Phase 2
N=175
Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma
Adult Rhabdomyosarcoma · Childhood Alveolar Rhabdomyosarcoma · Childhood Embryonal Rhabdomyosarcoma · Metastatic Childhood Soft Tissue Sarcoma · Stage IV Adult Soft Tissue Sarcoma
Bottom Line
View on ClinicalTrials.gov: NCT01055314 ↗Enrolled (actual)
175
Serious AEs
71.7%
Results posted
Jul 2017
Primary outcome: Primary: Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment — 0.9390 Proportion of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cixutumumab (Biological); Cyclophosphamide (Drug); Dactinomycin (Biological); Doxorubicin Hydrochloride (Drug); Etoposide (Drug); Ifosfamide (Drug); Irinotecan Hydrochloride (Drug); Laboratory Biomarker Analysis (Other); Temozolomide (Drug); Vincristine Sulfate Liposome (Drug)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jun 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment |
0.9390 | — |
| PRIMARY Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment |
0.7097 | — |
| PRIMARY Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0 |
89; 61 | — |
| PRIMARY Event-Free Survival |
0.1627; 0.1919 | — |
| SECONDARY Response Rate (CR + PR) |
0.7667; 0.7846 | — |
Summary
This randomized pilot clinical trial is studying the side effects and how well giving temozolomide and cixutumumab together with combination chemotherapy works in treating patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temozolomide and cixutumumab together with combination chemotherapy may kill more tumor cells.
Eligibility Criteria
Inclusion Criteria
- Patients must be eligible for, and enrolled on D9902 prior to enrollment on ARST08P1
- Patients with newly diagnosed, biopsy-proven metastatic rhabdomyosarcoma or ectomesenchymoma (stage IV, clinical group IV) are eligible for this study; patients with stage IV, clinical group IV RMS with parameningeal and paraspinal primary tumors, including those with intracranial extension (ICE) are eligible for ARST08P1; ICE is defined by contrast magnetic resonance imaging (MRI) showing that the primary tumor touches, displaces, invades, distorts, or otherwise causes signal abnormality of the dura in brain or spinal cord in contiguity to the primary site; ICE is also presumed to exist if the cerebrospinal fluid (CSF) cytopathology is positive for tumor at diagnosis
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients = = 70 mL/min/1.73m^2 OR maximum serum creatinine based on age/gender as follows:
- 0.4 mg/dL (for patients 1 to 5 months of age)
- 0.5 mg/dL (for patients 6 to 11 months of age)
- 0.6 mg/dL (for patients 1 year of age)
- 0.8 mg/dL (for patients 2 to 5 years of age)
- 1.0 mg/dL (for patients 6 to 9 years of age)
- 1.2 mg/dL (for patients 10 to 12 years of age)
- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)
- Patients with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
- Total bilirubin = = 27% by echocardiogram (ECHO) OR ejection fraction >= 50% by radionuclide angiogram
- Absolute neutrophil count (ANC) >= 750/uL; abnormal blood counts are permissible if there is bone marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma
- Platelet count >= 75, 000/uL; abnormal blood counts are permissible if there is bone marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma
- Sexually active patients of childbearing potential must agree to use effective contraception during therapy (Pilots 1 and 2) and for at least 3 months after the last dose of IMC-A12 (Pilots 1)
Exclusion Criteria
- Female patients who are pregnant are not eligible
- Female patients who are breastfeeding are not eligible; female patients who are lactating must agree to stop breastfeeding to participate in this study
- Patients receiving growth hormone therapy are not eligible
- Patients with known type I or type II diabetes mellitus are not eligible for enrollment on Pilot 1
- Patients with evidence of uncontrolled infection are not eligible
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Data sourced from ClinicalTrials.gov (NCT01055314). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.