Phase 2a Study of BAX69 and 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer

NCT ID: NCT02448810

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-15
• Study Completion Date: 2017-02-15

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).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Subjects with mutated tumor (mt) (KRAS or NRAS)

Subjects stratified according to their mutation status.

Group Type: EXPERIMENTAL

BAX69 + infusional 5-FU/LV

Intervention Type: BIOLOGICAL

Study Part 1: Safety Run-in

• Administered weekly as part of a 4 week treatment cycle
• Intravenous injection

Part 1: Subjects with wild-type (wt) tumor (KRAS and NRAS wt)

Subjects stratified according to their mutation status.

Group Type: EXPERIMENTAL

BAX69 + panitumumab

Intervention Type: BIOLOGICAL

Study Part 1: Safety Run-in

• Administered weekly as part of a 4 week treatment cycle
• Intravenous injection

Part 2: Subjects with KRAS or NRAS mutated

Subjects stratified according to their mutation status.

Group Type: EXPERIMENTAL

BAX69 + 5-FU/LV

Intervention Type: BIOLOGICAL

Study Part 2: Administered weekly as part of a 4 week treatment cycle

•Intravenous injection

Part 2: Subjects with KRAS and NRAS wt tumor

Subjects stratified according to their mutation status.

Group Type: EXPERIMENTAL

BAX69 + panitumumab

Intervention Type: BIOLOGICAL

Study Part 2: Administered weekly as part of a 4 week treatment cycle

•Intravenous injection

Part 2: Standard of Care- Subjects with KRAS or NRAS mutated

Subjects stratified according to their mutation status.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

• Investigator's choice
• Dose according to drug label

Part 2: Standard of Care- Subjects with KRAS and NRAS wt tumor

Subjects stratified according to their mutation status.Subjects stratified according to their mutation status.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: BIOLOGICAL

• Investigator's choice
• Dose according to drug label
• Choice includes panitumumab in KRAS &NRAS wt group only

Interventions

BAX69 + infusional 5-FU/LV

Study Part 1: Safety Run-in

• Administered weekly as part of a 4 week treatment cycle
• Intravenous injection

Intervention Type: BIOLOGICAL

BAX69 + panitumumab

Study Part 1: Safety Run-in

• Administered weekly as part of a 4 week treatment cycle
• Intravenous injection

Intervention Type: BIOLOGICAL

BAX69 + 5-FU/LV

Study Part 2: Administered weekly as part of a 4 week treatment cycle

•Intravenous injection

Intervention Type: BIOLOGICAL

BAX69 + panitumumab

Study Part 2: Administered weekly as part of a 4 week treatment cycle

•Intravenous injection

Intervention Type: BIOLOGICAL

Standard of Care

• Investigator's choice
• Dose according to drug label

Intervention Type: DRUG

Standard of Care

• Investigator's choice
• Dose according to drug label
• Choice includes panitumumab in KRAS &NRAS wt group only

Intervention Type: BIOLOGICAL

Other Intervention Names

Macrophage Migration Inhibitory Factor Antibody (Anti-MIF); Imalumab; Imalumab; Anti-MIF; Imalumab; Anti-MIF; Imalumab; Anti-MIF

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, United States

Indiana University Health

Goshen, Indiana, United States

Maryland Oncology Hematology, P.A.

Rockville, Maryland, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mount Sinai Beth Israel

New York, New York, United States

Montefiore Einstein Center for Cancer Care

The Bronx, New York, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

The Jones Clinic, PC

Germantown, Tennessee, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

CTRC at University of Texas Health Science Center

San Antonio, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000896-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

391401

Identifier Type: -

Identifier Source: org_study_id