NCT02235324

Brief Summary

This phase II trial studies how long it takes colorectal cancer resistant to standard treatment to grow while receiving treatment with ziv-aflibercept, and how well adding fluorouracil and leucovorin calcium to ziv-aflibercept works in treating patients with stage IV colorectal cancer after they progress on ziv-aflibercept alone. Ziv-aflibercept may stop the growth of colorectal cancer by blocking the formation of tumor blood vessels. Fluorouracil and leucovorin calcium are drugs used in chemotherapy. Fluorouracil works to stop the growth of tumors cells by preventing the cells from growing and dividing. Leucovorin calcium helps fluorouracil work better. Adding fluorouracil and leucovorin calcium to ziv-aflibercept may be an effective treatment for patients who progress on ziv-aflibercept alone.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Mar 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 4, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 9, 2014

Completed
6 months until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2017

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed
Last Updated

May 6, 2015

Status Verified

May 1, 2015

Enrollment Period

2 years

First QC Date

September 4, 2014

Last Update Submit

May 4, 2015

Conditions

Mucinous Adenocarcinoma of the ColonMucinous Adenocarcinoma of the RectumRecurrent Colon CancerRecurrent Rectal CancerSignet Ring Adenocarcinoma of the ColonSignet Ring Adenocarcinoma of the RectumStage IVA Colon CancerStage IVA Rectal CancerStage IVB Colon CancerStage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (2)

  • Progression-free survival during the first phase of the study

    Point and precision estimates, median and its 95% confidence interval (CI) will be provided. To examine associations between biomarkers and PFS1, the difference in progression-free survival by each biomarker level will be detected.

    Period from the start of ziv-aflibercept to the date of radiographic or clinical progression, death, or within 30 days off treatment

  • Progression-free survival during the second phase of the study

    Using the Simon's 2-stage optimum design, there is a 90% power to detect improvement of adding fluorouracil to ziv-aflibercept on PFS2 and the type I error rate is 2.3%. Point and precision estimates, median and its 95% CI will be provided.

    Period from the start of fluorouracil with ziv-aflibercept to the date of radiographic or clinical progression, death, or within 30 days off treatment

Secondary Outcomes (3)

  • Overall survival (OS)

    Period from treatment initiation with single agent ziv-aflibercept to death, assessed up to 3 years

  • Response rate assessed using Response Evaluation Criteria in Solid Tumors 1.1

    Up to 3 years

  • Incidence of adverse events graded according to NCI CTCAE version 4.0

    Within 30 days of the last administration of the study drug

Other Outcomes (2)

  • Plasma levels of PIGF

    Up to 3 years

  • mRNA level of VEGFR1, VEGFR2, and VEGF-A

    Up to 3 years

Study Arms (1)

Treatment (ziv-aflibercept, leucovorin calcium, fluorouracil)

EXPERIMENTAL

PHASE I: Patients receive ziv-aflibercept IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. At the time of progression, patients proceed to Phase II. PHASE II: Patients receive ziv-aflibercept IV over 1 hour, leucovorin calcium IV over 1 minute, and fluorouracil IV over 46 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: ziv-afliberceptDrug: leucovorin calciumDrug: fluorouracilOther: laboratory biomarker analysis

Interventions

ziv-afliberceptBIOLOGICAL

Given IV

Also known as: aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap
Treatment (ziv-aflibercept, leucovorin calcium, fluorouracil)
leucovorin calciumDRUG

Given IV

Also known as: CF, CFR, LV
Treatment (ziv-aflibercept, leucovorin calcium, fluorouracil)
fluorouracilDRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU
Treatment (ziv-aflibercept, leucovorin calcium, fluorouracil)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (ziv-aflibercept, leucovorin calcium, fluorouracil)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed stage IV colorectal adenocarcinoma previously treated with FOLFOX and FOLFIRI and bevacizumab, receipt of cetuximab or panitumumab is not required, and has shown progression or intolerant of both oxaliplatin and irinotecan-based regimens; baseline tumor assessments must be done within 28 days of starting treatment
  • Patients must have lesions that can be easily biopsied
  • Representative tumor tissue specimens (paraffin block preferred)
  • Signed informed consent prior to initiation of any study-specific procedure or treatment, including agreement to two biopsies during the study
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Able to comply with the protocol, including tissue and blood sampling
  • Leukocytes \>= 3,000 per mm\^3
  • Absolute neutrophil count \>= 1,000 per mm\^3
  • Platelet count \>= 75,000 per mm\^3
  • Hemoglobin \>= 9 g/dL (may be transfused to maintain or exceed this level)
  • Creatinine clearance according to the Cockcroft and Gault formula of \>= 50 mL/min
  • Urine for proteinuria should be \< 2 +; patients discovered to have \>= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours
  • Total bilirubin \< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase and alanine aminotransferase \< 2.5 x ULN
  • International normalized ratio =\< 1.5 and activated prothrombin time =\< 1.5 x ULN for patients not receiving anti-coagulation therapy
  • +8 more criteria

You may not qualify if:

  • Radiotherapy to any site for any reason within 14 days prior to treatment
  • Uncontrolled intercurrent illness including, but not limited to
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study
  • History of arterial thromboembolic events
  • History of abdominal fistula formation, gastrointestinal perforation, or abdominal abscess within six months
  • History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding
  • Patients must not be pregnant or nursing
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
  • Any hemorrhage or bleeding event \>= CTCAE grade 3 within 4 weeks prior to the start of study medication
  • Non-healing wound, ulcer, or bone fracture
  • Inadequately controlled hypertension (systolic blood pressure \[SBP\] \> 150 mmHg, diastolic blood pressure \[DBP\] \> 100 mg Hg)
  • Known positivity for human immunodeficiency virus (HIV)
  • Malignancies other than colorectal adenocarcinoma within 5 years prior to treatment, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
  • Clinically detectable (by physical exam) third-space fluid collections (e.g. ascites or pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry
  • Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

Location

MeSH Terms

Conditions

Colonic NeoplasmsRectal Neoplasms

Interventions

afliberceptLeucovorinFluorouracil

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

FormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and CoenzymesUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Afsaneh Barzi

    University of Southern California

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 4, 2014

First Posted

September 9, 2014

Study Start

March 1, 2015

Primary Completion

March 1, 2017

Study Completion

March 1, 2018

Last Updated

May 6, 2015

Record last verified: 2015-05

Locations

US(1)