This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer
- Conditions
- NeoplasmsBreast Neoplasms
- Interventions
- Registration Number
- NCT03099174
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This is a study in adult patients with different types of cancer. The purpose of this study is to find a safe dose of:
* Xentuzumab in combination with abemaciclib
* Xentuzumab in combination with abemaciclib and hormonal therapies The study also tests whether these medicines make tumours shrink in participants with lung and breast cancer.
Participants can stay in the study as long as they benefit from and can tolerate treatment. All participants get xentuzumab infusions and abemaciclib tablets. Participants who have breast cancer get different types of hormonal therapies in addition to xentuzumab and abemaciclib.
For all participants, the size of the tumour is measured regularly. Doctors also regularly check the general health of the participants."
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 133
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib Xentuzumab Patients with solid tumours received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib Abemaciclib Patients with solid tumours received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole Xentuzumab Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet). Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Abemaciclib Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Abemaciclib Patients with HR+ HER2- breast cancer \& with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Xentuzumab Patients with HR+ HER2- breast cancer \& with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole Abemaciclib Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet). Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole Letrozole Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 2.5 mg Letrozole (once daily film-coated tablet). Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole Xentuzumab Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet). Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole Abemaciclib Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet). Cohort C: Xentuzumab 1000 mg & 150 mg Abemaciclib & 1 mg Anastrozole Anastrozole Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 1 mg Anastrozole (once daily film-coated tablet). Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Xentuzumab Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Fulvestrant Patients with Hormone receptor+ (HR+) Human epidermal growth factor receptor 2 (HER2-) breast cancer received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib Xentuzumab Patients with non-small cell lung cancer (NSCLC) received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Cohort E: Xentuzumab 1000 mg & 150 mg Abemaciclib Abemaciclib Patients with non-small cell lung cancer (NSCLC) received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Xentuzumab Patients with HR+ HER2- breast cancer \& non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Fulvestrant Patients with HR+ HER2- breast cancer \& non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort F: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Abemaciclib Patients with HR+ HER2- breast cancer \& non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Xentuzumab Patients with HR+ HER2- breast cancer \& with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D1: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Fulvestrant Patients with HR+ HER2- breast cancer \& with visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Fulvestrant Patients with HR+ HER2- breast cancer \& with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose). Cohort D2: Xentuzumab 1000 mg & 150 mg Abemaciclib & 500 mg Fulvestrant Abemaciclib Patients with HR+ HER2- breast cancer \& with non-visceral disease received 1000 milligram (mg) Xentuzumab (weekly 10 mg/milliliter intravenous infusion) and 150 mg Abemaciclib (every 12 hours three 50 mg film coated tablets) in a 28-day cycle until disease progression, intolerability of the study medication, or consent withdrawal. Combined with a background therapy of 500 mg Fulvestrant (Faslodex®) (once a month intramuscular injection, with an additional 500 mg dose given two weeks after the first dose).
- Primary Outcome Measures
Name Time Method [Cohort A, B, C & D] Maximum Tolerated Dose (MTD) of Xentuzumab The first treatment cycle, up to 28 days. MTD during the MTD evaluation period (the first 28 day cycle). The MTD is defined as the highest dose with \<25% risk of the true Dose limiting toxicity (DLT) rate \>33%.
DLT: adverse event or laboratory abnormality which 1) is related, probably related or possibly related to study drug and 2) meets any of the following criteria, unless that toxicity can be attributed to cancer progression or to identified etiology:
CTCAE grade (Gr). 3+ hyperglycaemia (\>48 hours), Gr. 4 hyperglycaemia, hematologic toxicity (\>5 days), Gr. 3+ pneumonitis, febrile neutropenia, thrombocytopenia (Gr. 4 any duration, Gr. 3 w/ bleeding), AST/ALT \> 5x ULN or \> (baseline + 4x ULN), Gr. 3+ diarrhoea, nausea, vomiting (\>2 days), skin rash, fatigue/asthenia (\>7 days), Gr. 3-4 hyperlipidaemia (\>2 weeks), Any AE causing 2-week treatment interruption, non-hematologic toxicities Gr. 3+ (except alopecia, infusion-related reaction), Any significant drug related toxicity qualified as DLT.[Cohort A, B, C & D] Number of Patients With DLTs in the MTD Evaluation Period The first treatment cycle, up to 28 days. Number of patients with Dose limiting toxicities in the MTD evaluation period.
Dose limiting toxicity (DLT): adverse event or laboratory abnormality which 1) is related, probably related or possibly related to study drug and 2) meets any of the following criteria, unless that toxicity can be attributed to cancer progression or to identified etiology:
CTCAE grade (Gr). 3+ hyperglycaemia (\>48 hours), Gr. 4 hyperglycaemia, hematologic toxicity (\>5 days), Gr. 3+ pneumonitis, febrile neutropenia, thrombocytopenia (Gr. 4 any duration, Gr. 3 w/ bleeding), AST/ALT \> 5x ULN or \> (baseline + 4x ULN), Gr. 3+ diarrhoea, nausea, vomiting (\>2 days), skin rash, fatigue/asthenia (\>7 days), Gr. 3-4 hyperlipidaemia (\>2 weeks), Any AE causing 2-week treatment interruption, non-hematologic toxicities Gr. 3+ (except alopecia, infusion-related reaction), Any significant drug related toxicity qualified as DLT.[Cohort E] Number of Patients With Objective Response (OR) Up to 26.5 months Objective response (OR) defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 from date of first treatment administration (including run-in for cohort E) until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeter (mm)). For non-target lesions: disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis).
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.[Cohorts D1 and D2] Progression Free Survival (PFS) at 18 Months Up to 18 months. Progression free survival (PFS) rate at 18 month defined as the rate of absence of disease progression or death at the 18th month of treatment, where progression is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.
Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions: Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression).
Reported is the progression free survival rate at 18 months, based on a Kaplan-Meier.[Cohort F] Disease Control (DC) Up to 18.5 months. Disease control (DC) defined as best overall response of complete response (CR) or partial response (PR) or confirmed stable disease (SD) (lasting for at least 24 weeks) or Non-CR/ Non-PD (lasting for at least 24 weeks) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest sum diameters while on study.
- Secondary Outcome Measures
Name Time Method [Cohorts E, D1 and D2] Disease Control (DC) Up to 35.2 months. Disease control (DC) defined as best overall response of complete response (CR) or partial response (PR) or confirmed stable disease (SD) (lasting for at least 24 weeks) or Non-CR/ Non-PD (lasting for at least 24 weeks) where best overall response is defined according to RECIST version 1.1 from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest sum diameters while on study.[Cohorts E, F, D1 and D2] Duration of Objective Response Up to 27.2 months. Duration of objective response defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response.
[Cohorts E, F, D1 and D2] Progression-free Survival (PFS) Up to 33 months. Progression-free survival (PFS) defined as the time from first treatment administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurs earlier.
Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions: Unequivocal progression of existing non-target lesions (Note: the appearance of one or more new lesions is also considered progression).[Cohorts D1, D2 and F] Objective Response (OR) Up to 35.2 months. Objective response (OR) defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 from date of first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeter (mm)). For non-target lesions: disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (\<10mm short axis).
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.[Cohorts E, F, D1 and D2] Time to Objective Response Up to 21.9 months. Time to objective response defined as the time from first treatment administration until first documented complete response (CR) or partial response (PR).
[Cohorts E, F, D1 and D2] Duration of Disease Control Up to 33.1 months. Duration of disease control defined as the time from first treatment administration until the earliest of disease progression or death, among patients with disease control.
Trial Locations
- Locations (30)
University of California Los Angeles
🇺🇸Santa Monica, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Miami
🇺🇸Miami, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Herlev and Gentofte Hospital
🇩🇰Herlev, Denmark
Copenhagen University Hospital, Rigshospitalet
🇩🇰København Ø, Denmark
Docrates Clinic
🇫🇮Helsinki, Finland
HUCH Comprehensive Cancer Center, building 2
🇫🇮Helsinki, Finland
Scroll for more (20 remaining)University of California Los Angeles🇺🇸Santa Monica, California, United States