: 500mg/once monthly, intramuscular injection Other Names: Faslodex

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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

Other Names:

Ibrance

Drug: Letrozole

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

Other Names:

Femara

Drug: Anastrozole

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

Other Names:

Arimidex

Drug: Exemestane

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

Other Names:

Aromasin

Drug: Fulvestrant

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

Other Names:

Faslodex

Outcome Measures

Primary Outcome Measures

Clinical Benefit Rate (CBR) [24 weeks after first administration of Palbociclib in combination with AI / fulvestrant]
CBR is defined as complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.

Secondary Outcome Measures

Number of participants with Adverse Events as assessed by CTCAE V4.0 [From Date of Signed informed consent until PD, assessed up to 60 months.]
Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v.4.03), and seriousness
Clinical Benefit Rate (CBR) [48 weeks after first administration of Palbociclib in combination with AI / fulvestrant]
CBR is defined as complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.
Progression-free Survival rate [At 48 weeks (all patients) and 2 years (first-line patients only) after first administration of Palbociclib in combination with AI / fulvestrant]
Follow up 4 years after LPI
Overall Survival rate [At 48 weeks after first administration of Palbociclib in combination with AI / fulvestrant and yearly until EOS, assessed up to 60 months.]
Follow up 4 years after LPI
Time on treatment [From day of first treatment until permanent discontinuation (EOT), assessed up to 60 months.]
Study treatment will be continued until disease progression, intolerable toxicity, death or any other reason.
Dosage [From day of first treatment until EOT, assessed up to 60 months.]
starting dose (mg) adjusted doses (mg)
Adminstration schedule [From day of first treatment until EOT, assessed up to 60 months.]
- dates of administration
Health-related quality of life (QoL) [From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.]
Health-related QoL will be assessed with the FACT-B (Functional Assessment of Cancer Therapy-Breast) questionnaire
Health-related fatigue [From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.]
Fatigue will be assessed with the BFI (Brief Fatigue Inventory) questionnaire
Health-related anxiety and depression [From date of signed informed consent until disease progression or start of next anti-cancer therapy: every 12 weeks, assessed up to 60 months.]
Depression and anxiety will be assessed with the HADS-D (Hospital Anxiety and Depression Scale) questionnaire
Physician's assessment of patient's overall health status and change in health status compared to previous visit [From Screening until disease progression or start of next anti-cancer therapy, assessed up to 60 months.]
Assessed by 2 items at each cycle/at scheduled patient visit

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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
Women with proven diagnosis of advanced, defined as locally advanced inoperable or metastatic, adenocarcinoma of the breast
Hormone-receptor-positive (HR+) disease, defined as estrogen-receptor-positive (ER+) and/or progesterone-receptor-positive (PgR+)
Human epidermal growth factor receptor 2-negative (HER2-) disease (HER2 neg/+ or HER2++ with CISH/FISH neg.)
Pre-/perimenopausal women receiving concomitant therapy with an luteinizing hormone-releasing hormone (LHRH) agonist / ovarian ablation or postmenopausal status
Age ≥18 years
Measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST] or bone-only disease
Patients scheduled for palliative treatment with an combination partner for first- or later-line
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Adequate organ and marrow function
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
Fluent in spoken and written German

Exclusion Criteria:

Prior treatment with any CDK4/6 inhibitor
Prior adjuvant therapy with the respective endocrine combination partner if last intake <12 months prior to entering the study
Prior palliative therapy with the respective endocrine combination partner
More than one prior palliative chemotherapy
1. Known hypersensitivity to letrozole, anastrozole, exemestane, fulvestrant or any of their excipients
Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4 (refer to Appendix 15.4)
Current use of preparations containing St. John's Wort
Participation in other studies involving investigational drug(s) (Phases I-IV) within 2 weeks before the current study treatment begins
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
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
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)
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
Known, not-irradiated CNS metastases

Contacts and Locations

Locations

	Site	City	Country
1	Research Site	Aachen	Germany
2	Research Site	Aschaffenburg	Germany
3		Augsburg	Germany
4	Research Site	Baden-Baden	Germany
5	Research Site	Berlin	Germany
6		Bochum	Germany
7		Bonn	Germany
8	Research Site	Bottrop	Germany
9		Bremerhaven	Germany
10	Research Site	Celle	Germany
11		Dessau	Germany
12	Research Site	Donauwörth	Germany
13	Research Site	Dortmund	Germany
14	Research Site	Dresden	Germany
15	Research Site	Essen	Germany
16	Research Site	Esslingen	Germany
17	Research Site	Frankfurt	Germany
18	Research Site	Freiburg	Germany
19	Research Site	Gerlingen	Germany
20		Goslar	Germany
21		Greifswald	Germany
22	Research Site	Göttingen	Germany
23		Göttingen	Germany
24		Güstrow	Germany
25	Research Site	Gütersloh	Germany
26	Research Site	Halle	Germany
27	Research Site	Hamburg	Germany
28		Homburg	Germany
29		Ilsede	Germany
30		Kaiserslautern	Germany
31	Research Site	Karlsruhe	Germany
32	Research Site	Kassel	Germany
33	Research Site	Krefeld	Germany
34	Research Site	Langen	Germany
35	Research Site	Leer	Germany
36		Luneburg	Germany
37		Lörrach	Germany
38		Lübeck	Germany
39		Mannheim	Germany
40		Minden	Germany
41	Research Site	Mönchengladbach	Germany
42	Research Site	Mühlhausen	Germany
43		Mülheim	Germany
44	Research Site	München	Germany
45		München	Germany
46	Research Site	Münster	Germany
47		Neumünster	Germany
48		Neuruppin	Germany
49		Offenburg	Germany
50		Oldenburg	Germany
51		Passau	Germany
52		Potsdam	Germany
53	Research Site	Recklinghausen	Germany
54	Research Site	Regensburg	Germany
55		Rostock	Germany
56		Saarbrucken	Germany
57		Schorndorf	Germany
58	Research Site	Singen	Germany
59		Speyer	Germany
60		Stade	Germany
61		Stolberg	Germany
62		Stuttgart	Germany
63		Traunstein	Germany
64	Research Site	Ulm	Germany
65		Villingen-Schwenningen	Germany
66		Westerstede	Germany
67	Research Site	Wilhelmshaven	Germany
68		Witten	Germany
69		Würselen	Germany
70		Würzburg	Germany