Unspecified Childhood Solid Tumor, Protocol SpecificPhase 1NCT01240538
Viral Therapy in Treating Young Patients With Relapsed or Refractory Solid Tumors
A Phase 1 study testing wild-type reovirus, cyclophosphamide and laboratory biomarker analysis in people with Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 27 sites in 2 countries.
Trial summary
This phase I trial studies the side effects and the best dose of viral therapy in treating young patients with solid tumors that have come back or that have not responded to standard therapy. Some tumors have cells with a genetic weakness that makes them unable to fight off a virus called wild-type reovirus. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Unspecified Childhood Solid Tumor, Protocol Specific
- What is being tested?
- wild-type reovirus, cyclophosphamide and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 27 sitesin 2 countries
- Study dates
- Dec 2010to Apr 2014
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with relapsed or refractory solid tumors, with the exception of central nervous system (CNS) tumors and lymphomas, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy and immunizations
- Must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
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- At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
- At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
- >= 2 weeks for local palliative radiation therapy (XRT) (small port); >= 24 weeks must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
- No evidence of active graft vs host disease and >= 12 weeks must have elapsed since stem cell transplant or infusion
- Patients must not have received any previous viral-based anti-neoplastic therapies
- Viral immunizations, including influenza, may not have been administered within 7 days prior to enrollment; Note: patients may not receive any viral immunizations after enrolling on study until 28 days post their last planned REOLYSIN infusion
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,000/mm^3 (transfusion independent (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
- Patients with known bone marrow metastatic disease will be eligible for study but not evaluable for hematologic toxicity (maximum of one per cohort); such patients must meet the blood counts above (may receive transfusions provided they are not be known to be refractory to red cell or platelet transfusion); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR serum creatinine based on age and/or gender as follows:
- 0.8 mg/dL (3 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
- Bilirubin (sum of conjugated plus unconjugated) =< 1.5 x upper limit of normal (ULN) for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
- Serum albumin >= 2 g/dL
- Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by gated radionuclide study
- Normal pulmonary function tests (PFTs) (including diffusion capacity of carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); for patients who do not have respiratory symptoms, full PFTs are NOT required
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
- Nervous system disorders National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4 (CTCAE v. 4) resulting from prior therapy must be =< grade 2
- All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Who cannot join
- Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients who have an uncontrolled infection are not eligible
- Patients with chronic diarrhea, urinary incontinence during the day or at night, or patients who are not completely toilet trained will not be eligible
- Patients will be excluded if they have household contacts who are pregnant, immunosuppressed or infants less than 3 months of age; household contacts are defined as anyone living with the patient during the isolation period of the treatment cycles
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with known human immunodeficiency virus (HIV) or hepatitis B or C are excluded due to risk of viral infectivity of REOLYSIN; therefore, patients with a pre-existent infection are not eligible
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- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial
- Patients must not have received corticosteroids, immune modulators or antiviral therapy for 7 days prior to enrollment and must not have an anticipated need for any of these therapies, intravenous immune globulin (IVIG) must not have been administered within 2 weeks prior to enrollment
- Patients should avoid taking acetaminophen with REOLYSIN; whenever suitable, physicians should utilize alternative medications
- Patients with known germline mutations affecting Ras activation (e.g. NF-1, Cardio-facial-cutaneous syndrome, Noonan syndrome, Costello syndrome) will be excluded from enrollment
- Patients with known metastatic CNS disease involvement are excluded
- Patients with primary CNS tumors are excluded
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
United States25 sites
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Cook Children's Medical Center
Fort Worth, Texas, 76104
Baylor College of Medicine
Houston, Texas, 77030
Indiana University Medical Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, 32207-8426
Children's Hospital Los Angeles
Los Angeles, California, 90027
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455
Columbia University Medical Center
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Childrens Hospital of Orange County
Orange, California, 92868-3874
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Montefiore Medical Center
The Bronx, New York, 10467-2490
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Canada2 sites
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors
This phase I trial studies the side effects and the best dose of viral therapy in treating young patients with solid tumors that have come back or that have not responded to standard therapy. Some tumors have cells with a genetic weakness that makes them unable to fight off a virus called wild-type reovirus. The virus causes cells with this weakness to die, and may therefore be able to kill tumor cells without damaging normal cells. Cyclophosphamide is a drug used in chemotherapy that stops tumor cells from dividing and causes them to die. Giving wild-type reovirus together with cyclophosphamide may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REOLYSIN (wild-type reovirus) administered as an intravenous infusion daily for 5 days, every 28 days to children with relapsed or refractory solid tumors.
II. To define and describe the toxicities of Reolysin in these patients. III. To define the toxicity and tolerability of combining Reolysin with oral cyclophosphamide in these patients.
IV. To characterize the pharmacokinetics (time course of viral clearance) of Reolysin in children with refractory cancer.
SECONDARY OBJECTIVES:
- To define the antitumor activity of Reolysin within the confines of a phase I study.
II. To evaluate the development of neutralizing antibodies to Reolysin following intravenous administration of Reolysin alone and in combination with cyclophosphamide.
III. To assess the biologic activity of Reolysin.
OUTLINE: This is a dose-escalation study of wild-type reovirus.
Patients receive wild-type reovirus intravenously (IV) over 60 minutes once daily (QD) on days 1-5. Some patients also receive cyclophosphamide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 1 year.
- Being tested
- wild-type reovirus, cyclophosphamide, laboratory biomarker analysis, pharmacological study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
wild-type reovirusBiological
Also called REOLYSIN
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given PO
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (virus and chemotherapy) | Experimental | Patients receive wild-type reovirus IV over 60 minutes QD on days 1-5. Some patients also receive cyclophosphamide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: wild-type reovirus; Drug: cyclophosphamide; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated dose (MTD), defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT), graded using the NCI CTCAE v. 4.0
Measured: Up to 28 days
Secondary outcomes (3)
Time course of viral clearance of wild-type reovirus
Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Measured: Up to 3 months
Development of neutralizing antibodies to wild-type reovirus
Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Measured: Up to 3 months
Disease response, assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)
Will be reported descriptively.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study startDec 2010
- Primary completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Childhood Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- E. Anders Kolb, Principal investigator, COG Phase I Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01240538
- Sponsor's protocol ID
- NCI-2011-02617
- Other IDs
- NCI-2011-02617, CDR0000688938, ADVL1014, ADVL1014, U01CA097452
- Status last verified
- Jan 2014
- First submitted
- 11 Nov 2010
- Last updated
- 13 May 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT01240538
- Acronym / sponsor ID
- NCI-2011-02617
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2010
- Primary completion
- Apr 2014 (actual)
- First posted
- 15 Nov 2010 (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.
This phase I trial studies the side effects and the best dose of viral therapy in treating young patients with solid tumors that have come back or that have not responded to standard therapy. Some tumors have cells with a genetic weakness that makes them unable to fight off a virus called wild-type reovirus. The virus causes cells with this weakness to die, and may therefore be able to kill tumor cells without damaging normal cells. Cyclophosphamide is a drug used in chemotherapy that stops tumor cells from dividing and causes them to die. Giving wild-type reovirus together with cyclophosphamide may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REOLYSIN (wild-type reovirus) administered as an intravenous infusion daily for 5 days, every 28 days to children with relapsed or refractory solid tumors.
II. To define and describe the toxicities of Reolysin in these patients. III. To define the toxicity and tolerability of combining Reolysin with oral cyclophosphamide in these patients.
IV. To characterize the pharmacokinetics (time course of viral clearance) of Reolysin in children with refractory cancer.
SECONDARY OBJECTIVES:
- To define the antitumor activity of Reolysin within the confines of a phase I study.
II. To evaluate the development of neutralizing antibodies to Reolysin following intravenous administration of Reolysin alone and in combination with cyclophosphamide.
III. To assess the biologic activity of Reolysin.
OUTLINE: This is a dose-escalation study of wild-type reovirus.
Patients receive wild-type reovirus intravenously (IV) over 60 minutes once daily (QD) on days 1-5. Some patients also receive cyclophosphamide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (virus and chemotherapy) | Experimental | Biological: wild-type reovirus, Drug: cyclophosphamide, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive wild-type reovirus IV over 60 minutes QD on days 1-5. Some patients also receive cyclophosphamide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (31 listed)
- Patients with relapsed or refractory solid tumors, with the exception of central nervous system (CNS) tumors and lymphomas, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy and immunizations
Key exclusion criteria (14 listed)
- Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients who have an uncontrolled infection are not eligible
- Patients with chronic diarrhea, urinary incontinence during the day or at night, or patients who are not completely toilet trained will not be eligible
- Patients will be excluded if they have household contacts who are pregnant, immunosuppressed or infants less than 3 months of age; household contacts are defined as anyone living with the patient during the isolation period of the treatment cycles
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
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 |
|---|---|---|
| wild-type reovirusAlso: REOLYSINGiven IV | Biological | Treatment (virus and chemotherapy) |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven PO | Drug | Treatment (virus and chemotherapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (virus and chemotherapy) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (virus and chemotherapy) |
Primary outcome
Maximum-tolerated dose (MTD), defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT), graded using the NCI CTCAE v. 4.0
Time frame: Up to 28 days
3 secondary outcomes
Time course of viral clearance of wild-type reovirus
Time frame: Up to 3 months
Development of neutralizing antibodies to wild-type reovirus
Time frame: Up to 3 months
Disease response, assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 1 year
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 13 May 2014.
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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.
E. Anders Kolb principal investigator
COG Phase I Consortium
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing wild-type reovirus, cyclophosphamide and laboratory biomarker analysis in people with Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 27 sites in 2 countries.
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 31 inclusion and 14 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 13 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada. 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?
Maximum-tolerated dose (MTD), defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT), graded using the NCI CTCAE v. 4.0 (time frame: Up to 28 days). 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 13 May 2014.