Clinical trial NCT02448810: Phase 2a Study of BAX69 and 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-05-20
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Part 2: Progression-Free Survival (PFS)
timeFrame: From start of the study up to safety follow-up visit occurred (30 [-/+7]) days after the last dose of study treatment or until disease progression
measure: Part 1: Number of Participants With Occurrence of Dose Limiting Toxicity (DLT)
timeFrame: From start of study treatment up to 28 days
Secondary outcomes:
measure: Number of Participants With Occurrence of Binding and/or Neutralizing Anti-imalumab Antibodies
timeFrame: From start of study drug administration up to end of treatment (EOT) (approximately 21 Months)
measure: Number of Participants With Incidence of Infusion Reactions After Imalumab Administration
timeFrame: From start of study drug administration up to EOT (approximately 21 Months)
measure: Number of Participants With Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to EOT (approximately 21 Months)
measure: Number of Participants With Response Evaluation According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Day 28 of Cycle 2 followed by every 2 Cycles of 28 day Cycles: Day 56, Day 112, Day 168 and Day 224
measure: Overall Survival
timeFrame: From start of study drug administration up to EOT (approximately 21 Months)
measure: Change From Baseline for Quality of Life (QoL) Measure - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Baseline, 21 Months (EOT) up to follow-up
Other outcomes:
Locations:
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Ltd.
state: Illinois
city: Goshen
country: United States
facility: Indiana University Health
state: Indiana
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Einstein Center for Cancer Care
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Germantown
country: United States
facility: The Jones Clinic, PC
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: San Antonio
country: United States
facility: CTRC at University of Texas Health Science Center
state: Texas
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: