A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors
- Conditions
- Metastatic renal cell carcinoma (RCC), advanced urothelial carcinoma, advanced gastric (including gastro-esophageal [GEJ]) adenocarcinoma, and metastatic colorectal adenocarcinoma (CRC)MedDRA version: 18.1Level: PTClassification code 10052360Term: Colorectal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003656-40-ES
- Lead Sponsor
- Pharmacyclics LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 189
1. Histologically confirmed:
RCC (clear cell)
Urothelial carcinoma (transitional cell)
Gastric or GEJ adenocarcinoma
K-RAS wild-type EGFR expressing CRC
2. One or more measurable lesions per RECIST 1.1 criteria.
3. The following prior criteria should be followed:
Metastatic RCC: minimum of 1 and maximum of 4 prior regimens, one or more of which must have included a VEGF-TKI
Advanced (locally recurrent and/or metastatic) urothelial carcinoma: minimum of 1 and maximum of 2 prior regimens, one of which must be a cisplatin based regimen
Advanced (locally recurrent and or metastatic) gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must be a fluoropyrimidine based regimen
Metastatic CRC: minimum of 2 and maximum of 4 prior regimens, which must have included both an irinotecan and an oxaliplatin based regimen or unable to tolerate irinotecan chemotherapy
4. Each subject must be assessed by the investigator to be a suitable candidate for treatment with everolimus, docetaxel, paclitaxel or cetuximab, as appropriate according to their type of cancer.
5. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of study drug and agree to use dual methods of contraception during the study and for 1 month following the last dose with study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from this criterion.
6. Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.
Laboratory
7. Adequate hematologic function (independent of transfusion and growth factor support for at least 7 days prior to enrollment, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to enrollment defined as:
Absolute neutrophil count more than 1500 cells/mm3 (1.5 x 109/L)
Platelet count >80,000 cells/mm3 (80 x 109/L)
Hemoglobin >8.0 g/dL
8. Adequate hepatic and renal function defined as:
Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) smaller or equal than 5.0 x upper limit of normal (ULN) if liver metastases, or less than 3 x ULN without liver metastases
Alkaline phosphatase less than 3.0 x ULN or ?5.0 x ULN if liver or bone metastases present
Bilirubin smaler or equal 1.5 x ULN (unless bilirubin rise is due to Gilbert s syndrome or of non-hepatic origin, such as hemolysis) with the exception of patients in the gastric adenocarcinoma cohort where docetaxel is administered, these patients must have bilirubin within normal limits (WNL).
Estimated Creatinine Clearance greater than or equal 30 mL/min (Cockcroft-Gault)
Demographic
9. Men and women greater than or equal 18 years of age
10. Eastern Cooperative Oncology Group (ECOG) performance status 0 1. For subjects with RCC or CRC, an ECOG score of 2, may be acceptable if approved by the medical monitor.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 189
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 189
1. Anticancer therapy (chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 28 days of the first dose of study drug (6 weeks for nitrosureas, mitomycin C, or antibody based therapies)
2. Prior treatment with:
Everolimus or temsirolimus (RCC cohort)
Any taxane (urothelial carcinoma cohort)
Any taxane (gastric adenocarcinoma cohort)
Cetuximab or panitumumab (CRC cohort)
3. Prior radiotherapy to measurable lesion, unless documented progression has occurred post-irradiation
4. Lack of recovery from previous therapeutic radiation (persistence of Grade greater than or equal than 2 radiation-related toxicity), or planned radiation therapy during the study period
Concurrent Conditions
5. Any uncontrolled active systemic infection including any infection requiring systemic IV treatment which was completed minor or equal than 7 days before Cycle 1 Day 1.
6. History of other malignancies, except:
Malignancy treated with curative intent and with no known active disease present for mayor than or equal 3 years before the first dose of study drug and felt to be at low risk for recurrence by investigator
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without current evidence of disease
7. Prior treatment with ibrutinib or other BTK inhibitor
8. ALT and/or AST more than 1.5 x ULN and alkaline phosphatase more than 2.5 x ULN (gastric adenocarcinoma cohort only)
9. Known allergy or hypersensitivity to ibrutinib or any other component of combination therapy, including polysorbate 80 or Cremophor® EL (polyoxyethylated castor oil)
10. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade 0 or 1
11. Known bleeding disorders (eg, von Willebrand?s disease) or hemophilia
12. Grade mayor than or equal 3 sensory peripheral neuropathy
13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
14. Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement)
15. Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV)
Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
16. Major surgery within 4 weeks of first dose of study drug
17. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator s opinion, could compromise the subject s safety or put the study outcomes at undue risk
18. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure, as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
19. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
20. Unable to swallow capsules and/or tablets
21. Concomitant use of warfarin or other Vitamin K antagonists
22. Requires t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method