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Colorectal CancerPhase 2NCT03099486

Regorafenib Plus 5-Fluorouracil/Leucovorin Beyond Progression in mCRC

A Phase 2 study testing Regorafenib, 5-FU and Leucovorin in people with Colorectal Cancer, run by Fox Chase Cancer Center at 1 site 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

This is a single arm open label pilot phase II trial of Regorafenib PO plus 5-FU/LV infusion in 15 mCRC patients who progressed on prior Regorafenib monotherapy as well as 5-FU containing chemotherapy combinations.The study will enroll mCRC patients with prior progression on standard multi-agent combination… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Regorafenib, 5-FU and Leucovorin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
6 Oct 2017to 2 Jun 2020
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

  • mCRC with prior progression on standard multi-agent combination chemotherapy and regorafenib as a standard approved monotherapy. Progression on prior regorafenib is required for inclusion in this clinical study. Prior regimens may include FOLFOX -/+ bevacizumab, FOLFIRI -/+ bevacizumab or -/+ cetuximab (if KRAS wild-type) or panitumumab (if KRAS wilt-type). Other prior regimens may include 5-FU or capecitabine -/+ bevacizumab, irinotecan -/+ cetuximab or panitumumab, FOLFIRI -/+ ziv-aflibercept or ramucirumab.
  • Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy. Patients who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated. Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed in the study.
  • Patients previously treated with chemotherapy must have at least 4 weeks period between the last dose of previous chemotherapy and the first dose in this clinical study. Patients previously treated with biologics such as Avastin, Zaltrap, Erbitux, and Vectibix must have at least 6 weeks period between the last dose of previous chemotherapy and the first dose in this clinical study.
  • Measurable metastatic disease that is refractory.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Patients are included regardless of KRAS/NRAS, BRAF, p53, or microsatellite instability (MSI) status
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  • Age ≥ 18 years.
  • Life expectancy of at least 8 weeks (2 months).
  • Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
  • Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
  • Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
  • Serum creatinine ≤ 1.5 x the ULN
  • International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x ULN.
  • Platelet count > 100000 /mm3, hemoglobin (Hb) > 9 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm3. Blood transfusion to meet the inclusion criteria will not be allowed.
  • Subject must be able to swallow and retain oral medication.
  • Up to 5 of the 15 patients will be allowed to have had other approved or investigational drugs after prior progression of Regorafenib monotherapy. (all patients enrolled in this trial must have had prior progression on regorafenib therapy). This may include TAS102, off-label therapy that may have been prescribed based on tumor genomic profiling or any investigational agents on a clinical trial.
  • No more than grade 2 toxicity with last previous cycle of regorafenib mono therapy.

Who cannot join

  • Patients receiving any concurrent investigational agents
  • Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
  • Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.
  • Active or clinically significant cardiac disease including:
  • Congestive heart failure - New York Heart Association (NYHA) > Class II.
  • Active coronary artery disease.
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  • Suspected Long QT syndrome defined as QTc interval > 500 milliseconds at baseline.
  • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
  • Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of study medication.
  • Subjects diagnosed with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 3 months of start of study treatment.
  • Patients with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated ductal carcinoma in situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive aerodigestive neoplasms, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed; all cancer treatments must be completed at least 3 years prior to registration.
  • Patients with phaeochromocytoma.
  • Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
  • Ongoing infection > Grade 2 NCI-CTCAE v4.0.
  • Symptomatic metastatic brain or meningeal tumors.
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture.
  • Major surgical procedure or significant traumatic injury within 28 days before start of study medication
  • Renal failure requiring hemo-or peritoneal dialysis.
  • Dehydration Grade ≥1 NCI-CTCAE v4.0.
  • Patients with seizure disorder requiring medication.
  • Persistent proteinuria ≥ Grade 3 per NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine protein: creatinine ratio on a random urine sample).
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
  • Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.0 Grade 2 dyspnea).
  • History of organ allograft (including corneal transplant).
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.
  • Any malabsorption condition.
  • Women who are pregnant or breast-feeding.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
  • Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids.
  • However, prophylactic anticoagulation as described below is allowed: i. Low dose warfarin (1 mg orally, once daily) with PT-INR ≤ 1.5 x ULN is permitted.
  • Low dose aspirin (≤ 100 mg daily). iii. Prophylactic doses of heparin. iv. Low molecular weight heparin Subjects who are prophylactically treated with an agent such as warfarin or heparin require close monitoring (day5 of cycle 1 and day 1 of each cycle) of their INR/PTT. If either of these values are above the therapeutic range, the doses should be modified and the assessments should be repeated weekly until they are stable.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: A Pilot Phase II, Single Arm, Open Label, Investigator-initiated Clinical Trial of Regorafenib Plus 5-Fluorouracil/Leucovorin (5FU/LV) Beyond Progression on Regorafenib Monotherapy in Metastatic Colorectal Cancer (mCRC)

This is a single arm open label pilot phase II trial of Regorafenib PO plus 5-FU/LV infusion in 15 mCRC patients who progressed on prior Regorafenib monotherapy as well as 5-FU containing chemotherapy combinations.The study will enroll mCRC patients with prior progression on standard multi-agent combination chemotherapy and progression on regorafenib monotherapy.

Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • RegorafenibDrug

    The dose of Regorafenib is 160 mg PO daily D1-D21 of 28-day cycle or last tolerated dose while on Regorafenib monotherapy.

  • 5-FUDrug

    5-FU dose D1 and D15 of 28 day cycle i400 mg/m2 bolus over 10 mins followed by 2400 mg/m2 continuous infusion over 46 hours

  • LeucovorinDrug

    D1 and D15 of 28 day cycle Leucovorin 400 mg/m2 over 2 hours,

Study groups in NCT03099486
Study groupRoleWhat they receive
Regorafenib + 5FU/LV Treatment ArmExperimentalNot described
Receives: Drug: Regorafenib; Drug: 5-FU; Drug: Leucovorin

What is being measured

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

  1. Progression Free Survival (PFS) at 2 Months

    PFS at 2 months in mCRC patients who progress on regorafenib monotherapy and are treated with regorafenib and 5-FU/LV combination therapy.

    Measured: 2 months

Secondary outcomes (3)

  1. Overall Survival Rate

    Overall survival will be calculated from the day of first treatment until death

    Measured: 1 years

  2. Best Overall Response

    This will be calculated from the day of first treatment dose until disease progression or death, whichever occurs earlier

    Measured: 1-2 years

  3. Number of Toxicities Due to Regorafenib and 5-FU/LV Combination Therapy

    Number of toxicities due to combination therapy will be summarized by frequencies and grades of toxicities due to the combination therapy according to CTCAE 4.03 criteria

    Measured: 1-2 years

Timeline

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

  1. First posted4 Apr 2017
  2. Study start6 Oct 2017
  3. Primary completion2 Jun 2020
  4. Study completion2 Jun 2020

Why it stopped: Administrative change

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03099486
Sponsor's protocol ID
17-1023
Other IDs
GI-094
Status last verified
Jan 2022
First submitted
23 Mar 2017
Last updated
7 Feb 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib, 5-FU and Leucovorin in people with Colorectal Cancer, run by Fox Chase Cancer Center at 1 site 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 19 inclusion and 34 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 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 7 Feb 2022). 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?

Progression Free Survival (PFS) at 2 Months (time frame: 2 months). 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 NCT03099486.

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 7 Feb 2022.

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