Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01946529
• Collaborator: University of Tennessee Health Science Center (Other), University of Florida (Other), Nemours Children's Clinic (Other)
• Enrollment: 24
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 150.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This protocol will study treatment for Ewing sarcoma family of tumors (ESFT) and desmoplastic small round cell tumor (DSRCT). Participants with ESFT will be divided into two treatment groups, A or B, based on tumor characteristics.

Group A (standard risk) participants have tumor that is not in the pelvis, has not spread to other parts of the body, and are less than 14 years of age. Because previous clinical trials have shown that standard treatment is very effective for children whose tumors have these characteristics, these participants will receive standard treatment.

Group B (high risk) participants are 14 years of age or older or have tumor in the pelvis, or the tumor has spread to other parts of the body. Participants with DSRCT in the abdomen and/or pelvis or with tumor that cannot be removed by surgery alone or has spread to other parts of the body will be included in Group B. Participants in this group are considered high risk because there is a greater chance of tumor recurring following standard treatments currently in use.

All participants will be followed and evaluated for 10 years following completion of therapy.

Condition or Disease	Intervention/Treatment	Phase
Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor	Drug: vincristine; Drug: doxorubicin; Drug: cyclophosphamide; Drug: ifosfamide; Drug: etoposide; Drug: temozolomide; Drug: temsirolimus; Drug: bevacizumab; Drug: sorafenib; Procedure: surgery; Radiation: radiation	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

• To estimate the response rate to two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high-risk Ewing sarcoma family of tumors (ESFT).

SECONDARY OBJECTIVES:

• To estimate the overall survival and progression-free survival in participants with ESFT treated with these approaches.

• To estimate the time to progression in participants with ESFT treated in Group B (high risk).

• To estimate the cumulative incidence of local failure following local control paradigm in this trial.

Group A:

Participants will receive interval compressed (every 2 weeks) alternating courses of chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VDC) and with ifosfamide and etoposide (IE). Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.

Group B:

Participants eligible for the window therapy will receive two courses (21 days duration each) of mTOR inhibitor, temsirolimus, in combination with temozolomide and irinotecan. Irinotecan (20 mg/m^{2) will be administered IV on a protracted schedule of daily for 5 days, 2 days off, repeated daily x 5 [(qdx5)x2], temozolomide (100 mg/m}2) PO daily x 5 days and temsirolimus 35 mg/m^{2 IV weekly on day 1 and 8. Following window treatment (weeks 1 - 6), participants will proceed to induction chemotherapy (weeks 7 - 33) consisting of interval compressed (every 2 weeks) alternating courses of chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VDC) with ifosfamide and etoposide (IE). Doxorubicin will be omitted following a total cumulative dose of 375 mg/m}2. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of induction chemotherapy (week 19). Participants whose tumors respond to window therapy will receive temsirolimus, temozolomide and irinotecan at weeks 29 and 31 in place of ifosfamide and etoposide. Following induction therapy, participants will receive six 21-day courses of maintenance therapy consisting of bevacizumab IV on day 1 and daily oral sorafenib and low-dose cyclophosphamide day 1 through day 21.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors
• Actual Study Start Date: Dec 27, 2013
• Actual Primary Completion Date: Aug 1, 2015
• Anticipated Study Completion Date: Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A (Standard Risk) Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone, or surgery followed by radiation. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.	Drug: vincristine; Dosage and route of administration: Infants < 12 months of age: 0.05 mg/kg IV day 1; participants ≥ 12 months of age: 1.5 mg/m^2 IV day 1 (max. dose 2 mg).; Other Names: Oncovin(R) ; Drug: doxorubicin; Dosage and route of administration: Infants < 1 year 2.5 mg/kg continuous infusion (CI) over 48 hours, days 1-2; participants > 1 year of age 75 mg/m^2 CI over 48 hours, days 1-2.; Other Names: Adriamycin(R) ; Drug: cyclophosphamide; Dosage and route of administration: The dose and route are different in neo-adjuvant/adjuvant chemotherapy and maintenance therapy. Please see the Detailed Description for further information.; Other Names: Cytoxan(R) ; Drug: ifosfamide; Dosage and route of administration: Infants < 1 year of age 60 mg/kg/day IV over 60 minutes days 1-5; participants > 12 months of age 1800 mg/m^2 IV over 60 minutes x 5 days, days 1-5.; Other Names: Ifex(R) ; Drug: etoposide; Dosage and route of administration: Infants < 1 year of age 3.3 mg/kg/day IV over 60 minutes days 1-5; children > 1 year 100 mg/m^2 daily IV over 60 minutes days 1-5.; Other Names: VP-16 Vepesid(R) ; Procedure: surgery; If participant meets the criteria, they will have surgical resection of their tumor.; Other Names: therapeutic conventional surgery ; Radiation: radiation; If the participant meets the criteria, participants will receive radiation therapy. Chemotherapy will continue during radiation.; Other Names: proton beam radiation therapy external beam radiation therapy brachytherapy
Active Comparator: Group B (High Risk) Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, irinotecan, temozolomide, temsirolimus, bevacizumab, and sorafenib. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone or surgery followed by radiation.	Drug: doxorubicin; Dosage and route of administration: Infants < 1 year 2.5 mg/kg continuous infusion (CI) over 48 hours, days 1-2; participants > 1 year of age 75 mg/m^2 CI over 48 hours, days 1-2.; Other Names: Adriamycin(R) ; Drug: cyclophosphamide; Dosage and route of administration: The dose and route are different in neo-adjuvant/adjuvant chemotherapy and maintenance therapy. Please see the Detailed Description for further information.; Other Names: Cytoxan(R) ; Drug: ifosfamide; Dosage and route of administration: Infants < 1 year of age 60 mg/kg/day IV over 60 minutes days 1-5; participants > 12 months of age 1800 mg/m^2 IV over 60 minutes x 5 days, days 1-5.; Other Names: Ifex(R) ; Drug: etoposide; Dosage and route of administration: Infants < 1 year of age 3.3 mg/kg/day IV over 60 minutes days 1-5; children > 1 year 100 mg/m^2 daily IV over 60 minutes days 1-5.; Other Names: VP-16 Vepesid(R) ; Drug: temozolomide; Dosage and route of administration: Temozolomide 100 mg/m^2 PO once daily, days 1-5.; Other Names: Temodar(R) ; Drug: temsirolimus; Dosage and route of administration: Temsirolimus 35 mg/m^2 IV once day 1 and day 8.; Other Names: CCI-779 Torisel^TM ; Drug: bevacizumab; Dosage and route of administration: Bevacizumab 15 mg/kg IV on day 1 every 3 weeks.; Other Names: rhumab VEGF Avastin(R) ; Drug: sorafenib; Dosage and route of administration: 90 mg/m^2/dose PO BID; Other Names: BAY-43-9006 Nexavar(R) ; Procedure: surgery; If participant meets the criteria, they will have surgical resection of their tumor.; Other Names: therapeutic conventional surgery ; Radiation: radiation; If the participant meets the criteria, participants will receive radiation therapy. Chemotherapy will continue during radiation.; Other Names: proton beam radiation therapy external beam radiation therapy brachytherapy

Outcome Measures

Primary Outcome Measures

1. Response to Window Therapy (2 Courses) for Group B (High-risk) - ESFT Participants [at 6 weeks after start of therapy (after 2 initial courses)]

   Response rate will be defined as the proportion of patients who achieved complete response or partial response (CR+PR) using the World Health Organization (WHO) criteria evaluated after two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high risk Ewing Sarcoma Family of Tumor (ESFT). Participants who are treated in Group B with Desmoplastic Small Round Cell Tumor (DSRCT) or those who do not receive window therapy will not be included in this analysis.

Secondary Outcome Measures

1. Overall Survival [Maximum of 11 years after the start of therapy]

   Overall survival (OS) is defined as the time interval from the date on study to the date of death or the date of last follow-up. OS will be estimated using the method of Kaplan-Meier for group A and B participants, respectively.

2. Progression-free Survival [Maximum of 11 years after the start of therapy]

   Progression free survival (PFS) is defined as the time interval from the date on study to the date of disease progression or death or the date if last follow-up. PFS will be estimated using the method of Kaplan-Meier for group A and B participants, respectively.

3. Time to Progression [Maximum of 11 years after the start of therapy]

   Median time to progression of group B patients will be estimated from the Kaplan-Meier curve.

4. Local Failure Rate [Maximum of 11 years after the start of therapy]

   Loco-regional failure is defined as the time interval from date of start of local therapy to date of loco-regional failure. Distant failure or death prior to loco-regional failure will be considered competing events in the analyses. The cumulative incidence of loco-regional failure will be estimated using methods described in Kalbfleisch and Prentice.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Group A participants must be <14 years of age at time of diagnosis of histologically proven non-pelvic localized Ewing sarcoma family of tumor (ESFT) involving the bone or soft tissue.

• Group B participants must have newly diagnosed of histologically proven ESFT involving the bone or soft tissue and at least one of the following: metastatic disease (must be biopsy proven), or pelvic primary, or ≥14 years of age at the time of diagnosis.

• OR Group B participants must be newly diagnosed with intra-abdominal, unresectable or metastatic desmoplastic small round cell tumor. Metastatic site must be biopsy proven.

• Age must be ≤25 years.

• Adequate bone marrow function defined as a peripheral absolute neutrophil count (ANC) ≥750/m^{3 and platelet count ≥75,000/m}3 (no transfusion within 7 days of study enrollment). Patients with Ewing sarcoma metastatic to the bone marrow are not required to meet bone marrow criteria for study eligibility and are not evaluable for hematologic toxicity.

• Must have adequate renal function based on age.

• Must not have had prior chemotherapy or radiation therapy. Emergent radiotherapy to preserve vital organ function is permitted. Participants who receive emergent radiation will not be eligible for window therapy.

• Must have adequate hepatic function defined as total bilirubin ≤3.0 mg/dL.

• Must have adequate cardiac function defined as shortening fraction ≥28%.

• Females of childbearing potential and males able to father a child must be willing to practice acceptable methods of birth control to prevent pregnancy.

• Additional criteria for Group B participants who will receive upfront window therapy (does not apply to participants who opt out of window therapy):

• Cytochrome P450 CYP3A4 active agents: Must not be taking any of the following potent CYP3A4 inducers or inhibitors within 1 week prior to study entry: azole antifungals (such as fluconazole, voriconazole, itraconazole, ketoconazole), rifampin, phenytoin, phenobarbitol, carbamazepine, grapefruit juice and St. John's wort.

• Must have measurable disease.

• Must not have received emergent radiation therapy.

• Serum triglyceride level ≤ 300 mg/dL and serum cholesterol ≤ 300 mg/dL.

• Random or fasting glucose within the upper limits of normal for age. If random glucose is elevated, fasting glucose must be within normal range.

• SGOT (AST) and SGPT (ALT) ≤3.0 x upper limit of normal for age.

Exclusion Criteria:

• Participant is pregnant or breastfeeding.

• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

• Participant has a prior history of malignancy, with the exception of non-melanoma skin cancer. Participants with history of skin cancer must have 5 years elapse since that diagnosis, be in remission, and must not have received chemotherapy, immunotherapy, or radiation therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital
• University of Tennessee Health Science Center
• University of Florida
• Nemours Children's Clinic

Investigators

• Principal Investigator: Sara M. Federico, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT01946529
• Other Study ID Numbers: ESFT13; NCI-2013-01657
• First Posted: Sep 19, 2013
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Desmoplastic Small Round Cell Tumor; Sirolimus; Cyclophosphamide; Temozolomide; Ifosfamide; Bevacizumab; Doxorubicin; Etoposide; Vincristine; Sorafenib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at St. Jude Children's Research Hospital between December 2013 and June 2015.

Arm/Group Title	Group A (Standard Risk)	Group B (High Risk) - ESFT	Group B (High Risk) - DSRCT
Arm/Group Description	Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone, or surgery followed by radiation. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.	Group B participants with a diagnosis of Ewing Sarcoma Family of Tumor (ESFT).	Group B participants with a diagnosis of Desmoplastic Small Round Cell Tumor (DSRCT).
Period Title: End of Window Therapy (2 Courses)
STARTED	1	17	6
COMPLETED	1	16	6
NOT COMPLETED	0	1	0
Period Title: End of Window Therapy (2 Courses)
STARTED	1	16	6
COMPLETED	0	0	0
NOT COMPLETED	1	16	6

Baseline Characteristics

Arm/Group Title	Group A (Standard Risk)	Group B (High Risk) - ESFT	Group B (High Risk) - DSRCT	Total
Arm/Group Description	Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone, or surgery followed by radiation. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.	Group B participants with a diagnosis of Ewing Sarcoma Family of Tumor (ESFT).	Group B participants with a diagnosis of Desmoplastic Small Round Cell Tumor (DSRCT).	Total of all reporting groups
Overall Participants	1	16	6	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.0 (0)	13.0 (5.7)	14.7 (4.1)	13.4 (5.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	9 56.3%	1 16.7%	10 43.5%
Male	1 100%	7 43.8%	5 83.3%	13 56.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 6.3%	0 0%	1 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	2 33.3%	2 8.7%
White	1 100%	14 87.5%	3 50%	18 78.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 6.3%	1 16.7%	2 8.7%
Primary disease site (participants) [Number]
Pelvis	0 0%	6 37.5%	5 83.3%	11 47.8%
Other	1 100%	10 62.5%	1 16.7%	12 52.2%
Disease stage (participants) [Number]
Metastases	0 0%	11 68.8%	5 83.3%	16 69.6%
Local	1 100%	5 31.3%	1 16.7%	7 30.4%

Outcome Measures

1. Primary Outcome

Title	Response to Window Therapy (2 Courses) for Group B (High-risk) - ESFT Participants
Description	Response rate will be defined as the proportion of patients who achieved complete response or partial response (CR+PR) using the World Health Organization (WHO) criteria evaluated after two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high risk Ewing Sarcoma Family of Tumor (ESFT). Participants who are treated in Group B with Desmoplastic Small Round Cell Tumor (DSRCT) or those who do not receive window therapy will not be included in this analysis.
Time Frame	at 6 weeks after start of therapy (after 2 initial courses)

Outcome Measure Data

Analysis Population Description

Of the 17 Group B participants with high-risk ESFT, 12 received window therapy and are considered evaluable for this outcome.

Arm/Group Title	Group B (High Risk) - ESFT
Arm/Group Description	Participants received vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. Patients with measurable disease were eligible to receive irinotecan, temozolomide, and temsirolimus. Additionally, all patients were eligible to receive a maintenance therapy at the end of treatment including bevacizumab and sorafenib. Depending on the size and location of the participant's tumor, they had surgery alone, radiation alone, or surgery followed by radiation.
Measure Participants	12
Partial Response (PR)	3 300%
Stable disease (no response) (NR)	8 800%
Progressive Disease (PD)	1 100%

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) is defined as the time interval from the date on study to the date of death or the date of last follow-up. OS will be estimated using the method of Kaplan-Meier for group A and B participants, respectively.
Time Frame	Maximum of 11 years after the start of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression free survival (PFS) is defined as the time interval from the date on study to the date of disease progression or death or the date if last follow-up. PFS will be estimated using the method of Kaplan-Meier for group A and B participants, respectively.
Time Frame	Maximum of 11 years after the start of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to Progression
Description	Median time to progression of group B patients will be estimated from the Kaplan-Meier curve.
Time Frame	Maximum of 11 years after the start of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Local Failure Rate
Description	Loco-regional failure is defined as the time interval from date of start of local therapy to date of loco-regional failure. Distant failure or death prior to loco-regional failure will be considered competing events in the analyses. The cumulative incidence of loco-regional failure will be estimated using methods described in Kalbfleisch and Prentice.
Time Frame	Maximum of 11 years after the start of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected from the on-study date through 05/03/2016.
Arm/Group Title	Group A (Standard Risk)		Group B (High Risk) - ESFT		Group B (High Risk) - DSRCT		Group B (High Risk) - Total
Arm/Group Description	Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone, or surgery followed by radiation. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.		Group B participants with a diagnosis of Ewing Sarcoma Family of Tumor (ESFT).		Group B participants with a diagnosis of Desmoplastic Small Round Cell Tumor (DSRCT).		All Group B High Risk participants with ESFT or DSRCT. Participants received vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. Patients with measurable disease were eligible to receive irinotecan, temozolomide, and temsirolimus. Additionally, all patients were eligible to receive a maintenance therapy at the end of treatment including bevacizumab and sorafenib. Depending on the size and location of the participant's tumor, they had surgery alone, radiation alone, or surgery followed by radiation.
All Cause Mortality
	Group A (Standard Risk)		Group B (High Risk) - ESFT		Group B (High Risk) - DSRCT		Group B (High Risk) - Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A (Standard Risk)		Group B (High Risk) - ESFT		Group B (High Risk) - DSRCT		Group B (High Risk) - Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/16 (6.3%)		0/6 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Diarrhea	0/1 (0%)	0	1/16 (6.3%)	2	0/6 (0%)	0	1/22 (4.5%)	2
Other (Not Including Serious) Adverse Events
	Group A (Standard Risk)		Group B (High Risk) - ESFT		Group B (High Risk) - DSRCT		Group B (High Risk) - Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		16/16 (100%)		6/6 (100%)		22/22 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	1/1 (100%)	1	9/16 (56.3%)	22	3/6 (50%)	4	12/22 (54.5%)	26
Anemia	1/1 (100%)	3	16/16 (100%)	96	6/6 (100%)	34	22/22 (100%)	130
Cardiac disorders
Sinus tachycardia	1/1 (100%)	1	15/16 (93.8%)	66	6/6 (100%)	21	21/22 (95.5%)	87
Sinus bradycardia	0/1 (0%)	0	11/16 (68.8%)	31	4/6 (66.7%)	10	15/22 (68.2%)	41
Cardiac disorders - Other	0/1 (0%)	0	10/16 (62.5%)	15	2/6 (33.3%)	2	12/22 (54.5%)	17
Pericardial effusion	0/1 (0%)	0	1/16 (6.3%)	1	1/6 (16.7%)	1	2/22 (9.1%)	2
Gastrointestinal disorders
Diarrhea	0/1 (0%)	0	15/16 (93.8%)	130	6/6 (100%)	32	21/22 (95.5%)	162
Vomiting	0/1 (0%)	0	12/16 (75%)	51	5/6 (83.3%)	19	17/22 (77.3%)	70
Mucositis oral	0/1 (0%)	0	10/16 (62.5%)	19	4/6 (66.7%)	10	14/22 (63.6%)	29
Nausea	0/1 (0%)	0	10/16 (62.5%)	35	4/6 (66.7%)	7	14/22 (63.6%)	42
Abdominal pain	0/1 (0%)	0	8/16 (50%)	10	2/6 (33.3%)	4	10/22 (45.5%)	14
Constipation	0/1 (0%)	0	7/16 (43.8%)	8	0/6 (0%)	0	7/22 (31.8%)	8
Colitis	0/1 (0%)	0	5/16 (31.3%)	6	1/6 (16.7%)	1	6/22 (27.3%)	7
Esophagitis	0/1 (0%)	0	1/16 (6.3%)	1	1/6 (16.7%)	1	2/22 (9.1%)	2
Oral pain	0/1 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	2/22 (9.1%)	2
General disorders
Fatigue	0/1 (0%)	0	7/16 (43.8%)	7	3/6 (50%)	4	10/22 (45.5%)	11
Fever	0/1 (0%)	0	7/16 (43.8%)	12	1/6 (16.7%)	3	8/22 (36.4%)	15
Malaise	0/1 (0%)	0	2/16 (12.5%)	2	1/6 (16.7%)	1	3/22 (13.6%)	3
Immune system disorders
Allergic reaction	0/1 (0%)	0	6/16 (37.5%)	6	2/6 (33.3%)	3	8/22 (36.4%)	9
Infections and infestations
Wound infection	1/1 (100%)	1	0/16 (0%)	0	1/6 (16.7%)	1	1/22 (4.5%)	1
Mucosa infection	0/1 (0%)	0	5/16 (31.3%)	6	1/6 (16.7%)	1	6/22 (27.3%)	7
Enterocolitis infectious	0/1 (0%)	0	3/16 (18.8%)	5	0/6 (0%)	0	3/22 (13.6%)	5
Lung infection	0/1 (0%)	0	3/16 (18.8%)	3	0/6 (0%)	0	3/22 (13.6%)	3
Anorectal infection	0/1 (0%)	0	1/16 (6.3%)	1	1/6 (16.7%)	1	2/22 (9.1%)	2
Esophageal infection	0/1 (0%)	0	2/16 (12.5%)	3	0/6 (0%)	0	2/22 (9.1%)	3
Investigations
Lymphocyte count decreased	1/1 (100%)	7	15/16 (93.8%)	215	6/6 (100%)	48	21/22 (95.5%)	263
Neutrophil count decreased	1/1 (100%)	6	15/16 (93.8%)	133	6/6 (100%)	36	21/22 (95.5%)	169
White blood cell decreased	1/1 (100%)	4	15/16 (93.8%)	150	6/6 (100%)	36	21/22 (95.5%)	186
Weight loss	0/1 (0%)	0	13/16 (81.3%)	33	5/6 (83.3%)	12	18/22 (81.8%)	45
Platelet count decreased	0/1 (0%)	0	12/16 (75%)	41	5/6 (83.3%)	7	17/22 (77.3%)	48
Alanine aminotransferase increased	0/1 (0%)	0	5/16 (31.3%)	13	2/6 (33.3%)	3	7/22 (31.8%)	16
Aspartate aminotransferase increased	0/1 (0%)	0	4/16 (25%)	8	2/6 (33.3%)	3	6/22 (27.3%)	11
GGT increased	0/1 (0%)	0	2/16 (12.5%)	2	1/6 (16.7%)	1	3/22 (13.6%)	3
Alkaline phosphatase increased	0/1 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	2/22 (9.1%)	2
Blood bilirubin increased	0/1 (0%)	0	1/16 (6.3%)	2	1/6 (16.7%)	1	2/22 (9.1%)	3
Cardiac troponin T increased	0/1 (0%)	0	2/16 (12.5%)	3	0/6 (0%)	0	2/22 (9.1%)	3
Creatinine increased	0/1 (0%)	0	1/16 (6.3%)	1	1/6 (16.7%)	1	2/22 (9.1%)	2
Metabolism and nutrition disorders
Hypophosphatemia	0/1 (0%)	0	11/16 (68.8%)	33	4/6 (66.7%)	6	15/22 (68.2%)	39
Anorexia	0/1 (0%)	0	10/16 (62.5%)	19	2/6 (33.3%)	4	12/22 (54.5%)	23
Hypokalemia	0/1 (0%)	0	9/16 (56.3%)	24	3/6 (50%)	13	12/22 (54.5%)	37
Hyponatremia	0/1 (0%)	0	9/16 (56.3%)	38	2/6 (33.3%)	2	11/22 (50%)	40
Hypoalbuminemia	0/1 (0%)	0	8/16 (50%)	30	2/6 (33.3%)	5	10/22 (45.5%)	35
Hyperglycemia	0/1 (0%)	0	7/16 (43.8%)	27	2/6 (33.3%)	4	9/22 (40.9%)	31
Hypocalcemia	0/1 (0%)	0	5/16 (31.3%)	40	1/6 (16.7%)	5	6/22 (27.3%)	45
Hypertriglyceridemia	0/1 (0%)	0	3/16 (18.8%)	4	2/6 (33.3%)	2	5/22 (22.7%)	6
Dehydration	0/1 (0%)	0	3/16 (18.8%)	4	1/6 (16.7%)	1	4/22 (18.2%)	5
Hypercalcemia	0/1 (0%)	0	2/16 (12.5%)	2	1/6 (16.7%)	1	3/22 (13.6%)	3
Hyperkalemia	0/1 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	2/22 (9.1%)	2
Hyperuricemia	0/1 (0%)	0	1/16 (6.3%)	1	1/6 (16.7%)	1	2/22 (9.1%)	2
Hypoglycemia	0/1 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	2/22 (9.1%)	2
Hypomagnesemia	0/1 (0%)	0	2/16 (12.5%)	4	0/6 (0%)	0	2/22 (9.1%)	4
Nervous system disorders
Headache	0/1 (0%)	0	2/16 (12.5%)	2	2/6 (33.3%)	2	4/22 (18.2%)	4
Dizziness	0/1 (0%)	0	3/16 (18.8%)	3	0/6 (0%)	0	3/22 (13.6%)	3
Dysgeusia	0/1 (0%)	0	1/16 (6.3%)	1	2/6 (33.3%)	2	3/22 (13.6%)	3
Renal and urinary disorders
Proteinuria	0/1 (0%)	0	9/16 (56.3%)	23	4/6 (66.7%)	8	13/22 (59.1%)	31
Hematuria	0/1 (0%)	0	4/16 (25%)	7	1/6 (16.7%)	1	5/22 (22.7%)	8
Urinary tract pain	0/1 (0%)	0	4/16 (25%)	8	0/6 (0%)	0	4/22 (18.2%)	8
Cystitis noninfective	0/1 (0%)	0	2/16 (12.5%)	4	0/6 (0%)	0	2/22 (9.1%)	4
Urinary frequency	0/1 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	2/22 (9.1%)	2
Urinary retention	0/1 (0%)	0	2/16 (12.5%)	2	0/6 (0%)	0	2/22 (9.1%)	2
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/1 (0%)	0	3/16 (18.8%)	7	1/6 (16.7%)	1	4/22 (18.2%)	8
Allergic rhinitis	0/1 (0%)	0	2/16 (12.5%)	3	0/6 (0%)	0	2/22 (9.1%)	3
Pneumothorax	0/1 (0%)	0	1/16 (6.3%)	3	1/6 (16.7%)	1	2/22 (9.1%)	4
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	0/1 (0%)	0	12/16 (75%)	32	2/6 (33.3%)	3	14/22 (63.6%)	35
Rash maculo-papular	0/1 (0%)	0	5/16 (31.3%)	6	1/6 (16.7%)	1	6/22 (27.3%)	7
Vascular disorders
Hypertension	1/1 (100%)	6	11/16 (68.8%)	60	5/6 (83.3%)	22	16/22 (72.7%)	82

Limitations/Caveats

Interim analysis to evaluate efficacy of the therapy determined that the window therapy did not meet the anticipated response, and trial accrual was stopped. Some patients continue on therapy.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.