Cyclophosphamide, Doxorubicin, Vincristine w/ Irinotecan and Temozolomide in Ewings Sarcoma

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01313884
• Collaborator: Amgen (Industry)
• Enrollment: 3
• Location: 1
• Arm: 1
• Duration (Months): 38
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The outcome of patients with metastatic Ewings Sarcoma is poor with current standard of care chemotherapy, with less than 30% survival. Based on recent encouraging pediatric literature we have designed this trial to improve the outcome of patients with metastatic Ewings sarcoma using Irinotecan and Temozolomide in addition to standard chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Bone Cancer; Ewing's Sarcoma	Drug: Irinotecan; Drug: Vincristine; Drug: Temozolomide; Drug: Doxorubicin; Drug: Cytoxan; Drug: Pegfilgrastim	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Pilot Study of Cyclophosphamide, Doxorubicin, Vincristine Alternating With Irinotecan and Temozolomide in Patients With Newly Diagnosed Metastatic Ewing's Sarcoma
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Combination Therapy Regimen A alternating with Regimen B every 21 days Regimen A: Cytoxan 1200mg/m2 Doxorubicin, starting dose 75 mg/m2 to a maximum of 450mg/m2 Vincristine, starting dose 2 mg/m2 to a maximum of 2 mg Pegfilgrastim, 6 mg subcutaneous within 24 to 48 hours after each cycle Regimen B: Irinotecan 50 mg/m2/day x 5 days Temozolomide 100 mg/m2/day x 5 days followed by 2 weeks treatment-free

Drug: Irinotecan; 50 mg/m2/day x 5 days; Other Names: Camptosar Campto ; Drug: Vincristine; 2 mg/m2 to a maximum of 2 mg; Other Names: Oncovin leurocristine ; Drug: Temozolomide; 100 mg/m2/day x 5 days followed by 2 weeks treatment-free; Other Names: Temodar Temodal ; Drug: Doxorubicin; Starting dose 75 mg/m2 to a maximum of 450mg/m2; Other Names: Adriamycin hydroxydaunorubicin ; Drug: Cytoxan; 1200 mg/m2; Other Names: Cyclophosphamide Endoxan Neosar Procytox Revimmune cytophosphane ; Drug: Pegfilgrastim; 6 mg subcutaneous within 24 to 48 hours after each Regimen A cycle; Other Names: Neulasta

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (Partial and Complete Response) [Up to 24 months]

   Response was evaluated every 12 weeks during treatment. Subjects who discontinue treatment for reasons other than disease progression or initiation of new anticancer therapy (excluding radiation therapy and surgery) response evaluated every 6 months following the last dose of study drug. Scans should be obtained every 6 months for up to 2 years (24 months) or until progression of disease or initiation of new anticancer therapy. Complete response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [24 months]

   The intended outcome is a measure of whether participants are alive without disease progression 2 years (24 months) after treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of metastatic Ewing's sarcoma.

• Patients must have measurable disease defined as lesions that can be measured by medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow disease, lesions seen on scan will not be considered measurable.

• Patients must have metastatic disease.

• Age 13 years or older

• Life expectancy of at least 3 months.

• ECOG performance status of <= 3.

• Normal hepatic function (Direct bilirubin <1.5mg/dl, SGOT or SGPT <3x upper limit of normal).

• Left Ventricular Ejection fraction of at least 50%.

• Adequate renal function: Creatinine clearance >= 50 ml/min or Serum creatinine < 1.5 x ULN for age.

• Adequate bone marrow reserve (defined as an absolute peripheral granulocyte count of

=1500/mm3, platelet count of >=75,000/mm3); unless bone marrow infiltrated with metastatic Ewing's sarcoma; ANC >= 500 and Platelet >= 50,000 mm3.

• Ability to understand and willing to sign a written informed consent document.

• Patients of childbearing potential must agree to use an effective method of contraception.

Exclusion Criteria:

• No prior chemotherapy for Ewing's sarcoma; No prior doxorubicin, temozolomide or irinotecan.

• Known hypersensitivity to any of the components of the protocol drugs.

• Clinically significant unrelated systemic illness (such as serious infections requiring active systemic intravenous antibiotic therapy; cardiovascular disease [congestive heart failure, recent myocardial infarction, unstable angina, inadequately controlled hypertension].

• No prior history of chronic diarrhea, bowel obstruction, Crohn's disease or ulcerative colitis.

• Pregnant or nursing woman are not included in the study.

• HIV-positive patients will be excluded from the study due to risk of infection or other serious side effects.

• Other medical, psychiatric or social condition incompatible with study treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• Amgen

Investigators

• Principal Investigator: Kristen N. Ganjoo, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kristen Ganjoo, Assistant Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT01313884
• Other Study ID Numbers: IRB-20323; SU-03082011-7559; SARCOMA0007
• First Posted: Mar 14, 2011
• Last Update Posted: Nov 24, 2017
• Last Verified: Dec 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Sarcoma; Sarcoma, Ewing; Bone Neoplasms; Cyclophosphamide; Temozolomide; Doxorubicin; Irinotecan; Vincristine

Study Results

Participant Flow

Arm/Group Title	Combination Therapy
Arm/Group Description	Regimen A alternate with Regimen B every 21 days Regimen A: Cytoxan=1200mg/m2 Doxorubicin=75mg/m2 (Maxiumum allowed dose 450mg/m2) Vincristine=2mg/m2 (capped at 2mg total dose) Regimen B: Irinotecan=50 mg/m2/day x 5 days Temozolomide=100 mg/m2/day x 5 days followed by two weeks of treatment-free period. Irinotecan: 50 mg/m2/day x 5 days Vincristine: 2 mg/m2 (capped at 2mg total do) Temozolomide: 100 mg/m2/day x 5 days Doxorubicin: 75 mg/m2 Cytoxan: 1200 mg/m2 Pegfilgrastim: 6 mg Mesna: 240 mg/m2 in 50 ml NS
Period Title: Overall Study
STARTED	3
COMPLETED	2
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Combination Therapy
Arm/Group Description	Regimen A alternate with Regimen B every 21 days Regimen A: Cytoxan=1200mg/m2 Doxorubicin=75mg/m2 (Maxiumum allowed dose 450mg/m2) Vincristine=2mg/m2 (capped at 2mg total dose) Regimen B: Irinotecan=50 mg/m2/day x 5 days Temozolomide=100 mg/m2/day x 5 days followed by two weeks of treatment-free period. Irinotecan: 50 mg/m2/day x 5 days Vincristine: 2 mg/m2 (capped at 2mg total do) Temozolomide: 100 mg/m2/day x 5 days Doxorubicin: 75 mg/m2 Cytoxan: 1200 mg/m2 Pegfilgrastim: 6 mg Mesna: 240 mg/m2 in 50 ml NS
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%
Not Hispanic or Latino	2 66.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 33.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 33.3%
More than one race	0 0%
Unknown or Not Reported	1 33.3%
Region of Enrollment (participants) [Number]
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Partial and Complete Response)
Description	Response was evaluated every 12 weeks during treatment. Subjects who discontinue treatment for reasons other than disease progression or initiation of new anticancer therapy (excluding radiation therapy and surgery) response evaluated every 6 months following the last dose of study drug. Scans should be obtained every 6 months for up to 2 years (24 months) or until progression of disease or initiation of new anticancer therapy. Complete response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Therapy
Arm/Group Description	Regimen A alternating with Regimen B every 21 days Regimen A: Cytoxan 1200mg/m2 Doxorubicin, starting dose 75 mg/m2 to a maximum of 450mg/m2 Vincristine, starting dose 2 mg/m2 to a maximum of 2 mg Pegfilgrastim, 6 mg subcutaneous within 24 to 48 hours after each cycle Regimen B: Irinotecan 50 mg/m2/day x 5 days Temozolomide 100 mg/m2/day x 5 days followed by 2 weeks treatment-free
Measure Participants	2
Complete Response	0 0%
Partial Response	2 66.7%

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	The intended outcome is a measure of whether participants are alive without disease progression 2 years (24 months) after treatment.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All study participants were lost to follow-up after completion of active treatment and collection of response rate, ie, within 2 years of the treatment conclusion but before documented progression. No data.

Arm/Group Title	Combination Therapy
Arm/Group Description	Regimen A alternating with Regimen B every 21 days Regimen A: Cytoxan 1200mg/m2 Doxorubicin, starting dose 75 mg/m2 to a maximum of 450mg/m2 Vincristine, starting dose 2 mg/m2 to a maximum of 2 mg Pegfilgrastim, 6 mg subcutaneous within 24 to 48 hours after each cycle Regimen B: Irinotecan 50 mg/m2/day x 5 days Temozolomide 100 mg/m2/day x 5 days followed by 2 weeks treatment-free
Measure Participants	0

Adverse Events

Time Frame	All adverse events (related and unrelated) occurring during the study (from the time the patient receives the first dose of study drug) and up to 30 days after the last dose of study medication were reported.
Adverse Event Reporting Description	Patients were asked about adverse events at every clinic visit.
Arm/Group Title	Combination Therapy
Arm/Group Description	Regimen A alternate with Regimen B every 21 days Regimen A: Cytoxan=1200mg/m2 Doxorubicin=75mg/m2 (Maxiumum allowed dose 450mg/m2) Vincristine=2mg/m2 (capped at 2mg total dose) Regimen B: Irinotecan=50 mg/m2/day x 5 days Temozolomide=100 mg/m2/day x 5 days followed by two weeks of treatment-free period. Irinotecan: 50 mg/m2/day x 5 days Vincristine: 2 mg/m2 (capped at 2mg total do) Temozolomide: 100 mg/m2/day x 5 days Doxorubicin: 75 mg/m2 Cytoxan: 1200 mg/m2 Pegfilgrastim: 6 mg Mesna: 240 mg/m2 in 50 ml NS
All Cause Mortality
	Combination Therapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Combination Therapy
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	1/3 (33.3%)	1
Thrombocytopenia	1/3 (33.3%)	1
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)	1
General disorders
Dehydration	1/3 (33.3%)	1
Fever	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Combination Therapy
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
Anemia G2	1/3 (33.3%)	2
Worsened anemia G2	1/3 (33.3%)	1
Anemia G3	1/3 (33.3%)	1
Decreased neutrophils G4	1/3 (33.3%)	1
Infection-staph epidermis bacteremia	1/3 (33.3%)	1
Platelet count decreased G1	1/3 (33.3%)	1
Platelet count decreased G2	1/3 (33.3%)	2
Platelet count decreased G4	1/3 (33.3%)	1
White blood cells decreased G2	1/3 (33.3%)	1
White blood cells decreased G4	1/3 (33.3%)	1
Eye disorders
Disc edema R eye G1	1/3 (33.3%)	1
Gastrointestinal disorders
Decreased energy G1	1/3 (33.3%)	1
Fatigue G1	1/3 (33.3%)	1
Throat pain G2	1/3 (33.3%)	1
Nausea G1	1/3 (33.3%)	1
Nausea, intermittent G1	1/3 (33.3%)	1
Nausea, intermittent G2	1/3 (33.3%)	1
Mucositis oral G1	2/3 (66.7%)	2
Oral lesions G1	1/3 (33.3%)	1
oral candidiasis G1	1/3 (33.3%)	1
Sore throat G1	1/3 (33.3%)	1
Pain with swallowing G1	1/3 (33.3%)	1
Worsening acid reflux G1	1/3 (33.3%)	1
Diarrhea G1	2/3 (66.7%)	3
Abdominal cramping G1	1/3 (33.3%)	1
Abdominal pain G1	1/3 (33.3%)	1
Intermittent diarrhea G1	1/3 (33.3%)	1
Vomiting G1	1/3 (33.3%)	1
Vomiting intermittent G1	1/3 (33.3%)	1
Constipation G1	1/3 (33.3%)	1
Nausea and vomiting G1	1/3 (33.3%)	1
General disorders
Intermittent headache G1	1/3 (33.3%)	1
Insomnia G1	1/3 (33.3%)	1
Insomnia G2	1/3 (33.3%)	1
Fever G1	1/3 (33.3%)	1
Hiccups G1	1/3 (33.3%)	1
Pain generalized 2-3 days post neulasta G1	1/3 (33.3%)	1
Metabolism and nutrition disorders
Hypokalemia G1	1/3 (33.3%)	2
Hypocalcemia intermittent G1	1/3 (33.3%)	1
Hyponatremia intermittent G1	1/3 (33.3%)	1
Intermittent hypoglycemia G1	1/3 (33.3%)	1
Hypomagnesemia G1	1/3 (33.3%)	1
Hypokalemia G1	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Hip pain L G1	1/3 (33.3%)	1
Pain sacrum (tailbone) G1	1/3 (33.3%)	1
Pain left leg G1	1/3 (33.3%)	1
Pain-lowe leg, back G2	1/3 (33.3%)	1
Nervous system disorders
Tingling at left toes G1	1/3 (33.3%)	1
Numbness on left shin G1	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough G1	1/3 (33.3%)	1
Nasal congestion G1	1/3 (33.3%)	1
Rhinorrhea G1	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Onychomycosis G2	1/3 (33.3%)	1
Hip abscess G3	1/3 (33.3%)	1
Erythema L hip G2	1/3 (33.3%)	1
Erythema groin crease G1	1/3 (33.3%)	1
Erythema left leg G1	1/3 (33.3%)	1
Edema left leg pitting 2+, G1	1/3 (33.3%)	1
Hyperpigmentation left knee G1	1/3 (33.3%)	1

Limitations/Caveats

Study did not reach primary objective; study didn't accrue enough patients.

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.