Previously Treated Childhood RhabdomyosarcomaPhase 1NCT00077454
Erlotinib and Temozolomide in Treating Young Patients With Recurrent or Refractory Solid Tumors
A Phase 1 study testing erlotinib hydrochloride, temozolomide and pharmacological study in people with Previously Treated Childhood Rhabdomyosarcoma and Recurrent Childhood Brain Tumor, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of erlotinib when given with temozolomide in treating young patients with recurrent or refractory solid tumors. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma
- What is being tested?
- erlotinib hydrochloride, temozolomide and pharmacological study
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2004to Sep 2007
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- One of the following histologically confirmed solid tumors:
- Brain tumors
- Osteogenic sarcoma
- Rhabdomyosarcoma
- Soft tissue sarcoma (excluding Ewing's sarcoma)
- Neuroblastoma
Show all 59Show fewer
- Germ cell tumors
- Recurrent or refractory disease
- No known curative therapy exists
- Performance status - Karnofsky 50-100% (for patients age 11 to 21)
- Performance status - Lansky 50-100% (for patients age 10 and under)
- At least 8 weeks
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3 (transfusion independent*)
- Hemoglobin > 8.0 g/dL (transfusion allowed)
- Bilirubin < 1.5 times upper limit of normal (ULN)
- ALT < 2.5 times ULN
- Albumin ≥ 2 g/dL
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- Creatinine based on age as follows:
- ≤ 0.8 mg/dL for patients age 5 and under
- ≤ 1.0 mg/dL for patients 6 to 10
- ≤ 1.2 mg/dL for patients 11 to 15
- ≤ 1.5 mg/dL for patients age 15 to 21
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to swallow tablets (for patients in part 2 only)
- No uncontrolled infection
- Recovered from all prior immunotherapy
- At least 7 days since prior biologic therapy
- At least 3 months since prior stem cell transplantation and no evidence of active graft-versus-host disease
- More than 1 week since prior growth factors
- No concurrent prophylactic growth factor therapy
- No concurrent immunotherapy
- No concurrent biologic therapy
- More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
- No other concurrent chemotherapy
- No concurrent systemic corticosteroids except for treatment of increased intracranial pressure or symptomatic tumor edema in patients with CNS tumors
- No concurrent steroids as an antiemetic
- Concurrent dexamethasone for patients with CNS tumors allowed provided patient has been on a stable or decreasing dose for at least 1 week before study entry
- Recovered from all prior radiotherapy
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 weeks since prior substantial bone marrow irradiation
- At least 6 months since prior craniospinal radiotherapy
- At least 6 months since prior radiotherapy to 50% or more of the pelvis
- At least 8 weeks since prior standard-fraction radiotherapy for patients with recurrent brain tumors unless there is biopsy proof of recurrent tumor
- Prior radiosurgery within the past 9 months allowed provided there is documentation of progressive disease by biopsy, positron-emission tomography (PET) scan, or MR spectroscopy
- No concurrent radiotherapy
- More than 1 week since prior CYP3A4 inhibitors
- More than 4 weeks since prior CYP3A4 inducers
- More than 5 days since prior proton-pump inhibitors
- More than 2 days since prior H_2 blockers
- No prior erlotinib
- No concurrent enzyme-inducing anticonvulsants
- No concurrent proton-pump inhibitors
- No concurrent H2 blockers
- No other concurrent investigational agents
- Concurrent antacids allowed provided the antacid is not administered 2 hours before, during, and 2 hours after erlotinib administration
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
COG Phase I Consortium
Arcadia, California, 91006-3776
About this study
Official title: A Phase I Study of Single Agent OSI-774 (Tarceva) (NSC# 718781, IND# 63383) Followed by OSI-774 With Temozolomide for Patients With Selected Recurrent/Refractory Solid Tumors, Including Brain Tumors
This phase I trial is studying the side effects and best dose of erlotinib when given with temozolomide in treating young patients with recurrent or refractory solid tumors. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving erlotinib with temozolomide may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of erlotinib in children with recurrent or refractory solid tumors.
II. Determine the dose-limiting toxic effects of this drug alone and with temozolomide in these patients.
III. Determine the tolerability of this regimen in these patients. IV. Determine the pharmacokinetics of this regimen in these patients.
SECONDARY OBJECTIVES:
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a 2-part, multicenter, dose-escalation study of erlotinib. Patients are stratified according to pretreatment (heavily pretreated [received more than 2 prior multiagent myelosuppressive chemotherapy regimens OR received prior craniospinal or pelvic radiotherapy or bone marrow transplantation OR has bone marrow involvement] vs less heavily pretreated).Part 1:
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib during course 1 only until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Part 2: Patients receive erlotinib (at the MTD) and temozolomide as in part 1.
PROJECTED ACCRUAL: A total of 9-45 patients (9-24 for part 1 and up to 21 for part 2) will be accrued for this study.
- Conditions
- Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Malignant Germ Cell Tumor
- Being tested
- erlotinib hydrochloride, temozolomide, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Astrocytoma, Familial ependymoma, Medulloblastoma, Neuroblastoma, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
Also called CP-358,774, erlotinib, OSI-774
Given orally (PO)
temozolomideDrug
Also called SCH 52365, Temodal, Temodar, TMZ
Given PO
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (erlotinib hydrochloride, temozolomide) | Experimental | Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: erlotinib hydrochloride; Drug: temozolomide; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Measured: 56 days (2 courses)
Maximum-tolerated dose (MTD) based on the incidence of DLT as assessed by NCI CTCAE version 3.0
Measured: 56 days (2 courses)
Pharmacokinetics of erlotinib hydrochloride
Measured: At baseline and at 0.5, 1, 2, 4, 6, 8, and 24 hours of course 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2004 (estimated)
- Study startFeb 2004
- Primary completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Previously Treated Childhood RhabdomyosarcomaStudies 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
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Regina Jakacki, Principal investigator, COG Phase I Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00077454
- Sponsor's protocol ID
- NCI-2012-01808
- Other IDs
- ADVL0214, CDR0000350336, COG-ADVL0214, NCI-04-C-0256, U01CA097452
- Status last verified
- Jun 2013
- First submitted
- 10 Feb 2004
- Last updated
- 5 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Single Agent OSI-774 (Tarceva) (NSC# 718781, IND# 63383) Followed by OSI-774 With Temozolomide for Patients With Selected Recurrent/Refractory Solid Tumors, Including Brain Tumors
- ClinicalTrials.gov ID
- NCT00077454
- Acronym / sponsor ID
- NCI-2012-01808
- Conditions
- Previously Treated Childhood Rhabdomyosarcoma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Malignant Germ Cell Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2004
- Primary completion
- Sep 2007 (actual)
- First posted
- 12 Feb 2004 (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 is studying the side effects and best dose of erlotinib when given with temozolomide in treating young patients with recurrent or refractory solid tumors. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving erlotinib with temozolomide may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of erlotinib in children with recurrent or refractory solid tumors.
II. Determine the dose-limiting toxic effects of this drug alone and with temozolomide in these patients.
III. Determine the tolerability of this regimen in these patients. IV. Determine the pharmacokinetics of this regimen in these patients.
SECONDARY OBJECTIVES:
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is a 2-part, multicenter, dose-escalation study of erlotinib. Patients are stratified according to pretreatment (heavily pretreated [received more than 2 prior multiagent myelosuppressive chemotherapy regimens OR received prior craniospinal or pelvic radiotherapy or bone marrow transplantation OR has bone marrow involvement] vs less heavily pretreated).Part 1:
Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib during course 1 only until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Part 2: Patients receive erlotinib (at the MTD) and temozolomide as in part 1.
PROJECTED ACCRUAL: A total of 9-45 patients (9-24 for part 1 and up to 21 for part 2) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (erlotinib hydrochloride, temozolomide) | Experimental | Drug: erlotinib hydrochloride, Drug: temozolomide, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (59 listed)
- One of the following histologically confirmed solid tumors:
- Recurrent or refractory disease
- No known curative therapy exists
- Performance status - Karnofsky 50-100% (for patients age 11 to 21)
- Performance status - Lansky 50-100% (for patients age 10 and under)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| erlotinib hydrochlorideAlso: CP-358,774, erlotinib, OSI-774Given orally (PO) | Drug | Treatment (erlotinib hydrochloride, temozolomide) |
| temozolomideAlso: SCH 52365, Temodal, Temodar, TMZGiven PO | Drug | Treatment (erlotinib hydrochloride, temozolomide) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (erlotinib hydrochloride, temozolomide) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (erlotinib hydrochloride, temozolomide) |
Primary outcome
Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time frame: 56 days (2 courses)
Maximum-tolerated dose (MTD) based on the incidence of DLT as assessed by NCI CTCAE version 3.0
Time frame: 56 days (2 courses)
Pharmacokinetics of erlotinib hydrochloride
Time frame: At baseline and at 0.5, 1, 2, 4, 6, 8, and 24 hours of course 1
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 5 Jun 2013.
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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.
Regina Jakacki principal investigator
COG Phase I Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing erlotinib hydrochloride, temozolomide and pharmacological study in people with Previously Treated Childhood Rhabdomyosarcoma and Recurrent Childhood Brain Tumor, run by National Cancer Institute (NCI) at 1 site 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 59 inclusion and 0 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 5 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (time frame: 56 days (2 courses)). The study lists 3 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 5 Jun 2013.