Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01055314
• Collaborator: (none)
• Enrollment: 175
• Locations: 139
• Arms: 2
• Duration (Months): 77
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the feasibility of administering IMC-A12 (cixutumumab) in combination with a multi-agent intensive chemotherapy regimen for the treatment of high-risk rhabdomyosarcoma (RMS).

2. To determine the feasibility of adding temozolomide to vincristine (vincristine sulfate)/irinotecan (irinotecan hydrochloride) cycles in patients with high-risk RMS.

3. To assess immediate and short-term side effects of delivery of concurrent temozolomide-vincristine-irinotecan with irradiation in patients with high-risk RMS.

SECONDARY OBJECTIVES:

1. To gain a preliminary estimate of the response rate to IMC-A12 or temozolomide plus vincristine/irinotecan in previously untreated high-risk RMS.

2. To obtain preliminary efficacy data for IMC-A12 or temozolomide in combination with a multi-agent interval compressed chemotherapy regimen in previously untreated high-risk RMS.

3. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F 18 positron emission tomography (FDG PET) and to compare assessment of response using standard imaging techniques with response assessed by FDG PET.

4. To assess changes in serum levels of insulin-like growth factor (IGF)-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.

OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2 treatment groups according to the timing of their enrollment onto the study.

GROUP 1: Patients receive vincristine sulfate intravenously (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.

GROUP 2: 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 orally (PO) on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.

GROUP 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and undergo radiation therapy* as in group 1. Patients also receive temozolomide as in group 2. (Discontinued as of January 2013)

NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those requiring emergency radiotherapy may receive radiation therapy starting in week 1; cixutumumab should be withheld during radiation therapy.

After completion of study therapy, patients are followed up at 3 weeks and then periodically for up to 5 years.

Study Design

• Study Type: Interventional
• 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: Jan 1, 2010
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: Cixutumumab; Given IV; Other Names: Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12 IMC-A12 ; Drug: Cyclophosphamide; Given IV; Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Biological: Dactinomycin; Given IV; Other Names: Actinomycin A IV Actinomycin C1 ACTINOMYCIN D Actinomycin I1 Actinomycin IV Actinomycin X 1 Actinomycin-[thr-val-pro-sar-meval] Cosmegen DACT Dactinomycine Lyovac Cosmegen Meractinomycin ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 ; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942 Asta Z-4942 Cyfos Holoxan Holoxane Ifex IFO IFO-Cell Ifolem Ifomida Ifomide Ifosfamidum Ifoxan IFX Iphosphamid Iphosphamide Iso-Endoxan Isoendoxan Isophosphamide Mitoxana MJF 9325 MJF-9325 Naxamide Seromida Tronoxal Z 4942 Z-4942 ; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 U-101440E ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Vincristine Sulfate Liposome; Given IV; Other Names: Marqibo
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.	Drug: Cyclophosphamide; Given IV; Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Biological: Dactinomycin; Given IV; Other Names: Actinomycin A IV Actinomycin C1 ACTINOMYCIN D Actinomycin I1 Actinomycin IV Actinomycin X 1 Actinomycin-[thr-val-pro-sar-meval] Cosmegen DACT Dactinomycine Lyovac Cosmegen Meractinomycin ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 ; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942 Asta Z-4942 Cyfos Holoxan Holoxane Ifex IFO IFO-Cell Ifolem Ifomida Ifomide Ifosfamidum Ifoxan IFX Iphosphamid Iphosphamide Iso-Endoxan Isoendoxan Isophosphamide Mitoxana MJF 9325 MJF-9325 Naxamide Seromida Tronoxal Z 4942 Z-4942 ; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 U-101440E ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Temozolomide; Given PO; Other Names: CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temodal Temodar ; Drug: Vincristine Sulfate Liposome; Given IV; Other Names: Marqibo

Outcome Measures

Primary Outcome Measures

1. Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment [From start to week 26 of therapy]

   Proportion of no Grade 3+ cardiac toxicity.

2. Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment [From start to week 26 of therapy]

   Proportion of no Grade 4+ non-hematologic toxicity.

3. Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0 [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.

4. Event-Free Survival [3 years]

   Probability of no relapse, secondary malignancy, or death after 3 years in the study.

Secondary Outcome Measures

1. Response Rate (CR + PR) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
3	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
4	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
5	Southern California Permanente Medical Group	Downey	California	United States	90242
6	Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
7	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
8	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
9	Mattel Children's Hospital UCLA	Los Angeles	California	United States	90095
10	Children's Hospital Central California	Madera	California	United States	93636-8762
11	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
12	Kaiser Permanente-Oakland	Oakland	California	United States	94611
13	Childrens Hospital of Orange County	Orange	California	United States	92868
14	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
15	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
16	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
17	Children's Hospital Colorado	Aurora	Colorado	United States	80045
18	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
19	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
20	Yale University	New Haven	Connecticut	United States	06520
21	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
22	MedStar Georgetown University Hospital	Washington, D.C.	District of Columbia	United States	20007
23	Children's National Medical Center	Washington, D.C.	District of Columbia	United States	20010
24	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
25	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
26	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
27	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
28	Nemours Children's Hospital	Orlando	Florida	United States	32827
29	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
30	All Children's Hospital	Saint Petersburg	Florida	United States	33701
31	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
32	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
33	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
34	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
35	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
36	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
37	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
38	Loyola University Medical Center	Maywood	Illinois	United States	60153
39	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61602
40	Southern Illinois University	Springfield	Illinois	United States	62702
41	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
42	Blank Children's Hospital	Des Moines	Iowa	United States	50309
43	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
44	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
45	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
46	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
47	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
48	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
49	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
50	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
51	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
52	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
53	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
54	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
55	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan	United States	49008
56	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
57	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota	United States	55455
58	Mayo Clinic	Rochester	Minnesota	United States	55905
59	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
60	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
61	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
62	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
63	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
64	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
65	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
66	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
67	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
68	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
69	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
70	Overlook Hospital	Summit	New Jersey	United States	07902
71	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
72	University of New Mexico	Albuquerque	New Mexico	United States	87106
73	Albany Medical Center	Albany	New York	United States	12208
74	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
75	New York University Langone Medical Center	New York	New York	United States	10016
76	University of Rochester	Rochester	New York	United States	14642
77	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
78	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
79	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
80	Duke University Medical Center	Durham	North Carolina	United States	27710
81	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
82	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
83	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
84	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
85	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
86	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
87	Dayton Children's Hospital	Dayton	Ohio	United States	45404
88	Mercy Children's Hospital	Toledo	Ohio	United States	43608
89	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
90	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
91	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
92	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
93	Oregon Health and Science University	Portland	Oregon	United States	97239
94	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
95	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
96	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
97	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
98	Rhode Island Hospital	Providence	Rhode Island	United States	02903
99	Medical University of South Carolina	Charleston	South Carolina	United States	29425
100	Palmetto Health Richland	Columbia	South Carolina	United States	29203
101	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
102	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
103	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
104	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
105	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
106	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
107	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
108	Medical City Dallas Hospital	Dallas	Texas	United States	75230
109	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
110	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
111	Baylor College of Medicine	Houston	Texas	United States	77030
112	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
113	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
114	Childrens Hospital-King's Daughters	Norfolk	Virginia	United States	23507
115	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
116	Seattle Children's Hospital	Seattle	Washington	United States	98105
117	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
118	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington	United States	98405
119	West Virginia University Charleston	Charleston	West Virginia	United States	25304
120	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
121	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
122	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
123	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
124	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
125	Royal Children's Hospital-Brisbane	Herston	Queensland	Australia	4029
126	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
127	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
128	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
129	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
130	IWK Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9
131	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
132	Chedoke-McMaster Hospitals	Hamilton	Ontario	Canada	L8S 4L8
133	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
134	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
135	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
136	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
137	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
138	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
139	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Suman Malempati, MD, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01055314
• Other Study ID Numbers: NCI-2011-02005; NCI-2011-02005; COG-ARST08P1; ARST08P1; ARST08P1; U10CA180886; U10CA098543
• First Posted: Jan 25, 2010
• Last Update Posted: Aug 29, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Sarcoma; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; Dactinomycin; Cyclophosphamide; Temozolomide; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Irinotecan; Etoposide; Vincristine; Etoposide phosphate; Podophyllotoxin; Camptothecin; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	The number of participants started is 175. Eight patients were declared ineligible by the study chair, and one patient didn't receive treatment.

Arm/Group Title	IMC-A12	Temozolomide
Arm/Group Description	IMC-A12 + Multi-agent intensive chemotherapy regimen.	Add temozolomide to vincristine/irinotecan cycles.
Period Title: Overall Study
STARTED	100	75
COMPLETED	55	37
NOT COMPLETED	45	38

Baseline Characteristics

Arm/Group Title	IMC-A12	Temozolomide	Total
Arm/Group Description	IMC-A12 + Multi-agent intensive chemotherapy regimen.	Add temozolomide to vincristine/irinotecan cycles.	Total of all reporting groups
Overall Participants	100	75	175
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	161.93 (67.36)	152.04 (79.20)	157.69 (72.62)
Sex: Female, Male (Count of Participants)
Female	53 53%	30 40%	83 47.4%
Male	47 47%	45 60%	92 52.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 17%	18 24%	35 20%
Not Hispanic or Latino	77 77%	55 73.3%	132 75.4%
Unknown or Not Reported	6 6%	2 2.7%	8 4.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 3%	0 0%	3 1.7%
Native Hawaiian or Other Pacific Islander	1 1%	1 1.3%	2 1.1%
Black or African American	12 12%	10 13.3%	22 12.6%
White	74 74%	53 70.7%	127 72.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	10 10%	11 14.7%	21 12%

Outcome Measures

1. Primary Outcome

Title	Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment
Description	Proportion of no Grade 3+ cardiac toxicity.
Time Frame	From start to week 26 of therapy

Outcome Measure Data

Analysis Population Description

18 participants were excluded because of ineligibility or insufficient information to assess feasibility.

Arm/Group Title	IMC-A12
Arm/Group Description	IMC-A12 + Multi-agent intensive chemotherapy regimen.
Measure Participants	82
Number (95% Confidence Interval) [Proportion of Participants]	0.9390 0.9%

2. Primary Outcome

Title	Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment
Description	Proportion of no Grade 4+ non-hematologic toxicity.
Time Frame	From start to week 26 of therapy

Outcome Measure Data

Analysis Population Description

13 participants were excluded because of ineligibility or insufficient information to assess feasibility.

Arm/Group Title	Temozolomide
Arm/Group Description	Add temozolomide to vincristine/irinotecan cycles.
Measure Participants	62
Number (95% Confidence Interval) [Proportion of Participants]	0.7097 0.7%

3. Primary Outcome

Title	Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Description	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.
Time Frame	Up to 54 weeks

Outcome Measure Data

Analysis Population Description

9 participants who were ineligible or did not receive treatment were excluded.

Arm/Group Title	IMC-A12	Temozolomide
Arm/Group Description	IMC-A12 + Multi-agent intensive chemotherapy regimen.	Add temozolomide to vincristine/irinotecan cycles.
Measure Participants	96	70
Number [Participants]	89 89%	61 81.3%

4. Primary Outcome

Title	Event-Free Survival
Description	Probability of no relapse, secondary malignancy, or death after 3 years in the study.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

9 participants who were ineligible or did not receive treatment were excluded.

Arm/Group Title	IMC-A12	Temozolomide
Arm/Group Description	IMC-A12 + Multi-agent intensive chemotherapy regimen.	Add temozolomide to vincristine/irinotecan cycles.
Measure Participants	96	70
Number (95% Confidence Interval) [Probability]	0.1627	0.1919

5. Secondary Outcome

Title	Response Rate (CR + PR)
Description	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.
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

Outcome Measure Data

Analysis Population Description

20 participants were excluded because of ineligibility or absence in overall response evaluation.

Arm/Group Title	IMC-A12	Temozolomide
Arm/Group Description	IMC-A12 + Multi-agent intensive chemotherapy regimen.	Add temozolomide to vincristine/irinotecan cycles.
Measure Participants	90	65
Number (95% Confidence Interval) [Proportion of Participants]	0.7667 0.8%	0.7846 1%

Adverse Events

Adverse Event Reporting Description	SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Nine participants who were ineligible or did not receive treatment were excluded (both serious and other).
Arm/Group Title	Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)		Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)
Arm/Group Description	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 & 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47 & 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, & 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28 & 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41 & 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41 & 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. Cixutumumab: Given IV Cyclophosphamide: Given IV Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Vincristine Sulfate		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. Cyclophosphamide: Given IV Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Temozolomide: Given PO Vincristine Sulfate Liposome: Given IV
All Cause Mortality
	Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)		Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)		Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/96 (82.3%)		40/70 (57.1%)
Blood and lymphatic system disorders
Anemia	4/96 (4.2%)	5	1/70 (1.4%)	1
Bone marrow hypocellular	1/96 (1%)	1	0/70 (0%)	0
Disseminated intravascular coagulation	1/96 (1%)	1	0/70 (0%)	0
Febrile neutropenia	7/96 (7.3%)	12	0/70 (0%)	0
Cardiac disorders
Cardiac arrest	0/96 (0%)	0	1/70 (1.4%)	1
Heart failure	1/96 (1%)	1	0/70 (0%)	0
Left ventricular systolic dysfunction	2/96 (2.1%)	2	1/70 (1.4%)	1
Sinus tachycardia	2/96 (2.1%)	2	0/70 (0%)	0
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Endocrine disorders
Endocrine disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Gastrointestinal disorders
Abdominal distension	1/96 (1%)	1	0/70 (0%)	0
Abdominal pain	5/96 (5.2%)	7	0/70 (0%)	0
Anal ulcer	1/96 (1%)	1	0/70 (0%)	0
Ascites	1/96 (1%)	1	0/70 (0%)	0
Colitis	5/96 (5.2%)	5	0/70 (0%)	0
Diarrhea	8/96 (8.3%)	8	1/70 (1.4%)	1
Esophageal pain	1/96 (1%)	1	0/70 (0%)	0
Esophageal stenosis	1/96 (1%)	1	0/70 (0%)	0
Esophagitis	1/96 (1%)	1	0/70 (0%)	0
Gastric hemorrhage	1/96 (1%)	1	0/70 (0%)	0
Ileus	1/96 (1%)	1	0/70 (0%)	0
Mucositis oral	7/96 (7.3%)	10	0/70 (0%)	0
Nausea	4/96 (4.2%)	5	0/70 (0%)	0
Oral hemorrhage	1/96 (1%)	1	0/70 (0%)	0
Oral pain	1/96 (1%)	2	0/70 (0%)	0
Pancreatitis	2/96 (2.1%)	2	0/70 (0%)	0
Rectal fistula	1/96 (1%)	1	0/70 (0%)	0
Rectal hemorrhage	2/96 (2.1%)	2	0/70 (0%)	0
Rectal pain	1/96 (1%)	1	0/70 (0%)	0
Typhlitis	5/96 (5.2%)	5	0/70 (0%)	0
Upper gastrointestinal hemorrhage	2/96 (2.1%)	2	0/70 (0%)	0
Vomiting	5/96 (5.2%)	5	0/70 (0%)	0
General disorders
Death NOS	30/96 (31.3%)	30	30/70 (42.9%)	30
Fever	1/96 (1%)	2	0/70 (0%)	0
Multi-organ failure	1/96 (1%)	1	0/70 (0%)	0
Pain	2/96 (2.1%)	2	0/70 (0%)	0
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Portal hypertension	2/96 (2.1%)	2	0/70 (0%)	0
Immune system disorders
Allergic reaction	2/96 (2.1%)	2	0/70 (0%)	0
Infections and infestations
Appendicitis	1/96 (1%)	1	0/70 (0%)	0
Catheter related infection	2/96 (2.1%)	2	0/70 (0%)	0
Enterocolitis infectious	1/96 (1%)	1	0/70 (0%)	0
Esophageal infection	1/96 (1%)	1	0/70 (0%)	0
Gum infection	1/96 (1%)	1	0/70 (0%)	0
Infections and infestations - Other, specify	4/96 (4.2%)	6	1/70 (1.4%)	1
Lung infection	2/96 (2.1%)	3	0/70 (0%)	0
Mucosal infection	0/96 (0%)	0	1/70 (1.4%)	1
Sepsis	8/96 (8.3%)	9	0/70 (0%)	0
Sinusitis	1/96 (1%)	1	0/70 (0%)	0
Skin infection	4/96 (4.2%)	8	0/70 (0%)	0
Stoma site infection	1/96 (1%)	1	0/70 (0%)	0
Tracheitis	1/96 (1%)	1	0/70 (0%)	0
Injury, poisoning and procedural complications
Dermatitis radiation	1/96 (1%)	1	0/70 (0%)	0
Fracture	1/96 (1%)	1	0/70 (0%)	0
Investigations
Alanine aminotransferase increased	9/96 (9.4%)	10	0/70 (0%)	0
Alkaline phosphatase increased	1/96 (1%)	1	0/70 (0%)	0
Aspartate aminotransferase increased	5/96 (5.2%)	5	0/70 (0%)	0
Blood bilirubin increased	3/96 (3.1%)	3	0/70 (0%)	0
Ejection fraction decreased	1/96 (1%)	1	0/70 (0%)	0
GGT increased	3/96 (3.1%)	4	0/70 (0%)	0
INR increased	1/96 (1%)	1	0/70 (0%)	0
Lipase increased	3/96 (3.1%)	4	0/70 (0%)	0
Lymphocyte count decreased	2/96 (2.1%)	4	0/70 (0%)	0
Neutrophil count decreased	5/96 (5.2%)	9	1/70 (1.4%)	1
Platelet count decreased	8/96 (8.3%)	14	0/70 (0%)	0
Serum amylase increased	1/96 (1%)	2	0/70 (0%)	0
Weight loss	6/96 (6.3%)	6	1/70 (1.4%)	1
White blood cell decreased	5/96 (5.2%)	10	0/70 (0%)	0
Metabolism and nutrition disorders
Anorexia	4/96 (4.2%)	4	1/70 (1.4%)	1
Dehydration	7/96 (7.3%)	7	0/70 (0%)	0
Hypercalcemia	1/96 (1%)	1	0/70 (0%)	0
Hyperglycemia	10/96 (10.4%)	10	0/70 (0%)	0
Hypertriglyceridemia	1/96 (1%)	1	0/70 (0%)	0
Hypoalbuminemia	1/96 (1%)	1	0/70 (0%)	0
Hypocalcemia	1/96 (1%)	1	0/70 (0%)	0
Hypokalemia	5/96 (5.2%)	5	0/70 (0%)	0
Hyponatremia	3/96 (3.1%)	4	0/70 (0%)	0
Hypophosphatemia	3/96 (3.1%)	3	0/70 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Pain in extremity	1/96 (1%)	1	0/70 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	1/96 (1%)	1	0/70 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	7/96 (7.3%)	7	5/70 (7.1%)	5
Nervous system disorders
Depressed level of consciousness	2/96 (2.1%)	2	0/70 (0%)	0
Hydrocephalus	1/96 (1%)	1	0/70 (0%)	0
Peripheral sensory neuropathy	2/96 (2.1%)	2	0/70 (0%)	0
Seizure	0/96 (0%)	0	1/70 (1.4%)	1
Syncope	3/96 (3.1%)	3	0/70 (0%)	0
Vasovagal reaction	1/96 (1%)	1	0/70 (0%)	0
Psychiatric disorders
Delirium	1/96 (1%)	1	0/70 (0%)	0
Renal and urinary disorders
Acute kidney injury	2/96 (2.1%)	2	0/70 (0%)	0
Hematuria	2/96 (2.1%)	2	0/70 (0%)	0
Reproductive system and breast disorders
Penile pain	1/96 (1%)	1	0/70 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/96 (0%)	0	1/70 (1.4%)	1
Apnea	2/96 (2.1%)	2	0/70 (0%)	0
Epistaxis	1/96 (1%)	2	0/70 (0%)	0
Hypoxia	1/96 (1%)	3	0/70 (0%)	0
Laryngeal edema	1/96 (1%)	1	0/70 (0%)	0
Pulmonary edema	1/96 (1%)	1	0/70 (0%)	0
Respiratory failure	1/96 (1%)	1	1/70 (1.4%)	1
Sore throat	1/96 (1%)	1	0/70 (0%)	0
Stridor	2/96 (2.1%)	2	0/70 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/96 (1%)	1	0/70 (0%)	0
Vascular disorders
Hypotension	6/96 (6.3%)	7	0/70 (0%)	0
Thromboembolic event	2/96 (2.1%)	2	0/70 (0%)	0
Vascular disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)		Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/96 (88.5%)		63/70 (90%)
Blood and lymphatic system disorders
Anemia	9/96 (9.4%)	11	4/70 (5.7%)	4
Blood and lymphatic system disorders - Other, specify	0/96 (0%)	0	1/70 (1.4%)	1
Disseminated intravascular coagulation	0/96 (0%)	0	2/70 (2.9%)	3
Febrile neutropenia	35/96 (36.5%)	58	33/70 (47.1%)	56
Cardiac disorders
Left ventricular systolic dysfunction	0/96 (0%)	0	1/70 (1.4%)	1
Sinus tachycardia	3/96 (3.1%)	3	1/70 (1.4%)	1
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Eye disorders
Blurred vision	0/96 (0%)	0	1/70 (1.4%)	1
Eye disorders - Other, specify	1/96 (1%)	1	1/70 (1.4%)	1
Gastrointestinal disorders
Abdominal distension	2/96 (2.1%)	2	1/70 (1.4%)	1
Abdominal pain	7/96 (7.3%)	8	8/70 (11.4%)	10
Anal fistula	1/96 (1%)	1	2/70 (2.9%)	2
Anal hemorrhage	1/96 (1%)	1	0/70 (0%)	0
Anal mucositis	1/96 (1%)	1	0/70 (0%)	0
Anal pain	0/96 (0%)	0	3/70 (4.3%)	3
Ascites	1/96 (1%)	1	2/70 (2.9%)	2
Colitis	7/96 (7.3%)	10	9/70 (12.9%)	10
Constipation	9/96 (9.4%)	10	4/70 (5.7%)	4
Diarrhea	29/96 (30.2%)	32	12/70 (17.1%)	16
Duodenal obstruction	0/96 (0%)	0	1/70 (1.4%)	1
Enterocolitis	4/96 (4.2%)	4	2/70 (2.9%)	2
Esophageal pain	1/96 (1%)	1	0/70 (0%)	0
Esophagitis	1/96 (1%)	1	0/70 (0%)	0
Gastric ulcer	1/96 (1%)	1	0/70 (0%)	0
Gastritis	0/96 (0%)	0	1/70 (1.4%)	1
Gastrointestinal disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Gastroparesis	0/96 (0%)	0	1/70 (1.4%)	1
Ileus	1/96 (1%)	1	0/70 (0%)	0
Mucositis oral	9/96 (9.4%)	13	14/70 (20%)	17
Nausea	12/96 (12.5%)	13	7/70 (10%)	8
Obstruction gastric	0/96 (0%)	0	1/70 (1.4%)	1
Oral pain	0/96 (0%)	0	1/70 (1.4%)	1
Pancreatitis	1/96 (1%)	1	3/70 (4.3%)	3
Proctitis	2/96 (2.1%)	2	0/70 (0%)	0
Rectal pain	0/96 (0%)	0	3/70 (4.3%)	3
Salivary duct inflammation	1/96 (1%)	1	0/70 (0%)	0
Typhlitis	2/96 (2.1%)	2	6/70 (8.6%)	6
Upper gastrointestinal hemorrhage	1/96 (1%)	1	0/70 (0%)	0
Vomiting	9/96 (9.4%)	11	9/70 (12.9%)	10
General disorders
Edema limbs	3/96 (3.1%)	3	2/70 (2.9%)	2
Facial pain	0/96 (0%)	0	1/70 (1.4%)	1
Fatigue	1/96 (1%)	1	2/70 (2.9%)	2
Fever	6/96 (6.3%)	6	3/70 (4.3%)	3
Gait disturbance	1/96 (1%)	1	1/70 (1.4%)	1
Irritability	1/96 (1%)	1	1/70 (1.4%)	1
Pain	21/96 (21.9%)	22	7/70 (10%)	7
Immune system disorders
Allergic reaction	1/96 (1%)	1	1/70 (1.4%)	1
Anaphylaxis	1/96 (1%)	1	0/70 (0%)	0
Infections and infestations
Abdominal infection	1/96 (1%)	1	1/70 (1.4%)	1
Bronchial infection	0/96 (0%)	0	1/70 (1.4%)	1
Catheter related infection	7/96 (7.3%)	8	2/70 (2.9%)	3
Device related infection	1/96 (1%)	1	0/70 (0%)	0
Enterocolitis infectious	2/96 (2.1%)	2	1/70 (1.4%)	1
Infections and infestations - Other, specify	15/96 (15.6%)	23	17/70 (24.3%)	22
Lung infection	1/96 (1%)	1	2/70 (2.9%)	2
Mucosal infection	0/96 (0%)	0	1/70 (1.4%)	1
Nail infection	1/96 (1%)	2	2/70 (2.9%)	2
Pharyngitis	1/96 (1%)	1	0/70 (0%)	0
Sepsis	3/96 (3.1%)	3	6/70 (8.6%)	6
Sinusitis	1/96 (1%)	1	1/70 (1.4%)	1
Skin infection	2/96 (2.1%)	3	4/70 (5.7%)	4
Small intestine infection	1/96 (1%)	1	1/70 (1.4%)	1
Soft tissue infection	1/96 (1%)	2	0/70 (0%)	0
Stoma site infection	2/96 (2.1%)	2	0/70 (0%)	0
Tooth infection	1/96 (1%)	1	0/70 (0%)	0
Upper respiratory infection	1/96 (1%)	1	0/70 (0%)	0
Urinary tract infection	5/96 (5.2%)	5	7/70 (10%)	9
Vulval infection	2/96 (2.1%)	2	0/70 (0%)	0
Wound infection	3/96 (3.1%)	3	0/70 (0%)	0
Injury, poisoning and procedural complications
Dermatitis radiation	3/96 (3.1%)	3	5/70 (7.1%)	5
Fall	1/96 (1%)	1	0/70 (0%)	0
Postoperative hemorrhage	1/96 (1%)	1	0/70 (0%)	0
Spinal fracture	1/96 (1%)	1	0/70 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/96 (0%)	0	1/70 (1.4%)	1
Alanine aminotransferase increased	15/96 (15.6%)	22	15/70 (21.4%)	22
Alkaline phosphatase increased	0/96 (0%)	0	1/70 (1.4%)	2
Aspartate aminotransferase increased	9/96 (9.4%)	12	11/70 (15.7%)	14
Blood bilirubin increased	2/96 (2.1%)	2	1/70 (1.4%)	1
CPK increased	1/96 (1%)	1	0/70 (0%)	0
Creatinine increased	2/96 (2.1%)	2	1/70 (1.4%)	1
Fibrinogen decreased	0/96 (0%)	0	2/70 (2.9%)	2
GGT increased	6/96 (6.3%)	9	1/70 (1.4%)	2
Investigations - Other, specify	2/96 (2.1%)	2	1/70 (1.4%)	1
Lipase increased	4/96 (4.2%)	4	4/70 (5.7%)	4
Lymphocyte count decreased	3/96 (3.1%)	5	1/70 (1.4%)	1
Neutrophil count decreased	4/96 (4.2%)	4	4/70 (5.7%)	4
Platelet count decreased	8/96 (8.3%)	10	6/70 (8.6%)	7
Serum amylase increased	4/96 (4.2%)	5	2/70 (2.9%)	2
Weight loss	10/96 (10.4%)	13	2/70 (2.9%)	2
White blood cell decreased	6/96 (6.3%)	6	3/70 (4.3%)	5
Metabolism and nutrition disorders
Acidosis	1/96 (1%)	3	2/70 (2.9%)	3
Alkalosis	0/96 (0%)	0	1/70 (1.4%)	2
Anorexia	15/96 (15.6%)	18	12/70 (17.1%)	14
Dehydration	9/96 (9.4%)	9	3/70 (4.3%)	5
Hypercalcemia	3/96 (3.1%)	3	1/70 (1.4%)	1
Hyperglycemia	20/96 (20.8%)	25	6/70 (8.6%)	7
Hyperkalemia	2/96 (2.1%)	2	2/70 (2.9%)	2
Hypermagnesemia	0/96 (0%)	0	1/70 (1.4%)	1
Hypernatremia	1/96 (1%)	1	1/70 (1.4%)	1
Hypertriglyceridemia	1/96 (1%)	1	1/70 (1.4%)	1
Hyperuricemia	0/96 (0%)	0	2/70 (2.9%)	2
Hypoalbuminemia	6/96 (6.3%)	7	2/70 (2.9%)	3
Hypocalcemia	6/96 (6.3%)	7	5/70 (7.1%)	8
Hypoglycemia	1/96 (1%)	1	0/70 (0%)	0
Hypokalemia	13/96 (13.5%)	18	13/70 (18.6%)	17
Hypomagnesemia	1/96 (1%)	1	1/70 (1.4%)	1
Hyponatremia	11/96 (11.5%)	13	9/70 (12.9%)	11
Hypophosphatemia	9/96 (9.4%)	12	6/70 (8.6%)	8
Metabolism and nutrition disorders - Other, specify	0/96 (0%)	0	2/70 (2.9%)	2
Tumor lysis syndrome	1/96 (1%)	1	1/70 (1.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/96 (2.1%)	2	5/70 (7.1%)	7
Bone pain	3/96 (3.1%)	4	2/70 (2.9%)	2
Chest wall pain	1/96 (1%)	1	0/70 (0%)	0
Generalized muscle weakness	1/96 (1%)	1	0/70 (0%)	0
Joint range of motion decreased cervical spine	1/96 (1%)	1	0/70 (0%)	0
Kyphosis	1/96 (1%)	1	0/70 (0%)	0
Muscle weakness lower limb	2/96 (2.1%)	2	0/70 (0%)	0
Musculoskeletal and connective tissue disorder - Other, specify	2/96 (2.1%)	2	0/70 (0%)	0
Myositis	1/96 (1%)	1	0/70 (0%)	0
Pain in extremity	2/96 (2.1%)	2	3/70 (4.3%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	2/96 (2.1%)	2	1/70 (1.4%)	2
Nervous system disorders
Depressed level of consciousness	0/96 (0%)	0	1/70 (1.4%)	1
Dizziness	1/96 (1%)	1	0/70 (0%)	0
Encephalopathy	1/96 (1%)	1	1/70 (1.4%)	1
Facial nerve disorder	0/96 (0%)	0	1/70 (1.4%)	1
Headache	1/96 (1%)	1	4/70 (5.7%)	6
Lethargy	1/96 (1%)	1	1/70 (1.4%)	1
Nervous system disorders - Other, specify	0/96 (0%)	0	2/70 (2.9%)	2
Neuralgia	0/96 (0%)	0	2/70 (2.9%)	2
Peripheral motor neuropathy	4/96 (4.2%)	5	6/70 (8.6%)	6
Peripheral sensory neuropathy	2/96 (2.1%)	3	2/70 (2.9%)	3
Pyramidal tract syndrome	1/96 (1%)	1	0/70 (0%)	0
Recurrent laryngeal nerve palsy	0/96 (0%)	0	1/70 (1.4%)	1
Reversible posterior leukoencephalopathy syndrome	0/96 (0%)	0	1/70 (1.4%)	1
Seizure	1/96 (1%)	1	3/70 (4.3%)	3
Somnolence	0/96 (0%)	0	2/70 (2.9%)	2
Syncope	2/96 (2.1%)	3	2/70 (2.9%)	2
Psychiatric disorders
Agitation	0/96 (0%)	0	2/70 (2.9%)	2
Anxiety	5/96 (5.2%)	5	2/70 (2.9%)	2
Confusion	1/96 (1%)	1	1/70 (1.4%)	1
Depression	1/96 (1%)	1	0/70 (0%)	0
Insomnia	1/96 (1%)	1	0/70 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/96 (1%)	1	1/70 (1.4%)	1
Bladder spasm	1/96 (1%)	1	0/70 (0%)	0
Hematuria	3/96 (3.1%)	3	1/70 (1.4%)	1
Renal and urinary disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Urinary retention	6/96 (6.3%)	6	2/70 (2.9%)	2
Urinary tract obstruction	4/96 (4.2%)	5	3/70 (4.3%)	3
Urinary tract pain	0/96 (0%)	0	1/70 (1.4%)	1
Reproductive system and breast disorders
Irregular menstruation	1/96 (1%)	1	0/70 (0%)	0
Menorrhagia	1/96 (1%)	2	0/70 (0%)	0
Pelvic pain	1/96 (1%)	1	0/70 (0%)	0
Penile pain	1/96 (1%)	2	0/70 (0%)	0
Vaginal hemorrhage	0/96 (0%)	0	1/70 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/96 (3.1%)	3	3/70 (4.3%)	3
Epistaxis	4/96 (4.2%)	5	1/70 (1.4%)	2
Hoarseness	1/96 (1%)	1	0/70 (0%)	0
Hypoxia	1/96 (1%)	1	2/70 (2.9%)	2
Laryngeal mucositis	1/96 (1%)	1	0/70 (0%)	0
Nasal congestion	0/96 (0%)	0	1/70 (1.4%)	1
Pleural effusion	4/96 (4.2%)	5	3/70 (4.3%)	3
Pleuritic pain	1/96 (1%)	1	0/70 (0%)	0
Pneumonitis	1/96 (1%)	1	1/70 (1.4%)	1
Pneumothorax	1/96 (1%)	1	0/70 (0%)	0
Pulmonary edema	0/96 (0%)	0	3/70 (4.3%)	3
Respiratory failure	0/96 (0%)	0	3/70 (4.3%)	3
Respiratory, thoracic and mediastinal disorders - Other, specify	1/96 (1%)	1	0/70 (0%)	0
Skin and subcutaneous tissue disorders
Pain of skin	1/96 (1%)	1	1/70 (1.4%)	1
Palmar-plantar erythrodysesthesia syndrome	0/96 (0%)	0	1/70 (1.4%)	1
Pruritus	1/96 (1%)	1	0/70 (0%)	0
Rash maculo-papular	0/96 (0%)	0	4/70 (5.7%)	4
Skin and subcutaneous tissue disorders - Other, specify	1/96 (1%)	1	1/70 (1.4%)	1
Skin ulceration	2/96 (2.1%)	3	0/70 (0%)	0
Urticaria	2/96 (2.1%)	2	0/70 (0%)	0
Vascular disorders
Hypertension	3/96 (3.1%)	4	2/70 (2.9%)	2
Hypotension	5/96 (5.2%)	6	3/70 (4.3%)	3
Lymphedema	0/96 (0%)	0	1/70 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.