Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma
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| ClinicalTrials.gov Identifier: NCT01055314 |
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Recruitment Status :
Completed
First Posted : January 25, 2010
Results First Posted : July 28, 2017
Last Update Posted : August 29, 2017
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult Rhabdomyosarcoma Childhood Alveolar Rhabdomyosarcoma Childhood Embryonal Rhabdomyosarcoma Metastatic Childhood Soft Tissue Sarcoma Stage IV Adult Soft Tissue Sarcoma Untreated Childhood Rhabdomyosarcoma | Biological: Cixutumumab Drug: Cyclophosphamide Biological: Dactinomycin Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Ifosfamide Drug: Irinotecan Hydrochloride Other: Laboratory Biomarker Analysis Drug: Temozolomide Drug: Vincristine Sulfate Liposome | Phase 2 |
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| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 175 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody NSC # 742460]) in Combination With Intensive Multi-agent Interval Compressed Therapy for Patients With High-Risk Rhabdomyosarcoma |
| Study Start Date : | January 2010 |
| Actual Primary Completion Date : | June 2016 |
| Actual Study Completion Date : | June 2016 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Temozolomide
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group 1 (chemotherapy, radiation therapy, cixutumumab)
Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.
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Biological: Cixutumumab
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Drug: Irinotecan Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Vincristine Sulfate Liposome Given IV
Other Name: Marqibo |
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Experimental: Group 2 (chemotherapy, radiation therapy, temozolomide)
Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
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Drug: Cyclophosphamide
Given IV
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Drug: Irinotecan Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Temozolomide Given PO
Other Names:
Drug: Vincristine Sulfate Liposome Given IV
Other Name: Marqibo |
Primary Outcome Measures :
- Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment [ Time Frame: From start to week 26 of therapy ]Proportion of no Grade 3+ cardiac toxicity.
- Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment [ Time Frame: From start to week 26 of therapy ]Proportion of no Grade 4+ non-hematologic toxicity.
- Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 54 weeks ]Number of patients with grade 3+ adverse events (AE) during therapy. (Grade 3+) = (Grade 3 + Grade 4 + Grade 5) . Grade 3: Severe and undesirable AE; Grade 4: Life threatening or disabling AE; Grade 5: Death related to AE.
- Event-Free Survival [ Time Frame: 3 years ]Probability of no relapse, secondary malignancy, or death after 3 years in the study.
Secondary Outcome Measures :
- Response Rate (CR + PR) [ Time Frame: From the start of treatment until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities ]Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at > 4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment; Overall Response (OR) = CR + PR.
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| Ages Eligible for Study: | up to 49 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 =< 16 years of age
- No prior chemotherapy or radiotherapy except for use of corticosteroids or emergent radiation therapy; patients requiring emergency radiation are eligible
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Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 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 =< 1.5 x upper limit of normal (ULN) for age, unless there is evidence of biliary obstruction by the tumor
- Shortening fraction >= 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01055314
Locations
Show 139 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Suman Malempati, MD | Children's Oncology Group |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01055314 |
| Other Study ID Numbers: |
NCI-2011-02005 NCI-2011-02005 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) COG-ARST08P1 ARST08P1 ( Other Identifier: Children's Oncology Group ) ARST08P1 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 25, 2010 Key Record Dates |
| Results First Posted: | July 28, 2017 |
| Last Update Posted: | August 29, 2017 |
| Last Verified: | July 2017 |
Additional relevant MeSH terms:
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Sarcoma Rhabdomyosarcoma Rhabdomyosarcoma, Alveolar Rhabdomyosarcoma, Embryonal Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Myosarcoma Neoplasms, Muscle Tissue Dactinomycin Cyclophosphamide Temozolomide Ifosfamide Isophosphamide mustard Doxorubicin |
Liposomal doxorubicin Irinotecan Etoposide Vincristine Etoposide phosphate Podophyllotoxin Camptothecin Antibodies, Monoclonal Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |