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KRAS Mutant Metastatic Colorectal CancerPhase 1NCT01274624

Study of REOLYSIN® in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer

A Phase 1 study testing REOLYSIN®, Irinotecan and Leucovorin in people with KRAS Mutant Metastatic Colorectal Cancer, run by Oncolytics Biotech at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1 dose-escalation study with three dose levels to determine the maximum tolerated dose of REOLYSIN® combined with FOLFIRI and bevacizumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
KRAS Mutant Metastatic Colorectal Cancer
What is being tested?
REOLYSIN®, Irinotecan and Leucovorin
Type of treatment
Injection or infusion
How many people
36 participants
Where
2 sitesUnited States
Study dates
Dec 2010to Nov 2018
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Have histologically confirmed cancer of the colon or rectum with radiologically documented and measurable metastases (high CEA alone is insufficient for study entry).
  • Have received an oxaliplatin-based chemotherapy regimen in the metastatic setting or relapsed within 6 months of completion of adjuvant therapy containing oxaliplatin.
  • Not have received prior FOLFIRI or irinotecan in the metastatic setting.
  • Have his/her tumor assessed for KRAS status and found to be mutation positive.
  • Have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have been resolved.
  • Be at least 18 years of age.
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  • Have an ECOG Performance Score of ≤ 2.
  • Have a life expectancy of at least 3 months.
  • Have baseline laboratory results as follows:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9 [SI unit 10^9/L]
  • Platelets ≥ 100 x10^9 [SI units 10^9/L] (without platelet transfusion)
  • Hemoglobin ≥ 9.0 g/dL [SI units gm/L] (with or without RBC transfusion)
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Bilirubin ≤ ULN
  • AST/ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
  • Negative pregnancy test for females with childbearing potential.
  • Proteinuria < grade 2.
  • Have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
  • Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.
  • Be medically eligible to receive bevacizumab

Who cannot join

  • Receive concurrent therapy with any other investigational anticancer agent while on study.
  • Have previously received irinotecan or FOLFIRI in the metastatic setting (patient is eligible if he/she had received irinotecan or FOLFIRI as adjuvant therapy more than 6 months before entry into the study)
  • Have brain metastases.
  • Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
  • Have received >20 Gy of radiation to the pelvis.
  • Have received chemotherapy, immunotherapy, hormonal therapy or had major surgery within 28 days; or received radiotherapy within 14 days; or minor surgery within 7 days prior to receiving the study drug.
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  • Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, be surgically sterile, or be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
  • Have clinically significant cardiac disease (New York Heart Association, Class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction within 1 year prior to study entry, or Grade 2 or higher compromised left ventricular ejection fraction.
  • Have dementia or altered mental status that would prohibit informed consent.
  • Have any other acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.
  • Have uncontrolled hypertension, proteinuria, or recent major surgery (all clinical parameters related to bevacizumab use). Any other clinical parameter considered important should be discussed with the medical monitor.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • New York Presbyterian Hospital/ Weill Cornell Medical College

    New York, New York, 10065

  • Montefiore Medical Center/Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: A Multicenter Phase 1 Study of Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination With Irinotecan/Fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer

This is a Phase 1 dose-escalation study with three dose levels to determine the maximum tolerated dose of REOLYSIN® combined with FOLFIRI and bevacizumab.

Read the detailed description

Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. Reovirus has been shown to replicate selectively in Ras-transformed cells causing cell lysis. Activating mutations in ras or mutation in oncogenes signaling through the ras pathway may occur in as many as 80% of human tumors. The specificity of the reovirus for Ras-transformed cells, coupled with its relatively nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate. Eligible patients for this study include those with histologically confirmed cancer of the colon or rectum with Kras mutation and measurable disease.

Cetuximab and panitumumab have shown to be ineffective in patients whose tumors have a KRAS mutation. Therefore, currently, for patients with a KRAS mutation, the only option after failure of front-line therapy is irinotecan or FOLFIRI. Over the past year, two randomized phase III trials have demonstrated that OS and PFS for these patients increase when bevacizumab is combined with the standard FOLFIRI therapy.

The trial is a Phase I dose escalation study with four dose levels, comprising cohorts of three to six patients, to determine a maximum tolerated dose and dose-limiting toxicities with the combination of REOLYSIN®, bevacizumab, and FOLFIRI. FOLFIRI and bevacizumab will be administered on the first day of a two week (14-day) cycle, while REOLYSIN® will be administered on days one through five of a four week (28-day) cycle.

The study is expected to enroll 20 to 32 patients.

Being tested
REOLYSIN®, Irinotecan, Leucovorin, Fluorouracil (5-FU), Bevacizumab
Keywords
Colorectal, Cancer, REOLYSIN®, Chemotherapy, FOLFIRI, Reovirus, Oncolytic virus, Fluorouracil, Irinotecan, Leucovorin, Bevacizumab
Medical subject headings
Neoplasms

What participants receive

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

  • REOLYSIN®Biological

    Also called Reovirus serotype 3 Dearing Strain

    1 hour intravenous infusion administered on Days 1, 2, 3, 4, and 5 every 4 weeks.

  • IrinotecanDrug

    90-minute intravenous infusion on Day 1 every 2 weeks. Dose levels of 125 mg/m2, 150 mg/m2, 150 mg/m2, 180 mg/m2.

  • LeucovorinDrug

    2-hour infusion of 400 mg/m2 on Day 1 every 2 weeks.

  • Fluorouracil (5-FU)Drug

    400 mg/m2 intravenous bolus followed by 2400 mg/m2 as a continuous intravenous infusion over 46 hours administered on Day 1 every 2 weeks.

  • BevacizumabDrug

    30, 60 or 90 minute infusion on Day 1 every 2 weeks. Dose level 5 mg/kg.

What is being measured

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

  1. Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose

    Measured: During the first cycle of treatment (4 week cycle)

  2. Pharmacokinetic parameters for irinotecan and 5-FU when combined with REOLYSIN®

    Measured: During the first cycle of treatment (4 week cycle)

Secondary outcomes (4)

  1. CEA and Objective Response, Clinical Benefit Rate (PR, CR, SD), progression-free survival, and overall survival (PFS and OS)

    Measured: Assessed every 8 weeks until disease progression or death

  2. Safety and tolerability of REOLYSIN® when administered in combination with FOLFIRI and bevacizumab

    Measured: During study and within 30 days of the last dose of REOLYSIN

  3. Correlative studies including determination of specific genetic mutations and aberrant signalling pathways from tumor tissue to identify novel biomarkers of response and efficacy

    Measured: During and within 30 days of the last dose of REOLYSIN®

  4. In vitro studies in human-derived colorectal cancer cells including the isogenic cell lines, to study the mechanism and scientific basis of synergy between irinotecan and reovirus

    Measured: During study and within 30 days of the last dose of REOLYSIN®

Timeline

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

  1. First posted11 Jan 2011 (estimated)
  2. Study startDec 2010
  3. Primary completionFeb 2018
  4. Study completionNov 2018

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01274624
Sponsor's protocol ID
REO 022
Status last verified
Dec 2018
First submitted
7 Jan 2011
Last updated
19 Dec 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing REOLYSIN®, Irinotecan and Leucovorin in people with KRAS Mutant Metastatic Colorectal Cancer, run by Oncolytics Biotech at 2 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 20 inclusion and 11 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: finished, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose (time frame: During the first cycle of treatment (4 week cycle)). 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 NCT01274624.

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 19 Dec 2018.

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