Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients With Solid Tumors

NCT01518413 | Completed Phase 1 DMC

• 1 other identifier: SorIrin1576
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Rhabdomyosarcoma and Other Soft Tissue Sarcomas; Ewing's Sarcoma Family of Tumors; Osteosarcoma; Neuroblastoma; Brain Tumors

Keywords

Sora./Irino. combination therapy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  24 months

Secondary Outcomes (3)

• Pharmacokinetic Profile

  24 months

• Disease Evaluation

  24 months

• Integration of Patient Related Outcomes with other outcome measures

  24 months

Study Arms (1)

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.

Drug: sorafenib; Drug: irinotecan

Interventions

sorafenib DRUG

sorafenib (50 and 200 mg tablets) orally twice daily, on a continuous schedule at a starting dose of 150mg/m2/dose.

Combination Therapy

irinotecan DRUG

irinotecan (70 mg/m2/dose) orally, concurrently, once daily,starting at the beginning of the 21 day cycle,repeated every 21 days

Combination Therapy

Eligibility Criteria

• Age: 2 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• HMeany: lead

Study Sites (4)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Children's Hospital Boston/Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 34383370 DERIVED

MeSH Terms

Conditions

Rhabdomyosarcoma; Osteosarcoma; Neuroblastoma; Brain Neoplasms

Interventions

Sorafenib; Irinotecan

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids

Study Officials

• Holly Meany, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Holly Meany, MD

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 26, 2012
• Study Start: December 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: February 27, 2015

Record last verified: 2015-02

Locations

US (4)