Rhabdomyosarcoma and Other Soft Tissue SarcomasPhase 1NCT01518413
Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Solid Tumors
A Phase 1 study testing sorafenib and irinotecan in people with Rhabdomyosarcoma and Other Soft Tissue Sarcomas and Ewing's Sarcoma Family of Tumors, run by HMeany at 4 sites in United States.
Trial summary
The purpose of this study is to determine the safest and most effective oral dose combinations of sorafenib and irinotecan in pediatric patients with solid tumors, i.e. relapsed or refractory. Read more about this study
- Who is it for?
- Ages 2 to 22 years
- Conditions the study is for
- Rhabdomyosarcoma and Other Soft Tissue Sarcomas, Ewing's Sarcoma Family of Tumors, Osteosarcoma
- What is being tested?
- sorafenib and irinotecan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2011to Jan 2015
- 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 2 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- AGE: >=2 year and <22 years of age.
- DIAGNOSIS: solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors and brain tumors.
- MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable disease.
- THERAPEUTIC OPTIONS:
- The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
- PRIOR THERAPY:
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- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrolling on this study.
- No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study enrollment.
- Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.
- Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.
- Biologic (anti-cancer agent): The last dose of all biologic agents for the treatment of the patient's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 7 days prior to study entry. 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.
- Investigational anti-cancer agent: The last dose of all investigational agents must be at least 30 days prior to study entry.
- Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.
- Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant or at least 3 months post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease.
- Prior camptothecins: Patients who previously received irinotecan as front line treatment or in an adjuvant setting are eligible if they did not experience severe toxicities (defined as grade 4 non-hematologic toxicity or failure to recover from any non-hematologic or hematologic toxicity within 6 weeks of receiving the drug) possibly, probably or definitely related to the agent, and they did not experience tumor progression during the time they received the agent. Patients who previously received topotecan are eligible.
- Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.
- CONCURRENT THERAPIES:
- No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) is permitted.
- PERFORMANCE STATUS:
- Patients > 10 years old must have a Karnofsky performance level >= 50%, and children <= 10 years old must have a Lansky performance level >= 50%.
- Patients who are unable to walk because of paralysis or motor weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
- HEMATOLOGIC FUNCTION:
- Peripheral absolute neutrophil count (ANC) of >=750/mcL
- Platelet count >=75,000/mcL without administration of platelets
- HEPATIC FUNCTION:
- Total bilirubin must be gender
- SGPT (ALT) must be - Serum albumin >/= 2 g/dL
- RENAL FUNCTION: Age-adjusted normal serum creatinine (see table below) OR a creatinine clearance >=60 mL/min/1.73 m2. Age Maximum Serum Creatinine (Years) (mg/dl) Male Female 2 to less than 6 years 0.8 0.8 6 to less than 10 years 1 1 10 to less than 13 years 1.2 1.2 13 years to less than 16 years 1.5 1.4 Greater than or equal to 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz et.al. J Peds 106:522, 1985) utilizing child length and stature data published by the CDC.
- ADEQUATE PULMONARY FUNCTION: Defined as no dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air if there is clinical indication for determination (cough, etc).
- Normal serum amylase and lipase
- PT and PTT <= 1.5 times the upper limit of normal for age (including patients on prophylactic anticoagulation). Prophylactic anticoagulation as described below is permitted:
- Low dose warfarin with PT-INR <= 1.5 x ULN. For subjects receiving warfarin, the PT-INR should be measured prior to initiation of trial drugs and should be monitored at least weekly, or as defined by the local standard of care, until it is stable.
- Low-dose aspirin (<= 100 mg daily).
- Prophylactic doses of heparin.
- Blood pressure (BP) <= the 95th percentile for age, height and gender and not receiving anti-hypertensive medications or well controlled on antihypertensive medications for one week. Blood pressure will be recorded as the average of 2 measurements separated by at least 2 minutes. If the second value is more than 5 mmHg different from the first, continued measurements should be made every 2 minutes until a stable value is attained. The recorded value should be the average of the last two measurements obtained. Blood pressure is to be measured preferably in the right arm with an appropriate sized cuff, taken in a seated position after 3 minutes of rest. Oscillometric blood pressure measurements that exceed the 95th percentile should be confirmed by auscultation.
- BIRTH CONTROL: Patients of childbearing or child-fathering potential will be required and must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
Who cannot join
- Clinically significant unrelated systemic illness, such as serious infections, hepatic,renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate the agents used in this trial or are likely to interfere with the study procedures or results.
- Patients with known intra-axial metastatic central nervous system lesions.
- Pregnant or breast-feeding females are excluded because of the potential harmful effects of sorafenib and irinotecan on a developing fetus or nursing child.
- Patients currently receiving other anticancer agents or radiation therapy.
- Patients currently receiving other investigational agents.
- Prior treatment with a sorafenib containing regimen.
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- Inability to swallow pills.
- Evidence of bleeding diathesis and/or on therapeutic anti-coagulation medications.
- Patients with known Gilbert syndrome.
- Patients who take cytochrome P450 enzyme-inducing antiepileptic agents (phenytoin, carbamazepine, phenobarbitol), rifampin, erythromycin, azithromycin, azole antifungals, grape fruit juice or St. Johns Wort. Patients must have discontinued these medications at least 7 days prior to enrollment of trial.
- Patients with baseline hypertension (>=95th BP percentile for age, height and gender) and not controlled on anti-hypertensive medications.
- Patients with a malabsorption syndrome.
- Patients with known human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection.
- Patients with serious non-healing wound, ulcer, or bone fracture.
- Patients with thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Patients with cardiac ventricular arrhythmias requiring anti-arrhythmic therapy,unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- Patients who have undergone major surgery, open biopsy or significant traumatic injury within 4 weeks of study enrollment.
- Patients with known or suspected allergy to any agent given in the course of this trial.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
National Cancer Institute
Bethesda, Maryland, 20892
Children's Hospital Boston/Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Phase 1 Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Relapsed or Refractory Solid Tumors
The purpose of this study is to determine the safest and most effective oral dose combinations of sorafenib and irinotecan in pediatric patients with solid tumors, i.e. relapsed or refractory.
Read the detailed description
Sorafenib, a multi-kinase inhibitor of several targets felt to be important in tumor growth and angiogenesis, has been well studied and shown promising clinical results in adult cancer patients and the Maximum Tolerated Dose or MTD has been determined in pediatric patients. Irinotecan is known to be effective and is widely used in pediatric malignancies. The combination of sorafenib with irinotecan is of interest as these agents have different mechanisms of action. In addition, the combination has been evaluated in adult patients and deemed tolerable without alterations in the pharmacokinetic (PK) profile at the MTD. The trial we are proposing also offers the advantage of being a completely oral regimen, adding convenience and cost effectiveness. Given these considerations, if the sorafenib/irinotecan combination proves tolerable in phase I studies and shows efficacy in phase II studies, it would be an attractive combination to incorporate into existing chemotherapy regimens for pediatric cancer.
- Conditions
- Rhabdomyosarcoma and Other Soft Tissue Sarcomas, Ewing's Sarcoma Family of Tumors, Osteosarcoma, Neuroblastoma, Brain Tumors
- Being tested
- sorafenib, irinotecan
- Keywords
- Sora./Irino. combination therapy
- Medical subject headings
- Rhabdomyosarcoma, Osteosarcoma, Neuroblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenibDrug
sorafenib (50 and 200 mg tablets) orally twice daily, on a continuous schedule at a starting dose of 150mg/m2/dose.
irinotecanDrug
irinotecan (70 mg/m2/dose) orally, concurrently, once daily,starting at the beginning of the 21 day cycle,repeated every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | Three to 6 patient will be enrolled at each dose level and dose escalations will proceed in the absence of dose-limiting toxicity attributed to therapy, first with dose escalation of sorafenib and then, if tolerated, escalation of irinotecan. Receives: Drug: sorafenib; Drug: irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity Profile
Determine the toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of sorafenib, when administered in combination with oral irinotecan in children with relapsed or refractory solid tumors.
Measured: 24 months
Patient Related Outcomes
Demonstrate the feasibility of incorporating measurement of patient-related outcome into a four site phase 1 trial of sorafenib and irinotecan for children and adolescents.
Demonstrate feasibility: defined as 70% of participants will complete the 5 patient-reported outcomes (PROs) (pain, fatigue, worry, sadness and physical functioning) at both baseline (pre-treatment) and at the end of the first course and missing data will not be greater than 15% across the 5 PROs at either data point.
Measured: 24 months
Secondary outcomes (3)
Pharmacokinetic Profile
Describe the plasma pharmacokinetic profile of sorafenib and irinotecan when administered as combination therapy in children and adolescents.
Measured: 24 months
Disease Evaluation
Evaluate disease response, based on criteria for measurable lesions (RECIST) and evaluable lesions, to guide further development in phase 2 studies.
Measured: 24 months
Integration of Patient Related Outcomes with other outcome measures
Correlate and integrate the PRO scores with traditional endpoints of toxicity, pharmacokinetic profile, and tumor response associated with the sorafenib and irinotecan combination.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2012 (estimated)
- Study startDec 2011
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rhabdomyosarcoma and Other Soft Tissue SarcomasStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- HMeany
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, HMeany, Children's National Research Institute
- Investigators
- Holly Meany, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01518413
- Sponsor's protocol ID
- SorIrin1576
- Status last verified
- Feb 2015
- First submitted
- 4 Jan 2012
- Last updated
- 27 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Meany HJ, Widemann BC, Hinds PS, Bagatell R, Shusterman S, Stern E, Jayaprakash N, Peer CJ, Figg WD, Hall OM, Sissung TM, Kim A, Fox E, London WB, Rodriguez-Galindo C, Minturn JE, Dome JS. Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors. Pediatr Blood Cancer. 2021 Nov;68(11):e29282. doi: 10.1002/pbc.29282. Epub 2021 Aug 12.
PubMed 34383370
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT01518413
- Acronym / sponsor ID
- SorIrin1576
- Conditions
- Rhabdomyosarcoma and Other Soft Tissue Sarcomas, Ewing's Sarcoma Family of Tumors, Osteosarcoma, Neuroblastoma, Brain Tumors
- Keywords
- Sora./Irino. combination therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- HMeanyUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 26 Jan 2012 (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 study is to determine the safest and most effective oral dose combinations of sorafenib and irinotecan in pediatric patients with solid tumors, i.e. relapsed or refractory.
Detailed description
Sorafenib, a multi-kinase inhibitor of several targets felt to be important in tumor growth and angiogenesis, has been well studied and shown promising clinical results in adult cancer patients and the Maximum Tolerated Dose or MTD has been determined in pediatric patients. Irinotecan is known to be effective and is widely used in pediatric malignancies. The combination of sorafenib with irinotecan is of interest as these agents have different mechanisms of action. In addition, the combination has been evaluated in adult patients and deemed tolerable without alterations in the pharmacokinetic (PK) profile at the MTD. The trial we are proposing also offers the advantage of being a completely oral regimen, adding convenience and cost effectiveness. Given these considerations, if the sorafenib/irinotecan combination proves tolerable in phase I studies and shows efficacy in phase II studies, it would be an attractive combination to incorporate into existing chemotherapy regimens for pediatric cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Drug: sorafenib, Drug: irinotecanThree to 6 patient will be enrolled at each dose level and dose escalations will proceed in the absence of dose-limiting toxicity attributed to therapy, first with dose escalation of sorafenib and then, if tolerated, escalation of irinotecan. |
Who may qualify
- Ages
- 2 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (36 listed)
- AGE: >=2 year and <22 years of age.
- The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrolling on this study.
- No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study enrollment.
- Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.
Key exclusion criteria (18 listed)
- Clinically significant unrelated systemic illness, such as serious infections, hepatic,renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate the agents used in this trial or are likely to interfere with the study procedures or results.
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 |
|---|---|---|
| sorafenibsorafenib (50 and 200 mg tablets) orally twice daily, on a continuous schedule at a starting dose of 150mg/m2/dose. | Drug | Combination Therapy |
| irinotecanirinotecan (70 mg/m2/dose) orally, concurrently, once daily,starting at the beginning of the 21 day cycle,repeated every 21 days | Drug | Combination Therapy |
Primary outcome
Toxicity Profile
Time frame: 24 months
Determine the toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of sorafenib, when administered in combination with oral irinotecan in children with relapsed or refractory solid tumors.
Patient Related Outcomes
Time frame: 24 months
Demonstrate the feasibility of incorporating measurement of patient-related outcome into a four site phase 1 trial of sorafenib and irinotecan for children and adolescents. Demonstrate feasibility: defined as 70% of participants will complete the 5 patient-reported outcomes (PROs) (pain, fatigue, worry, sadness and physical functioning) at both baseline (pre-treatment) and at the end of the first course and missing data will not be greater than 15% across the 5 PROs at either data point.
3 secondary outcomes
Pharmacokinetic Profile
Time frame: 24 months
Disease Evaluation
Time frame: 24 months
Integration of Patient Related Outcomes with other outcome measures
Time frame: 24 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 27 Feb 2015.
- Derived from this study: PubMed 34383370Meany HJ, Widemann BC, Hinds PS, Bagatell R, Shusterman S, Stern E, Jayaprakash N, Peer CJ, Figg WD, Hall OM, Sissung TM, Kim A, Fox E, London WB, Rodriguez-Galindo C, Minturn JE, Dome JS. Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors. Pediatr Blood Cancer. 2021 Nov;68(11):e29282. doi: 10.1002/pbc.29282. Epub 2021 Aug 12.
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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.
Holly Meany, MD principal investigator
Children's National Research Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sorafenib and irinotecan in people with Rhabdomyosarcoma and Other Soft Tissue Sarcomas and Ewing's Sarcoma Family of Tumors, run by HMeany at 4 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 36 inclusion and 18 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 27 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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?
Toxicity Profile (time frame: 24 months). 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?
On the ClinicalTrials.gov record for NCT01518413, which also lists 1 linked publication.
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 27 Feb 2015.