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

NCT02448810 | Terminated Phase 2 Results DMC

• 2 other identifiers: 3914012015-000896-28
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 12

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

Outcome Measures

Primary Outcomes (2)

• Part 2: Progression-Free Survival (PFS)

  PFS was defined as time between treatment initiation and tumor progression (per Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1 criteria) or death from any cause, with censoring of participants who were lost to follow-up or withdrew consent.

  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

• Part 1: Number of Participants With Occurrence of Dose Limiting Toxicity (DLT)

  DLT was defined as any drug-related treatment-emergent adverse event (TEAE) (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v4.03) that occurs during the first 28 days after treatment start and that meets any of the following criteria: i) Any \>= Grade 3 non-hematologic toxicity (excluding: mucositis/stomatitis of Grade 3; diarrhea of \<3 days duration; nausea and vomiting \<3 days duration; fatigue of \<7 days duration; alopecia; single laboratory value out of the normal range that has no clinical significance and that resolves to \<= Grade 2 with adequate measures within 7 days) ii) Any Grade 4 hematologic toxicity (excluding: grade 4 neutropenia lasting for \<= 5 days; isolated grade 4 lymphocytopenia) iii) Grade 3 febrile neutropenia iv) Grade 3 thrombocytopenia associated with bleeding v) Any life-threatening complication or abnormality not covered in NCI CTCAEv4.03.

  From start of study treatment up to 28 days

Secondary Outcomes (6)

• Number of Participants With Occurrence of Binding and/or Neutralizing Anti-imalumab Antibodies

  From start of study drug administration up to end of treatment (EOT) (approximately 21 Months)

• Number of Participants With Incidence of Infusion Reactions After Imalumab Administration

  From start of study drug administration up to EOT (approximately 21 Months)

• Number of Participants With Serious Adverse Events (SAEs) and Treatment-emergent Adverse Events (TEAEs)

  From start of study drug administration up to EOT (approximately 21 Months)

• Number of Participants With Response Evaluation According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Day 28 of Cycle 2 followed by every 2 Cycles of 28 day Cycles: Day 56, Day 112, Day 168 and Day 224

• Overall Survival

  From start of study drug administration up to EOT (approximately 21 Months)

Study Arms (6)

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

EXPERIMENTAL

Subjects stratified according to their mutation status.

Biological: BAX69 + infusional 5-FU/LV

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

EXPERIMENTAL

Subjects stratified according to their mutation status.

Biological: BAX69 + panitumumab

Part 2: Subjects with KRAS or NRAS mutated

EXPERIMENTAL

Subjects stratified according to their mutation status.

Biological: BAX69 + 5-FU/LV

Part 2: Subjects with KRAS and NRAS wt tumor

EXPERIMENTAL

Subjects stratified according to their mutation status.

Biological: BAX69 + panitumumab

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

ACTIVE COMPARATOR

Subjects stratified according to their mutation status.

Drug: Standard of Care

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

ACTIVE COMPARATOR

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

Biological: Standard of Care

Interventions

BAX69 + infusional 5-FU/LV BIOLOGICAL

Study Part 1: Safety Run-in * Administered weekly as part of a 4 week treatment cycle * Intravenous injection

Also known as: Macrophage Migration Inhibitory Factor Antibody (Anti-MIF), Imalumab

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

BAX69 + panitumumab BIOLOGICAL

Study Part 1: Safety Run-in * Administered weekly as part of a 4 week treatment cycle * Intravenous injection

Also known as: Imalumab, Anti-MIF

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

BAX69 + 5-FU/LV BIOLOGICAL

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

Also known as: Imalumab, Anti-MIF

Part 2: Subjects with KRAS or NRAS mutated

Standard of Care DRUG

* Investigator's choice * Dose according to drug label

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of a signed informed consent
• Male and female subjects 18 years of age and older at the time of screening
• Subjects who progressed after receiving at least 2, but no more than 3, prior SoC treatment lines
• Anticipated life expectancy \>3 months at the time of screening
• Weight between 40 kg and 180 kg
• Histologically or cytologically confirmed diagnosis of CRC
• Metastatic CRC not amenable to surgical resection
• 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)
• At least 1 measurable lesion as defined by RECIST v1.1
• ECOG PS of 0-2
• Adequate hematological function, defined as:
• Platelet count ≥ 100,000/μL
• Prothrombin time and activated partial thromboplastin time (aPTT) \< 1.5 times the upper limit of normal (ULN)
• Absolute neutrophil count (ANC) ≥ 1,000/μL
• Hemoglobin ≥ 9 g/dL, without the need for transfusion in the 2 weeks prior to screening

You may not qualify if:

• Known central nervous system metastases
• 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
• Prior treatment with panitumumab for subjects with KRAS and NRAS wt tumor
• Residual AE from previous treatment \> Grade 1
• Prior intolerance to fluoropyrimidine for subjects with KRAS or NRAS mut tumor
• 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)
• Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg confirmed upon repeated measures
• LVEF \< 40% as determined by echocardiogram performed at screening or within 90 days prior to C1D1
• QT/QTc interval \> 450 msec, as determined by screening ECG performed no earlier than 1 week before C1D1
• Prior anti-tumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular targeted therapy, retinoid therapy or hormonal therapy) within 4 weeks prior to C1D1.
• Major surgery within 4 weeks prior to C1D1
• Active joint inflammation or history of inflammatory arthritis or other immune disorder involving joints
• Active infection involving IV antibiotics within 2 weeks prior to C1D1
• Known history of, or active hepatitis B virus (HBV), hepatitis C virus (HCV) or active tuberculosis
• Known history of human immunodeficiency virus (HIV) type 1/2 or other immunodeficiency disease

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (12)

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, 60435, United States

Location

Indiana University Health

Goshen, Indiana, 46526, United States

Location

Maryland Oncology Hematology, P.A.

Rockville, Maryland, 20850, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Montefiore Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29412, United States

Location

The Jones Clinic, PC

Germantown, Tennessee, 38138, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

CTRC at University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Standard of Care

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

On 2016 DEC 16, the data safety monitoring board (DSMB) reviewed the periodic safety data, and in addition also reviewed available efficacy data from the first 33 PFS events and non-clinical information and recommended to terminate Study 391401.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2015
• First Posted: May 20, 2015
• Study Start: June 15, 2015
• Primary Completion: February 15, 2017
• Study Completion: February 15, 2017
• Last Updated: May 25, 2021
• Results First Posted: March 19, 2018

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (12)