Childhood CraniopharyngiomaPhase 2NCT01964300
Peginterferon Alfa-2b in Younger Patients With Craniopharyngioma That is Recurrent or Cannot Be Removed By Surgery
A Phase 2 study testing peginterferon alfa-2b and laboratory biomarker analysis in people with Childhood Craniopharyngioma, run by Pediatric Brain Tumor Consortium at 9 sites in United States.
Trial summary
This phase II trial studies how well peginterferon alfa-2b works in treating younger patients with craniopharyngioma that is recurrent or cannot be removed by surgery. Peginterferon alfa-2b may interfere with the growth of tumor cells and slow the growth of craniopharyngioma. Read more about this study
- Who is it for?
- Ages 18 months to 25 years
- Conditions the study is for
- Childhood Craniopharyngioma
- What is being tested?
- peginterferon alfa-2b and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 9 sitesUnited States
- Study dates
- 1 Apr 2014to 1 Jan 2019
- 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 months to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient must have a histologically verified diagnosis of craniopharyngioma
- Stratum 1: patients with progressive unresectable or recurrent craniopharyngiomas treated with surgery alone, who have not received radiation therapy; patients with unresectable craniopharyngiomas, (i.e. residual measurable disease following surgical resection) will be enrolled at the time of progression
- Stratum 2: patients with progressive or recurrent craniopharyngiomas following radiation therapy
- All patients must have measurable residual disease defined as tumor measurable in two perpendicular diameters on magnetic resonance imaging (MRI)
- Please note: measurements are required for both the solid and cystic components
- Subjects must have recovered from the acute toxicities of all prior therapy before entering this study; for those acute baseline adverse events attributable to prior therapy, recovery is defined as a toxicity grade =< 2, using Common Terminology Criterial for Adverse Events (CTCAE) version (v.) 4.0, unless otherwise specified in the inclusion and exclusion criteria
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- Myelosuppressive chemotherapy (includes intra-cystic bleomycin):
- Subjects must have received their last dose of known myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration or at least six (6) weeks if nitrosourea
- Subjects must have received their last dose of investigational or biologic agent >= 7 days prior to study registration
- In the event that a subject has received an investigational or biologic agent and has experienced >= grade 2 myelosuppression, then at least three (3) weeks must have elapsed prior to registration
- If the investigational or biologic agent has a prolonged half-life (>= 7 days) then at least three (3) weeks must have elapsed prior to registration
- Subjects must have completed at least 3 half-life periods from the last dose of monoclonal antibody prior to registration
- Note: a list of half-lives of commonly used monoclonal antibodies is available on the Pediatric Brain Tumor Consortium (PBTC) website under Generic Forms and Templates
- Stratum 1: patients must not have received radiation therapy
- Stratum 2: patients must have received radiation therapy, including gamma knife or phosphorus-32 (P32)
- More than 6 months from the time of enrollment if the recurrence is predominantly solid
- More than 12 months from the time of enrollment if the recurrence is predominantly cystic
- At least 7 days since the completion of therapy with a hematopoietic growth agent (filgrastim, sargramostim, and erythropoietin) and 14 days for long-acting formulations
- Karnofsky performance scale (KPS for > 16 years [yrs] of age) or Lansky performance score (LPS for =< 16 years of age) >= 60 assessed within two weeks prior to registration
- Age: 18 months - 25 years (Minimum weight 20 Kilogram is required to be eligible for the study, since the minimum injection volume of SYLATRON is 0.05 ml, 20 mcg, subcutaneously (SQ) as suggested by Merck)
- Absolute neutrophil count (ANC) >= 1000/ul (unsupported)
- Platelets >= 100,000/ul (unsupported)
- Hemoglobin (Hg) >= 8g/dL (unsupported)
- Alanine aminotransferase (ALT) =< 2.5 x the upper limit of institutional normal
- Total bilirubin =< x 1.5 upper limit of institutional normal
- Serum creatinine =< 1.5 x the upper limit of normal for age, or calculated creatinine clearance or nuclear glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2
- =< 0.6 mg/dL (1 to < 2 years of age)
- =< 0.8 mg/dL (2 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)
- =< 1.4 mg/dL (females >= 13 years of age)
- =< 1.5 mg/dL (males 13 to < 16 years of age)
- =< 1.7 mg/dL (males >= 16 years of age)
- All patients must have undergone at least one surgical procedure to verify the diagnosis
- Patients must have evidence of radiographic progression as defined below:
- Stratum 1: defined as >= 25% increase in the product of the greatest perpendicular diameters of the tumor as a whole (solid and cystic component) AND >= 0.4 cm increase in each of at least two dimensions of the tumor as a whole OR any new or worsening neurologic/vision deficit in conjunction with a lesser change in the solid or cystic component
- Stratum 2:
- For patients more than 6 months following radiation therapy (RT) (including radiosurgery or P32), progression is defined as a >= 25% increase in the product of the greatest perpendicular diameters of the solid component AND >= 0.4 cm increase in each of at least two dimensions of the solid component
- For patients more than 12 months following RT (including radiosurgery or P32), progression is defined as >= 25% increase in each of the product of the greatest perpendicular diameters of the solid tumor AND >= 0.4 cm increase in each of at least two dimensions of the solid tumor; patients demonstrating isolated cyst progression more than 12 months after RT must show a continued increase in the cystic component on two serial MRI scans performed at least 4 weeks apart OR re-accumulation of the cyst following one or more cyst aspirations; patients with progressive neurologic signs and/or symptoms associated with isolated cyst formation or progression are eligible if the neurologic signs and/or symptoms do not improve within 4 weeks of cyst aspiration
- Female subjects of childbearing potential must not be pregnant or breast-feeding; female subjects of childbearing potential must have a negative serum or urine pregnancy test; (pregnancy test must be repeated within 72 hours prior to the start of therapy)
- Subjects of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Stratum 1 patients: must not have had > 3 surgical debulking procedures/resections
- Patients may not have received prior interferon, either systemic or intra-cystic
- Patients must not have evidence of metastatic tumor
- Patients must not be on steroids other than for physiologic replacement
- Patients must not have a severe psychiatric illness, including major depression or any previous suicide attempts
- Patients must not be on phenytoin, warfarin or methadone due to potential drug interactions
- Patients must not have known hypersensitivity reactions, such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Steven-Johnson syndrome, and toxic epidermal necrolysis to interferon alpha or any other products component
- Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
National Cancer Institute Pediatric Oncology Branch
Bethesda, Maryland, 20892
Lurie Children's Hospital
Chicago, Illinois, 60614
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
St. Jude Children Research Hospital
Memphis, Tennessee, 38105
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stanford University and Lucile Packard Children Hospital
Palo Alto, California, 94304
Children Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Phase II Study of Peginterferon Alfa-2b (Sylatron) for Pediatric Patients With Unresectable or Recurrent Craniopharyngioma
This phase II trial studies how well peginterferon alfa-2b works in treating younger patients with craniopharyngioma that is recurrent or cannot be removed by surgery. Peginterferon alfa-2b may interfere with the growth of tumor cells and slow the growth of craniopharyngioma.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the 1-year disease stabilization rate associated with the use of Sylatron (peginterferon alfa-2b) in patients with progressive unresectable or recurrent craniopharyngiomas following surgery alone who have not received radiation therapy.
II. To estimate the sustained objective response rate (partial response (PR) + complete response (CR)) to Sylatron in patients with craniopharyngiomas which progress or recur following radiation therapy.
SECONDARY OBJECTIVES:
- To estimate the response rate in patients with progressive unresectable or recurrent craniopharyngioma treated with Sylatron by study stratum.
II. To estimate the progression-free survival distribution for patients with unresectable or recurrent craniopharyngiomas treated with Sylatron by study stratum.
III. To evaluate the toxicity profile of Sylatron in children with unresectable or recurrent craniopharyngiomas.
IV. To compare the protocol specific disease assessment criteria to MacDonald criteria during the first year of treatment in stratum I and at the time of objective response and progressive disease in both strata.
- To characterize evidence of WNT pathway activation by immunohistochemistry and MAPK pathway activation by pyrosequencing in resected tumor tissue in patients with craniopharyngiomas, and correlate these results with outcome and response data.
OUTLINE:
Patients receive peginterferon alfa-2b subcutaneously (SC) weekly for 6 weeks. Treatment may repeat every 6 weeks for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Childhood Craniopharyngioma
- Being tested
- peginterferon alfa-2b, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
peginterferon alfa-2bBiological
Given subcutaneously (SC)
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (peginterferon alfa-2b) | Experimental | Patients receive peginterferon alfa-2b subcutaneously (SC) weekly for 6 weeks. Treatment may repeat every 6 weeks for up to 18 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: peginterferon alfa-2b; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Disease Stabilization at 1 Year (i.e., 9 Courses of Treatment) (for Stratum 1 Patients Only)
The percentage of stratum 1 patients with disease stabilization at 1 year is reported, along with a 95% exact confidence interval for the estimate of the true 1-year disease stabilization rate.
Measured: Up to 1 year
Sustained Objective Response (PR+CR) Rate Observed During the First Year of Treatment (for Stratum 2 Patients Only)
Objective responses had to be sustained for 3 months. The percentage of participants with sustained objective responses is reported with an exact 95% confidence interval of the true sustained objective response rate.
Measured: Up to 1 year
Secondary outcomes (2)
Sustained Objective Response (PR+CR) Rate Observed During the First Year of Treatment (for Stratum 1 Patients Only)
Objective responses had to be sustained for 3 months. The percentage of participants with sustained objective responses is reported with an exact 95% confidence interval of the true sustained objective response rate.
Measured: Up to 1 year
Progression-free Survival (PFS)
PFS estimates for each stratum were estimated using the method of Kaplan and Meier. PFS was defined as the time interval from date on treatment to the earliest date of disease progression, second malignancy, or death; or to date of last contact for patients without events. One- and two-year PFS estimates are reported by stratum. Only eligible patients were included in this analysis (7 stratum 1 patients and 11 stratum 2 patients).
Measured: 2 years after treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2013 (estimated)
- Study start1 Apr 2014
- Primary completion1 Dec 2018
- Study completion1 Jan 2019
Why it stopped: Lack of efficacy (stratum 2); slow accrual (stratum 1)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Childhood CraniopharyngiomaStudies 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Stewart Goldman, Principal investigator, Ann & Robert H. Lurie Children Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01964300
- Sponsor's protocol ID
- PBTC-039
- Other IDs
- NCI-2013-01639, PBTC-039, PBTC-039, U01CA081457
- Status last verified
- Feb 2020
- First submitted
- 14 Oct 2013
- Last updated
- 24 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Peginterferon Alfa-2b (Sylatron) for Pediatric Patients With Unresectable or Recurrent Craniopharyngioma
- ClinicalTrials.gov ID
- NCT01964300
- Acronym / sponsor ID
- PBTC-039
- Conditions
- Childhood Craniopharyngioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy (stratum 2); slow accrual (stratum 1)
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Apr 2014 (actual)
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Jan 2019 (actual)
- First posted
- 17 Oct 2013 (estimated)
- Results
- Posted 24 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well peginterferon alfa-2b works in treating younger patients with craniopharyngioma that is recurrent or cannot be removed by surgery. Peginterferon alfa-2b may interfere with the growth of tumor cells and slow the growth of craniopharyngioma.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the 1-year disease stabilization rate associated with the use of Sylatron (peginterferon alfa-2b) in patients with progressive unresectable or recurrent craniopharyngiomas following surgery alone who have not received radiation therapy.
II. To estimate the sustained objective response rate (partial response (PR) + complete response (CR)) to Sylatron in patients with craniopharyngiomas which progress or recur following radiation therapy.
SECONDARY OBJECTIVES:
- To estimate the response rate in patients with progressive unresectable or recurrent craniopharyngioma treated with Sylatron by study stratum.
II. To estimate the progression-free survival distribution for patients with unresectable or recurrent craniopharyngiomas treated with Sylatron by study stratum.
III. To evaluate the toxicity profile of Sylatron in children with unresectable or recurrent craniopharyngiomas.
IV. To compare the protocol specific disease assessment criteria to MacDonald criteria during the first year of treatment in stratum I and at the time of objective response and progressive disease in both strata.
- To characterize evidence of WNT pathway activation by immunohistochemistry and MAPK pathway activation by pyrosequencing in resected tumor tissue in patients with craniopharyngiomas, and correlate these results with outcome and response data.
OUTLINE:
Patients receive peginterferon alfa-2b subcutaneously (SC) weekly for 6 weeks. Treatment may repeat every 6 weeks for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (peginterferon alfa-2b) | Experimental | Biological: peginterferon alfa-2b, Other: laboratory biomarker analysisPatients receive peginterferon alfa-2b subcutaneously (SC) weekly for 6 weeks. Treatment may repeat every 6 weeks for up to 18 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 months to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (42 listed)
- Patient must have a histologically verified diagnosis of craniopharyngioma
- All patients must have measurable residual disease defined as tumor measurable in two perpendicular diameters on magnetic resonance imaging (MRI)
- Subjects must have recovered from the acute toxicities of all prior therapy before entering this study; for those acute baseline adverse events attributable to prior therapy, recovery is defined as a toxicity grade =< 2, using Common Terminology Criterial for Adverse Events (CTCAE) version (v.) 4.0, unless otherwise specified in the inclusion and exclusion criteria
- Myelosuppressive chemotherapy (includes intra-cystic bleomycin):
- Subjects must have received their last dose of investigational or biologic agent >= 7 days prior to study registration
Key exclusion criteria (8 listed)
- Stratum 1 patients: must not have had > 3 surgical debulking procedures/resections
- Patients may not have received prior interferon, either systemic or intra-cystic
- Patients must not have evidence of metastatic tumor
- Patients must not be on steroids other than for physiologic replacement
- Patients must not have a severe psychiatric illness, including major depression or any previous suicide attempts
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 |
|---|---|---|
| peginterferon alfa-2bGiven subcutaneously (SC) | Biological | Treatment (peginterferon alfa-2b) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (peginterferon alfa-2b) |
Primary outcome
Rate of Disease Stabilization at 1 Year (i.e., 9 Courses of Treatment) (for Stratum 1 Patients Only)
Time frame: Up to 1 year
The percentage of stratum 1 patients with disease stabilization at 1 year is reported, along with a 95% exact confidence interval for the estimate of the true 1-year disease stabilization rate.
Sustained Objective Response (PR+CR) Rate Observed During the First Year of Treatment (for Stratum 2 Patients Only)
Time frame: Up to 1 year
Objective responses had to be sustained for 3 months. The percentage of participants with sustained objective responses is reported with an exact 95% confidence interval of the true sustained objective response rate.
2 secondary outcomes
Sustained Objective Response (PR+CR) Rate Observed During the First Year of Treatment (for Stratum 1 Patients Only)
Time frame: Up to 1 year
Progression-free Survival (PFS)
Time frame: 2 years after treatment start
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Childhood Craniopharyngioma
Enrolling by invitationObservational study
Prospective Pilot Study Identifying Clinically Relevant Biological Targets for Medical Therapy
Craniopharyngioma, Child
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.
Stewart Goldman principal investigator
Ann & Robert H. Lurie Children Hospital of Chicago
9 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 peginterferon alfa-2b and laboratory biomarker analysis in people with Childhood Craniopharyngioma, run by Pediatric Brain Tumor Consortium at 9 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 42 inclusion and 8 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 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
Yes. Results are posted in the registry (first posted 24 Feb 2020). 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?
Rate of Disease Stabilization at 1 Year (i.e., 9 Courses of Treatment) (for Stratum 1 Patients Only) (time frame: Up to 1 year). 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?
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 24 Feb 2020.