Phase I study of xentuzumab and abemaciclib
- Conditions
- Advanced/metastatic solid tumourspre-/peri-/post- menopausal locally advanced/metastatic hormone receptor-positive HER2-negative breast cancermetastatic non-small cell lung cancer
- Registration Number
- JPRN-jRCT2080223555
- Lead Sponsor
- ippon Boehringer Ingelheim Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 148
Cohort A (Solid Tumours)
* Patient must be able to swallow oral capsules
* Male or female patients >= 18 years (>=20 years for Japan only) at screening willing and able to use highly effective methods of birth control per ICH M3
* 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
Cohort B, C, D (dose finding), F, D1 and D2 (Breast Cancer):
* Patient must be able to swallow oral capsules.
* Women >= 18 years (>=20 years for Japan only) at screening who have postmenopausal status.
* Histologically or cytologically proven diagnosis of breast cancer with evidence of locally advanced not amenable to resection or radiation or metastatic disease
* HR+ (local lab results at screening or at the time of diagnosis)
* HER2 negative (local lab results at screening or at the time of diagnosis)
* Previous adjuvant and neoadjuvant chemotherapy is permitted. 0-2 prior lines of chemotherapy for the metastatic setting are allowed (except Cohorts D1 and D2).
* At least 1 evaluable 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. For Cohort F only: patients should have at least one measurable lesion.
* Cohort B, C, D (dose finding), F: Must be eligible for the corresponding hormonal therapy. For Cohorts B and C previous treatment with fulvestrant or exemestane is allowed. For Cohort D (dose finding) and F prior therapy with non-steroidal aromatase inhibitors (anastrozole, letrozole) or exemestane are permitted.
* Cohort F only: Postmenopausal with locally advanced or metastatic HR+ breast cancer and refractory to aromatase inhibitor therapy and CDK4/6 inhibitor treatment for locally advanced or metastatic breast cancer. No prior treatment with everolimus is allowed.
For Cohorts D1 and D2 only:
* Have either measurable disease or non-measurable bone only disease.
* No more than one prior line of endocrine therapy for metastatic disease is allowed.
* Progression after endocrine therapy is required (see section 3.3.2)
* For cohort D1 (visceral disease) patient must have at least one documented visceral metastasis (i.e.: lung, liver, pleural, peritoneal, malignant pleural effusion and malignant peritoneal effusion involvement) (see section 3.1.); for cohort D2 (non-visceral disease), patient must not have any visceral metastasis.
Cohort E (NSCLC):
* Patient must be able to swallow oral capsules.
* Male or female patients >= 18 years (>=20 years for Japan only) at screening willing and able to use highly effective methods of birth control per ICH M3
* Histologically or cytologically confirmed diagnosis of stage IV NSCLC.
* The participant must have progressed after platinum-based chemotherapy AND immunotherapy (unless deemed inappropriate candidates for immunotherapy by their treating physician) AND have received 1 or a maximum of 2 other prior chemotherapy for advanced and/or metastatic disease OR must be judged by the physician as ineligible for further standard second-line chemotherapy. Prior treatment with epidermal growth factor re
All cohorts:
* 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.
* 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 anti CDK agents (except in cohort F)
* Prior radiotherapy to >=25% of bone marrow regardless of when it was received
* Unresolved treatment related toxicity from prior therapy of > CTCAE grade 1at study entry (except for stable sensory neuropathy <= CTCAE grade 2 and alopecia).
* Previous treatment with IGF-1R targeting compounds.
* Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease, as indicated by clinical symptoms, cerebral oedema, and/or progressive growth. History of CNS metastases or cord compression are eligible if they have been definitively treated (e.g. radiotherapy, stereotactic surgery) and are clinically stable, off anticonvulsants and steroids for at least 4 weeks. Patients with brain metastases are eligible if they are asymptomatic, completed radiotherapy for at least 4 weeks, or are on a stable dose of steroids for at least 4 weeks. Patients are not eligible if they have spinal cord compression (except Cohorts D1 and D2)
* Inadequate bone marrow reserve or organ function
* 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 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 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.
* Have active bacterial or fungal (that is, requiring intravenous [IV] antibiotics or therapy at time of initiating study treatment), and/or known viral infection
* 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. (See Appendix 10.1)
* Cohort F: prior treatment with everolimus.
For Cohorts D1 and D2 only:
* Have received prior treatment with chemotherapy (except for neoad
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method