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Metastatic Colorectal CancerPhase 2NCT02448810

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

A Phase 2 study testing BAX69 + infusional 5-FU/LV, BAX69 + panitumumab and BAX69 + 5-FU/LV in people with Metastatic Colorectal Cancer, run by Baxalta now part of Shire at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
BAX69 + infusional 5-FU/LV, BAX69 + panitumumab and BAX69 + 5-FU/LV
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
12 sitesUnited States
Study dates
15 Jun 2015to 15 Feb 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Adequate renal function, defined as serum creatinine ≤ 2.0 times ULN and creatinine clearance > 50 mL/min
  • Adequate liver function, defined as:
  • 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
  • Bilirubin ≤ 2.0 times ULN, unless subject has known Gilbert's syndrome
  • Adequate venous access
  • 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
  • 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
  • Subject is willing and able to comply with the requirements of the protocol.

Who cannot join

  • 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)
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  • 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
  • Subject has received a live vaccine within 4 weeks prior to C1D1
  • Known hypersensitivity to any component of recombinant protein production by CHO cells
  • 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
  • Subject is nursing or intends to begin nursing during the course of the study
  • 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
  • Subject is a family member or employee of the investigator

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina, 29412

  • Mary Crowley Cancer Research Center

    Dallas, Texas, 75230

  • The Jones Clinic, PC

    Germantown, Tennessee, 38138

  • Indiana University Health

    Goshen, Indiana, 46526

  • Joliet Oncology-Hematology Associates, Ltd.

    Joliet, Illinois, 60435

  • Mount Sinai Beth Israel

    New York, New York, 10003

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Hematology Oncology Associates of the Treasure Coast

    Port Saint Lucie, Florida, 34952

  • Maryland Oncology Hematology, P.A.

    Rockville, Maryland, 20850

  • CTRC at University of Texas Health Science Center

    San Antonio, Texas, 78229

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Montefiore Einstein Center for Cancer Care

    The Bronx, New York, 10461

Other trials in United States

About this study

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

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).

Being tested
BAX69 + infusional 5-FU/LV, BAX69 + panitumumab, BAX69 + 5-FU/LV, Standard of Care
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAX69 + infusional 5-FU/LVBiological

    Also called Macrophage Migration Inhibitory Factor Antibody (Anti-MIF), Imalumab

    Study Part 1: Safety Run-in

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

  • BAX69 + panitumumabBiological

    Also called Imalumab, Anti-MIF

    Study Part 1: Safety Run-in

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

  • BAX69 + 5-FU/LVBiological

    Also called Imalumab, Anti-MIF

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

    •Intravenous injection

  • BAX69 + panitumumabBiological

    Also called Imalumab, Anti-MIF

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

    •Intravenous injection

  • Standard of CareDrug

    • Investigator's choice
    • Dose according to drug label

  • Standard of CareBiological

    • Investigator's choice
    • Dose according to drug label
    • Choice includes panitumumab in KRAS \&NRAS wt group only
Study groups in NCT02448810
Study groupRoleWhat they receive
Part 1: Subjects with mutated tumor (mt) (KRAS or NRAS)ExperimentalSubjects stratified according to their mutation status.
Receives: Biological: BAX69 + infusional 5-FU/LV
Part 1: Subjects with wild-type (wt) tumor (KRAS and NRAS wt)ExperimentalSubjects stratified according to their mutation status.
Receives: Biological: BAX69 + panitumumab
Part 2: Subjects with KRAS or NRAS mutatedExperimentalSubjects stratified according to their mutation status.
Receives: Biological: BAX69 + 5-FU/LV
Part 2: Subjects with KRAS and NRAS wt tumorExperimentalSubjects stratified according to their mutation status.
Receives: Biological: BAX69 + panitumumab
Part 2: Standard of Care- Subjects with KRAS or NRAS mutatedActive comparatorSubjects stratified according to their mutation status.
Receives: Drug: Standard of Care
Part 2: Standard of Care- Subjects with KRAS and NRAS wt tumorActive comparatorSubjects stratified according to their mutation status.Subjects stratified according to their mutation status.
Receives: Biological: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: From start of study treatment up to 28 days

Secondary outcomes (6)

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

    Number of participants with occurrence of binding and/or neutralizing anti-imalumab antibodies were reported.

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

  2. Number of Participants With Incidence of Infusion Reactions After Imalumab Administration

    Infusion reaction was defined as any relevant sign or symptom occurring during or after imalumab infusion and considered by the investigator as an infusion reaction.

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

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

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any AE that results in any of the following outcomes: death, a life-threatening event, inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, other medically important events based upon appropriate medical judgement. TEAEs was defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments.

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

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

    Number of participants with response evaluation according to RECIST v1.1 was evaluated according to complete response (CR): disappearance of all target and non-target lesions and no new lesions; partial response (PR): >= 30 percent (%) decrease in the sum of diameters of target lesions (compared to baseline) and no new lesions; stable disease (SD): neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; progressive disease (PD): >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5 millimeter (mm) (compared to the previous minimum sum) or progression of a new lesion.

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

  5. Overall Survival

    Overall survival was defined as the time from randomization until death due to any cause. Here, number of participants analyzed was based on the number of participants who underwent death.

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

  6. 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)

    EORTC QLQ-C30 was a validated instrument used to measure QoL and assess symptoms and side effects of treatment and the impact on everyday life.The QLQ-C30 was composed of: A) 5 multi-item functioning scales(physical, role, social, emotional and cognitive), that were answered on a 4-point scale (1=Not at all,2=A Little,3=Quite a Bit,4=Very Much). Each score range from 0 to 100 with a higher score representing a higher level of functioning and a better QoL. B) A global health status/QoL scale that was answered on a 7-point scale (1=Very Poor to 7=Excellent). Each score range from 0 to 100 with a higher score representing a better QoL. C) 9 symptom scales(fatigue, nausea/vomiting,pain,financial impact/difficulties,appetite loss,diarrhea, constipation,sleep disturbance/insomnia and dyspnea), that were answered on a 4-point scale (1=Not at all,2=A Little,3=Quite a Bit,4=Very Much). Each score range from 0 to 100 with a higher score representing a greater degree of symptoms and a worse QoL.

    Measured: Baseline, 21 Months (EOT) up to follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2015 (estimated)
  2. Study start15 Jun 2015
  3. Primary completion15 Feb 2017
  4. Study completion15 Feb 2017

Why it stopped: Based on overall benefit-risk assessment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
115 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02448810
Sponsor's protocol ID
391401
Other IDs
2015-000896-28, 2015
Status last verified
May 2021
First submitted
15 May 2015
Last updated
25 May 2021
Data monitoring committee
Yes
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BAX69 + infusional 5-FU/LV, BAX69 + panitumumab and BAX69 + 5-FU/LV in people with Metastatic Colorectal Cancer, run by Baxalta now part of Shire at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 2: Progression-Free Survival (PFS) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02448810.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.

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