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

Phase 1
18 Years
Open (Enrolling)
Oxaliplatin Refractory/Intolerant KRAS Mutant Colorectal Cancer

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Trial Information

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

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, and there is no drug that can be
combined with it to improve clinical outcomes.

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 and FOLFIRI. FOLFIRI 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 12 to 20 patients.

Inclusion Criteria:

Each patient MUST:

- Have histologically confirmed cancer of the colon or rectum with radiologically
documented and measurable metastases (high CEA alone is insufficient for study

- Have received 3 or fewer regimens 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 resolved.

- 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 with liver metastases)

- Negative pregnancy test for females with childbearing potential.

- 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.

Exclusion Criteria: No patient may:

- Receive concurrent therapy with any other investigational anticancer agent while on

- Have received more than 3 chemotherapy regimens in the metastatic setting.

- Have brain metastases.

- Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or

- Have received chemotherapy, radiotherapy, immunotherapy or hormonal therapy or had
surgery (except biopsies) within 28 days prior to receiving the study drug.

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

During the first cycle of treatment (4 week cycle)

Safety Issue:



United States: Food and Drug Administration

Study ID:

REO 022



Start Date:

December 2010

Completion Date:

Related Keywords:

  • Oxaliplatin Refractory/Intolerant KRAS Mutant Colorectal Cancer
  • Colorectal
  • Cancer
  • Chemotherapy
  • Reovirus
  • Oncolytic virus
  • Fluorouracil
  • Irinotecan
  • Leucovorin
  • Colorectal Neoplasms



The Ohio State UniversityColumbus, Ohio  43210
Montefiore Medical Center/Albert Einstein College of MedicineBronx, New York  10461
New York Presbyterian Hospital/ Weill Cornell Medical CollegeNew York, New York  10065