Overview

This trial is active, not recruiting.

Condition metastatic colorectal cancer
Treatments bax69 + infusional 5-fu/lv, bax69 + panitumumab, bax69 + 5-fu/lv, standard of care
Phase phase 2
Targets KRAS, NRAS, EGFR
Sponsor Baxalta US Inc.
Start date May 2015
End date May 2017
Trial size 112 participants
Trial identifier NCT02448810, 2015-000896-28, 391401

Summary

The purpose of this study is to evaluate the safety and tolerability of BAX69 in combination with 5-fluorouracil (5-FU)/leucovorin (LV) or panitumumab to determine the recommended phase II dose (RP2D) of each combination; and to compare the efficacy between BAX69 in combination with 5-FU/LV for subjects with KRAS or NRAS mutated tumor (mt) or panitumumab, for subjects with KRAS and NRAS wild type tumor (wt) and standard of care (SoC) per investigator choice as third or fourth treatment line in subjects with progressive measurable metastatic colorectal cancer (mCRC).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Subjects stratified according to their mutation status.
bax69 + infusional 5-fu/lv Macrophage Migration Inhibitory Factor Antibody (Anti-MIF)
Study Part 1: Safety Run-in Administered weekly as part of a 4 week treatment cycle Intravenous injection
(Experimental)
Subjects stratified according to their mutation status.
bax69 + panitumumab Imalumab
Study Part 1: Safety Run-in Administered weekly as part of a 4 week treatment cycle Intravenous injection
(Experimental)
Subjects stratified according to their mutation status.
bax69 + 5-fu/lv Imalumab
(Experimental)
Subjects stratified according to their mutation status.
bax69 + panitumumab Imalumab
(Active Comparator)
Subjects stratified according to their mutation status.
standard of care
Investigator's choice Dose according to drug label
(Active Comparator)
Subjects stratified according to their mutation status.Subjects stratified according to their mutation status.
standard of care
Investigator's choice Dose according to drug label Choice includes panitumumab in KRAS &NRAS wt group only

Primary Outcomes

Measure
Occurrence of Dose Limiting Toxicity (DLT)
time frame: 4 weeks
Progression-Free Survival (PFS)
time frame: Approximately 6 months

Secondary Outcomes

Measure
Occurrence of binding and/or neutralizing BAX69 antibodies
time frame: Throughout the study period, approximately 21 months
Incidence and severity of infusion reactions after BAX69
time frame: Throughout the study period, approximately 21 months
Occurrence of serious adverse events (SAEs) and/or treatment-emergent adverse events (TEAEs)
time frame: Throughout the study period, approximately 21 months
Response evaluation according to RECIST v1.1
time frame: Day 28 of Cycle 2 and then every other cycle (each cycle is 28 days), ie Day 56, Day 112, Day 168, Day 224, etc for duration of study participation
Overall survival (OS) defined as time from randomization to death of any cause
time frame: Throughout the study period, approximately 21 months
Quality of Life (QoL) measure - European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire
time frame: Day 1, and at study completion or early discontinuation, should occur 30 (±7) days after the last dose of study treatment.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Provision of a signed informed consent 2. Male and female subjects 18 years of age and older at the time of screening 3. Subjects who progressed after receiving at least 2, but no more than 3, prior SoC treatment lines 4. Anticipated life expectancy >3 months at the time of screening 5. Weight between 40 kg and 180 kg 6. Histologically or cytologically confirmed diagnosis of CRC 7. Metastatic CRC not amenable to surgical resection 8. Known KRAS and NRAS mutation status (if unknown status for either of these genes, and no archival tissues is available, a fresh tumor biopsy will be made) 9. At least 1 measurable lesion as defined by RECIST v1.1 10. ECOG PS of 0-2 11. Adequate hematological function, defined as: 1. Platelet count ≥ 100,000/μL 2. Prothrombin time and activated partial thromboplastin time (aPTT) < 1.5 times the upper limit of normal (ULN) 3. Absolute neutrophil count (ANC) ≥ 1,000/μL 4. Hemoglobin ≥ 9 g/dL, without the need for transfusion in the 2 weeks prior to screening 12. Adequate renal function, defined as serum creatinine ≤ 2.0 times ULN and creatinine clearance > 50 mL/min 13. Adequate liver function, defined as: 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN for subjects without liver metastases, or ≤ 5 times ULN in the presence of liver metastases 2. Bilirubin ≤ 2.0 times ULN, unless subject has known Gilbert's syndrome 14. Adequate venous access 15. For female subjects of childbearing potential, the subject presents with a negative serum pregnancy test at screening and agrees to employ 2 forms of adequate birth control measures, including at least 1 barrier method (eg, diaphragm with spermicidal jelly or foam, or [for male partner] condom) throughout the course of the study and for at least 90 days after the last administration of BAX69. Other acceptable contraceptive measures include birth control pills/patches or intrauterine devices 16. For male subjects, the subject must agree to use adequate contraceptive measures including at least 1 barrier method (eg, condom with spermicidal jelly or foam and [for the female partner] diaphragm with spermicidal jelly or foam, birth control pills/patches, or intrauterine device) and abstain from sperm donation throughout the course of the study and for at least 90 days after the last administration of BAX69 17. Subject is willing and able to comply with the requirements of the protocol. Exclusion Criteria: 1. Known central nervous system metastases 2. Prior malignancy(s) within the past 3 years, with the exception of curatively treated basal or squamous cell carcinoma of the skin, locally advanced prostate cancer, ductal carcinoma in situ of breast, in situ cervical carcinoma and superficial bladder cancer 3. Prior treatment with panitumumab for subjects with KRAS and NRAS wt tumor 4. Residual AE from previous treatment > Grade 1 5. Prior intolerance to fluoropyrimidine for subjects with KRAS or NRAS mut tumor 6. Myocardial infarction within 6 months prior to C1D1, and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication; and/or the subject is at risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long QT syndrome) 7. Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg confirmed upon repeated measures 8. LVEF < 40% as determined by echocardiogram performed at screening or within 90 days prior to C1D1 9. QT/QTc interval > 450 msec, as determined by screening ECG performed no earlier than 1 week before C1D1 10. Prior anti-tumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular targeted therapy, retinoid therapy or hormonal therapy) within 4 weeks prior to C1D1. 11. Major surgery within 4 weeks prior to C1D1 12. Active joint inflammation or history of inflammatory arthritis or other immune disorder involving joints 13. Active infection involving IV antibiotics within 2 weeks prior to C1D1 14. Known history of, or active hepatitis B virus (HBV), hepatitis C virus (HCV) or active tuberculosis 15. Known history of human immunodeficiency virus (HIV) type 1/2 or other immunodeficiency disease 16. Subject has received a live vaccine within 4 weeks prior to C1D1 17. Known hypersensitivity to any component of recombinant protein production by CHO cells 18. Exposure to an investigational product or investigational device in another clinical study within 4 weeks prior to C1D1, or is scheduled to participate in another clinical study involving an investigational product or device during the course of this study 19. Subject is nursing or intends to begin nursing during the course of the study 20. Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s) (eg, blood tests, ECG), that in medical judgment of the investigator may impede the subject's participation in the study, pose increased risk to the subject, and/or confound the results of the study 21. Subject is a family member or employee of the investigator

Additional Information

Official title A Phase 2a Randomized, Open-label Study to Assess the Safety, Tolerability, and Efficacy of BAX69 in Combination With 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Baxalta US Inc..
Location data was received from the National Cancer Institute and was last updated in August 2016.