Carcinoma, Non-small Cell LungPhase 2NCT00861627
Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin for Non-Small Cell Lung Cancer With KRAS or EGFR Activation
A Phase 2 study testing REOLYSIN®, Carboplatin and Paclitaxel in people with Carcinoma, Non-small Cell Lung, run by Oncolytics Biotech at 2 sites in United States.
Trial summary
The purpose of this Phase 2 study is to investigate whether intravenous administration of a wild type reovirus (REOLYSIN®) in combination with paclitaxel and carboplatin is effective and safe in the treatment of Non-Small Cell Lung Cancer with KRAS or EGFR activation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-small Cell Lung
- What is being tested?
- REOLYSIN®, Carboplatin and Paclitaxel
- Type of treatment
- Injection or infusion
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2009to Nov 2015
- Phase
- Phase 2
- 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 or cytologically confirmed stage IIIB (pleural effusion; IVA on revised IASLC staging) or stage IV, or recurrent, non-small cell lung cancer with evidence of RAS- or EGFR- activation in their tumors, as defined by EGFR activating mutations in exons 18 to 21, EGFR FISH amplification, or K-ras mutations in exon 2 (codons 12,13,61).
- have evidence of measurable disease. For patients previously irradiated, the measurable lesion(s) must be outside of the treated field.
- be chemotherapy naïve for their metastatic or recurrent NSCLC. Prior adjuvant chemotherapy or chemo-XRT for treatment of localized disease is allowed, provided it has been ≥ 6 months since the last chemotherapy infusion. Previous radiation for palliative purposes is also allowed, as long as it has been ≥4 weeks from the last dose.
- Patients who have been previously treated with EGFR tyrosine kinase inhibitors as their only systemic treatment are eligible, provided this treatment has been discontinued for ≥4 weeks. Patients who have received erlotinib as first line treatment without chemotherapy and experience tumor progression will be eligible.
- have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) Grade ≤ 1. Surgery (except biopsies) must have occurred at least 28 days prior to study enrollment.
- have an ECOG Performance Score of ≤ 2.
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- have a life expectancy of at least 3 months.
- have baseline laboratory results as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10E9 [SI units 10^9/L]
- Platelets ≥ 100 x10E9 [SI units 10E9/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 ≤ 1.5 x ULN
- AST/ALT ≤ 2.5 x ULN
- Negative pregnancy test for females of childbearing potential.
- be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.
Who cannot join
- Receive concurrent therapy with any other anticancer agent while on study.
- Received chemotherapy within 6 months, or radiotherapy or EGFR therapy within 4 weeks, prior to entering the study or have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Have brain metastases. Patients with resected oligometastasis are eligible if post resection MRI demonstrates resolution. Gamma knife treated patients are also eligible, if there are no more than two treated metastases confined to the same area of the brain and a post treatment MRI shows a decrease in the metastases.
- Have ≥ grade 2 peripheral neuropathy at baseline.
- Have uncontrolled cardiac dysfunction, including a myocardial infarction in the preceding 6 months, or known cardiac ejection fraction < 40%.
- Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
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- Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
- Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements.
- Have dementia or altered mental status that would prohibit informed consent.
- Have any other severe, 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Ohio State University Medical Center, James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
Official title: Phase 2 Study of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Have KRAS or EGFR Activated Tumors
The purpose of this Phase 2 study is to investigate whether intravenous administration of a wild type reovirus (REOLYSIN®) in combination with paclitaxel and carboplatin is effective and safe in the treatment of Non-Small Cell Lung Cancer with KRAS or EGFR activation.
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.
Given the ability of reovirus to replicate and cause oncolysis in Ras-activated cells, the high incidence of K-ras mutations in lung cancers, and the Ras-mediated activation often encountered in EGFR-addicted tumors, the administration of REOLYSIN® in combination with chemotherapy is expected to result in enhanced clinical benefit in non-small cell lung cancer (NSCLC) patients with K-ras mutations and/or EGFR aberrant activation in their tumors. Patients with de novo or acquired EGFR mutations in their tumors that confer resistance to EGFR TKIs (e.g. T790) are expected to benefit as well. This is a single arm, open-label, Phase 2 study of REOLYSIN® given intravenously with paclitaxel and carboplatin every 3 weeks (21 days is defined as a cycle) in NSCLC patients with tumors driven by these pathways.
Paclitaxel at a dose of 175 mg/m2 will be given i.v. as a 3 hour infusion on Day 1 followed by carboplatin given i.v. AUC 5 mg/mL•minute. REOLYSIN® will be given over 60 min on Day 1 (starting after completion of the carboplatin infusion), and on Days 2 - 5. The treatment cycle will be repeated every 21 days.
Patients will receive 4 to 6 cycles of paclitaxel and carboplatin, at the treating physician's discretion according to standard of practice, in conjunction with REOLYSIN®. After completion of the 4 to 6 cycles of paclitaxel and carboplatin, REOLYSIN® may be continued as monotherapy Days 1-5 of each 21 day cycle until there is evidence of disease progression or unacceptable toxicity. Patients may continue to receive therapy under this protocol, provided they have not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction.
- Conditions
- Carcinoma, Non-small Cell Lung
- Being tested
- REOLYSIN®, Carboplatin, Paclitaxel
- Keywords
- REOLYSIN, reovirus, non-small cell lung cancer, carcinoma, oncolytics virus, chemotherapy, paclitaxel, carboplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma
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
3x10E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle
CarboplatinDrug
5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle
PaclitaxelDrug
175 mg/m2, 3 hour intravenous infusion, given on Day 1 of 21 day cycle
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the objective response rate (complete response (CR) + partial response (PR)) of the treatment regimen in the study population
Measured: For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met.
Secondary outcomes (4)
Determine the median duration of progression-free survival of patients receiving the study treatment.
Measured: during and following study
Determine the median to 1-year survival of patients receiving the study treatment.
Measured: up to one year
Evaluate the safety and tolerability of REOLYSIN® in combination with paclitaxel and carboplatin in this patient population.
Measured: within 30 days of last dose of REOLYSIN®
Determine the proportion of patients receiving the above treatment who are alive and free of disease progression at 6 months
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionSep 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-small Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncolytics Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Miguel Villalona, MD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00861627
- Sponsor's protocol ID
- REO 016
- Status last verified
- Dec 2015
- First submitted
- 12 Mar 2009
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Have KRAS or EGFR Activated Tumors
- ClinicalTrials.gov ID
- NCT00861627
- Acronym / sponsor ID
- REO 016
- Conditions
- Carcinoma, Non-small Cell Lung
- Keywords
- REOLYSIN, reovirus, non-small cell lung cancer, carcinoma, oncolytics virus, chemotherapy, paclitaxel, carboplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Oncolytics BiotechIndustry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Sep 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 13 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase 2 study is to investigate whether intravenous administration of a wild type reovirus (REOLYSIN®) in combination with paclitaxel and carboplatin is effective and safe in the treatment of Non-Small Cell Lung Cancer with KRAS or EGFR activation.
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.
Given the ability of reovirus to replicate and cause oncolysis in Ras-activated cells, the high incidence of K-ras mutations in lung cancers, and the Ras-mediated activation often encountered in EGFR-addicted tumors, the administration of REOLYSIN® in combination with chemotherapy is expected to result in enhanced clinical benefit in non-small cell lung cancer (NSCLC) patients with K-ras mutations and/or EGFR aberrant activation in their tumors. Patients with de novo or acquired EGFR mutations in their tumors that confer resistance to EGFR TKIs (e.g. T790) are expected to benefit as well. This is a single arm, open-label, Phase 2 study of REOLYSIN® given intravenously with paclitaxel and carboplatin every 3 weeks (21 days is defined as a cycle) in NSCLC patients with tumors driven by these pathways.
Paclitaxel at a dose of 175 mg/m2 will be given i.v. as a 3 hour infusion on Day 1 followed by carboplatin given i.v. AUC 5 mg/mL•minute. REOLYSIN® will be given over 60 min on Day 1 (starting after completion of the carboplatin infusion), and on Days 2 - 5. The treatment cycle will be repeated every 21 days.
Patients will receive 4 to 6 cycles of paclitaxel and carboplatin, at the treating physician's discretion according to standard of practice, in conjunction with REOLYSIN®. After completion of the 4 to 6 cycles of paclitaxel and carboplatin, REOLYSIN® may be continued as monotherapy Days 1-5 of each 21 day cycle until there is evidence of disease progression or unacceptable toxicity. Patients may continue to receive therapy under this protocol, provided they have not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- have histologically or cytologically confirmed stage IIIB (pleural effusion; IVA on revised IASLC staging) or stage IV, or recurrent, non-small cell lung cancer with evidence of RAS- or EGFR- activation in their tumors, as defined by EGFR activating mutations in exons 18 to 21, EGFR FISH amplification, or K-ras mutations in exon 2 (codons 12,13,61).
- have evidence of measurable disease. For patients previously irradiated, the measurable lesion(s) must be outside of the treated field.
- be chemotherapy naïve for their metastatic or recurrent NSCLC. Prior adjuvant chemotherapy or chemo-XRT for treatment of localized disease is allowed, provided it has been ≥ 6 months since the last chemotherapy infusion. Previous radiation for palliative purposes is also allowed, as long as it has been ≥4 weeks from the last dose.
- Patients who have been previously treated with EGFR tyrosine kinase inhibitors as their only systemic treatment are eligible, provided this treatment has been discontinued for ≥4 weeks. Patients who have received erlotinib as first line treatment without chemotherapy and experience tumor progression will be eligible.
- have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) Grade ≤ 1. Surgery (except biopsies) must have occurred at least 28 days prior to study enrollment.
Key exclusion criteria (10 listed)
- Receive concurrent therapy with any other anticancer agent while on study.
- Received chemotherapy within 6 months, or radiotherapy or EGFR therapy within 4 weeks, prior to entering the study or have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Have brain metastases. Patients with resected oligometastasis are eligible if post resection MRI demonstrates resolution. Gamma knife treated patients are also eligible, if there are no more than two treated metastases confined to the same area of the brain and a post treatment MRI shows a decrease in the metastases.
- Have ≥ grade 2 peripheral neuropathy at baseline.
- Have uncontrolled cardiac dysfunction, including a myocardial infarction in the preceding 6 months, or known cardiac ejection fraction < 40%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REOLYSIN®Also: reovirus serotype 3 Dearing Strain3x10E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle | Biological | – |
| Carboplatin5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle | Drug | – |
| Paclitaxel175 mg/m2, 3 hour intravenous infusion, given on Day 1 of 21 day cycle | Drug | – |
Primary outcome
Determine the objective response rate (complete response (CR) + partial response (PR)) of the treatment regimen in the study population
Time frame: For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met.
4 secondary outcomes
Determine the median duration of progression-free survival of patients receiving the study treatment.
Time frame: during and following study
Determine the median to 1-year survival of patients receiving the study treatment.
Time frame: up to one year
Evaluate the safety and tolerability of REOLYSIN® in combination with paclitaxel and carboplatin in this patient population.
Time frame: within 30 days of last dose of REOLYSIN®
Determine the proportion of patients receiving the above treatment who are alive and free of disease progression at 6 months
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miguel Villalona, MD principal investigator
Ohio State University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing REOLYSIN®, Carboplatin and Paclitaxel in people with Carcinoma, Non-small Cell Lung, 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 16 inclusion and 10 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 2 Dec 2015. 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 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?
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?
Determine the objective response rate (complete response (CR) + partial response (PR)) of the treatment regimen in the study population (time frame: For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2015.