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

Completed · Phase 1

Conditions studied: Neoplasms, Breast Neoplasms

In brief

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."

Key facts

Study ID

NCT03099174

Run by

Boehringer Ingelheim

People needed

133

Starts

2017-05-04

Expected to finish

2024-05-16

Last updated by the study team

2025-06-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• All Cohorts
• Age ≥ 18 years (≥20 years for Japan only) at screening
• Signed and dated written informed consent in accordance with GCP (Good Clinical Practice ) and local legislation prior to admission to the trial
• WHO/ECOG (World Health Organization / Eastern Cooperative Oncology Group) performance status 0-1 assessed at screening
• Patient must be able to swallow oral capsules or tablets
• Cohort A (Solid Tumours) \& Cohort E (NSCLC):
• Male or female patients ready and able to use highly effective methods of birth control during the study and for 3 weeks following the last dose of abemaciclib per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Women of childbearing potential must have a negative serum pregnancy test at screening.
• Cohort A (Solid Tumours)
• Patients with histologically or cytologically confirmed diagnosis of advanced and/or metastatic, measurable or evaluable, non-resectable solid tumours
• Patients must have received and failed, or have been intolerant to, all treatment known to confer clinical benefit or have no therapeutic options available as deemed appropriate by their treating physician
• Life expectancy ≥ 3 months in the opinion of the investigator assessed at screening;
• Cohorts B, C, D (dose finding, Breast Cancer) \& Cohort D1 and Cohort D2 (Breast Cancer):
• Women who have postmenopausal status due to either surgical/natural menopause or chemical ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin or radiation-induced ovarian suppression.
• - postmenopausal status due to surgical/natural menopause requires at least one of the following conditions:
• prior bilateral oophorectomy
• age ≥ 60 years
• age < 60 years and amenorrheic (in the absence of tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12 months; and follicle-stimulating hormone (FSH) and estradiol within the postmenopausal range as per institutional reference ranges.
• Postmenopausal status due to radiation-induced ovarian suppression must be confirmed by FSH and estradiol level in the postmenopausal range.
• Histologically or cytologically proven diagnosis of breast cancer with evidence of locally advanced disease not amenable to curative resection or metastatic disease
• HR+ (local lab results at screening or, if not available, at the time of diagnosis) To fulfil the requirement of HR+ disease, the primary tumour or metastatic lesion of the breast cancer must express at least one of the hormone receptors (estrogen receptor [ER] or progesterone receptor [PgR]) by immunohistochemistry (IHC). Estrogen receptor and PgR assays are considered positive if there are at least 1% positive tumour nuclei in the sample as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010).
• HER2 negative (local lab results at screening or, if not available, at the time of diagnosis) as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010).
• Cohorts B, C, D (dose finding), F (Breast Cancer):
• Previous adjuvant and neoadjuvant chemotherapy is permitted. 0-2 prior lines of chemotherapy for the metastatic setting are allowed (except Cohorts D1, D2 and F).
• At least 1 lesion (measurable or non-measurable) that can be accurately assessed at baseline with CT or MRI or PET-CT (CT portion of diagnostic quality) and which is suitable for accurate repeated measurement.
• Cohort B, C, D: Must be eligible for the corresponding hormonal therapy (letrozole, anastrozole or fulvestrant). For Cohorts B and C previous treatment with fulvestrant or exemestane is allowed. For For Cohort D, prior therapy with non steroidal aromatase inhibitors (anastrozole, letrozole) or exemestane are permitted.

You may not qualify if…

• All - Cohorts A, B, C, D (dose finding), E and F \& Cohort D1 and Cohort D2 (Breast Cancer):
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
• Previous treatment in this trial
• Currently enrolled in another investigational device or drug study, or less than 21 days since ending another investigational device or drug study(s), or receiving other investigational treatment(s).
• Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study subject or unlikely to complete the trial
• Prior anti-cancer chemotherapy, biological or radiation therapy, androgens, thalidomide, other anticancer agents, or any investigational drug within 21 days (14 days for non-myelosuppressive agents); and/or 4 weeks for immunotherapy, before starting any of the trial drugs.
• Prior radiotherapy to ≥ 25% of bone marrow regardless of when it was received
• Unresolved treatment related toxicity from previous therapy of > CTCAE grade 1 at study entry (except for stable sensory neuropathy ≤ CTCAE grade 2 and alopecia)
• Previous treatment with IGF-1R targeting compounds
• The patient has serious and/or uncontrolled pre-existing medical condition(s) that, in the judgement of the Investigator, would preclude participation in this study, including interstitial lung disease, severe dyspnoea at rest or requiring oxygen therapy.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following: ANC < 1.5 x 10\^9/L, platelets < 100 x 10\^9/L, haemoglobin <90g/L, ALT > 2.5 x ULN or > 5 x ULN in the presence of liver metastases, total bilirubin >1.5 x ULN or >3 x ULN in patients with Gilbert's syndrome, serum creatinine > 1.5 x ULN concurrent with creatinine clearance ≤ 50 mL/min.
• Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis
• Refractory nausea and vomiting, chronic GI diseases, inability to swallow the product, or previous significant bowel resection that would preclude adequate absorption of abemaciclib or resulting in baseline Grade 2 or higher diarrhoea
• Patients with Diabetes Type I or uncontrolled Type II (defined by HgBA1C > 8%).
• Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% of liver involvement in metastases.
• Prior hematopoietic stem cell or bone marrow transplant
• Have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Subjects with controlled atrial fibrillation for >30 days prior to study treatment are eligible.
• Erythropoietin, G-CSF, and GM-CSF are not allowed within 2 weeks prior to study. The primary prophylactic use of G-CSF is not permitted but it may be used to treat treatment emergent neutropenia.
• Have had major surgery (excluding biopsy) < 28 days of the initial dose of any of the study drugs or planned major surgery during study participation.
• Have active bacterial or fungal infection (that is, requiring IV antibiotics or therapy at time of initiating study treatment), and/or known viral infection (for example, human immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen, or hepatitis C antibodies). Screening is not required for enrolment.
• Patients with baseline Grade ≥2 hyperglycaemia or patients with baseline Grade ≥ 2 diarrhoea
• Patients needing treatment with CYP3A4 inhibitors/inducers cannot be included in the trial.
• Cohorts A, B, C, D (dose finding), E and F
• Any documented active or suspected malignancy or history of malignancy, other than the disease under study, within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix or ductal carcinoma in situ (DCIS) if properly treated in opinion of the investigator.
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Men who plan to father a child while in the trial.

Where it is running

• 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
• Tampere University Hospital — Tampere, Finland
• CRST - Clinical Research Services Turku — Turku, Finland
• HOP Jean Minjoz — Besançon, France
• INS Paoli-Calmettes — Marseille, France
• INS Curie — Paris, France
• Ctr Cario — Plerin Sur Mer, France
• Aichi Cancer Center Hospital — Aichi, Nagoya, Japan
• National Cancer Center Hospital East — Chiba, Kashiwa, Japan
• Tokai University Hospital — Kanagawa, Isehara, Japan
• National Cancer Center Hospital — Tokyo, Chuo-ku, Japan
• National Cancer Center — Goyang, South Korea
• Severance Hospital — Seoul, South Korea
• Hospital Vall d'Hebron — Barcelona, Spain
• Hospital Clínic de Barcelona — Barcelona, Spain
• Hospital Duran i Reynals — L'Hospitalet de Llobregat, Spain

Full record on ClinicalTrials.gov

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