Trial Outcomes & Findings for Dacarbazine for Metastatic Soft Tissue and Bone Sarcoma (NCT NCT00802880)

NCT ID: NCT00802880

Last Updated: 2017-02-13

Results Overview

* Complete response (CR): disappearance of all target lesions, disappearance of all non-target lesions, normalization of tumor level marker * Partial response (PR): at least 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, persistence of one or more non-target lesion and/or maintenance of tumor marker level above the upper limits of normal * Stable disease (SD): neither sufficient shrinkage in target lesions to qualify for PR nor sufficient increase to qualify for progressive disease taking as references the smallest sum LD since the treatment started, persistence of one or more non-target lesion and/or maintenance of tumor marker level above the normal limits of normal * Progressive disease (PD): at least 20% increase in the sum of the LD of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

After completion of 3 cycles

Results posted on

2017-02-13

Participant Flow

The study opened to accrual on 03/16/2009 and closed to accrual on 12/15/2014.

Participant milestones

Participant milestones
Measure
Dacarbazine
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Overall Study
STARTED
80
Overall Study
COMPLETED
80
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dacarbazine for Metastatic Soft Tissue and Bone Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Dacarbazine
n=80 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Age, Continuous
53 years
n=39 Participants
Gender
Female
40 Participants
n=39 Participants
Gender
Male
40 Participants
n=39 Participants
Region of Enrollment
United States
80 participants
n=39 Participants

PRIMARY outcome

Timeframe: After completion of 3 cycles

Population: 3 patients failed to complete 3 cycles of treatment due to toxicity. 22 patients failed to complete 3 cycles of treatment due to progressive disease. 1 patient only had PET scan.

* Complete response (CR): disappearance of all target lesions, disappearance of all non-target lesions, normalization of tumor level marker * Partial response (PR): at least 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, persistence of one or more non-target lesion and/or maintenance of tumor marker level above the upper limits of normal * Stable disease (SD): neither sufficient shrinkage in target lesions to qualify for PR nor sufficient increase to qualify for progressive disease taking as references the smallest sum LD since the treatment started, persistence of one or more non-target lesion and/or maintenance of tumor marker level above the normal limits of normal * Progressive disease (PD): at least 20% increase in the sum of the LD of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

Outcome measures

Outcome measures
Measure
Dacarbazine
n=54 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Best Anatomical Tumor Response
Complete response
0 participants
Best Anatomical Tumor Response
Partial response
2 participants
Best Anatomical Tumor Response
Stable disease
22 participants
Best Anatomical Tumor Response
Progressive disease
30 participants

SECONDARY outcome

Timeframe: Completion of 6 cycles of treatment (18 weeks)

* Grade 3 neutropenia = absolute neutrophil count of \<1000 - 500/mm\^3 * Grade 4 neutropenia = absolute neutrophil count of \<500/mm\^3

Outcome measures

Outcome measures
Measure
Dacarbazine
n=80 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Rate of Neutropenia (Grade 3/4)
7.5 percentage of participants

SECONDARY outcome

Timeframe: Completion of 6 cycles of treatment (18 weeks)

Approximately 18 weeks

Outcome measures

Outcome measures
Measure
Dacarbazine
n=80 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Rate of Nausea/Emesis (Any Grade)
22.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and after every three cycles of treatment (up to 1 year)

Population: The lower confidence limit is 85% and the upper confidence limit is 95%. 51 patients evaluable at baseline, 50 patients evaluable at end of cycle 3, 20 patients evaluable at end of cycle 6, 7 patients evaluable at end of cycle 9, and 5 patients evaluable at end of cycle 12.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=51 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Comparison of the SUV at up to 3 Tumor Sites
Baseline
7.42 standard uptake value
Interval 6.2 to 8.83
Comparison of the SUV at up to 3 Tumor Sites
End of cycle 3
7.57 standard uptake value
Interval 6.34 to 9.01
Comparison of the SUV at up to 3 Tumor Sites
End of cycle 6
7.7 standard uptake value
Interval 6.33 to 9.34
Comparison of the SUV at up to 3 Tumor Sites
End of cycle 9
6.89 standard uptake value
Interval 5.39 to 8.74
Comparison of the SUV at up to 3 Tumor Sites
End of cycle 12
7.48 standard uptake value
Interval 5.68 to 9.76

SECONDARY outcome

Timeframe: After completion of 3 cycles

Population: 29 patients were not evaluable due to various reasons such as toxicity, progressive disease prior to completion of cycle 3, patient refusal, and no target lesions on PET scan.

* Complete metabolic response (CMR)-complete resolution of all metabolically active target and non-target lesions, and no interval development of new lesions. * Partial metabolic response (PMR) * Target lesions: 20% or greater decrease in maximum SUV from baseline. No unequivocal metabolic progression of non-target disease, and no unequivocal new lesions. * Non-target lesions: decrease in total number of non-target lesions, without complete resolution of metabolically active disease, or unequivocal decrease in degree of FDG activity within \>50% of the lesions. No unequivocal new lesions. * Stable metabolic disease (SMD): does not qualify for CMR, PMR, or PMD. * Progressive metabolic disease (PMD): * Unequivocal development of one more new metabolically active lesions * Target lesion: 20% or greater increase in maximum SUV from baseline. * Non-target lesions: unequivocal increase in FDG activity

Outcome measures

Outcome measures
Measure
Dacarbazine
n=51 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Overall Tumor Metabolic Response
CMR
0 participants
Overall Tumor Metabolic Response
PMR
4 participants
Overall Tumor Metabolic Response
SMD
13 participants
Overall Tumor Metabolic Response
PMD
34 participants

SECONDARY outcome

Timeframe: After completion of 3 cycles

Population: 31 patients were not evaluable due to various reasons such as toxicity, progressive disease prior to completion of cycle 3, patient refusal, and no target lesions on PET scan.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=4 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
n=12 Participants
Progressive Metabolic Disease
n=33 Participants
Total
n=49 Participants
Correlate the Tumor Metabolic Response Rate With the Tumor Anatomic Response Rate
PR
1 participants
0 participants
1 participants
2 participants
Correlate the Tumor Metabolic Response Rate With the Tumor Anatomic Response Rate
SD
2 participants
10 participants
8 participants
20 participants
Correlate the Tumor Metabolic Response Rate With the Tumor Anatomic Response Rate
PD
1 participants
2 participants
24 participants
27 participants
Correlate the Tumor Metabolic Response Rate With the Tumor Anatomic Response Rate
Total
4 participants
12 participants
33 participants
49 participants

SECONDARY outcome

Timeframe: 12 months

Population: Only 6 patients were evaluable for response at the end of 12 cycles.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=6 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Overall Disease Control Rate
Complete response
0 participants
Overall Disease Control Rate
Partial response
0 participants
Overall Disease Control Rate
Stable disease
5 participants
Overall Disease Control Rate
Progressive disease
1 participants

SECONDARY outcome

Timeframe: Until completion of follow-up (estimated to be 1 year)

Population: 10 patient observations with invalid time or censoring values were not included.

-Progression - At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=70 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Time to Progression (TTP)
2.07 months
Interval 1.84 to 2.3

SECONDARY outcome

Timeframe: Until completion of follow-up or patient death (estimated to be 1 year)

Population: One patient with invalid time or censoring value was not included.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=79 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Overall Survival
8.09 months
Interval 5.56 to 9.74

SECONDARY outcome

Timeframe: Completion of follow-up (estimated to be 1 year)

Population: 29 patients were not evaluable due to various reasons such as toxicity, progressive disease prior to completion of cycle 3, patient refusal, and no anatomic response recorded.

-Progression - At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=51 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Correlate the Time to Progression With Best Anatomic Response
Progressive disease
1.97 months
Interval 1.84 to 2.07
Correlate the Time to Progression With Best Anatomic Response
Partial response
NA months
Interval 9.41 to
The median and upper confidence level were not estimable due to the limited number of events.
Correlate the Time to Progression With Best Anatomic Response
Stable disease
4.14 months
Interval 3.91 to 6.94

SECONDARY outcome

Timeframe: Completion of follow-up (estimated to be 1 year)

Population: 31 patients were not evaluable due to various reasons such as toxicity, progressive disease prior to completion of cycle 3, patient refusal, and no target lesions on PET scan.

-Progression - At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=49 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Correlate Time to Progression With Best Metabolic Response
Partial metabolic response
3.95 months
Interval 1.61 to
The upper confidence level was not estimable due to the limited number of events.
Correlate Time to Progression With Best Metabolic Response
Stable metabolic disease
5.30 months
Interval 2.53 to 9.41
Correlate Time to Progression With Best Metabolic Response
Progressive metabolic disease
2.07 months
Interval 1.84 to 2.3

SECONDARY outcome

Timeframe: Completion of follow-up (estimated to be 1 year)

Population: 26 patients were not evaluable for this outcome measure for various reasons including unknown survival status, progressive disease prior to cycle 3, no anatomic response noted, and toxicity.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=54 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Correlate Overall Survival With Best Anatomic Response
Partial response
18.16 months
The lower and upper confidence levels were not estimable due to the limited number of events. Only two patients had partial response and only one of them died within the time frame of the study.
Correlate Overall Survival With Best Anatomic Response
Stable disease
14.77 months
Interval 8.75 to 23.85
Correlate Overall Survival With Best Anatomic Response
Progressive disease
7.96 months
Interval 5.72 to 10.46

SECONDARY outcome

Timeframe: Completion of follow-up (estimated to be 1 year)

Population: 28 patients were not evaluable for this outcome measure due to various reason such as progressive disease prior to cycle 3, unknown survival status, no target lesion on PET scan, and toxicity.

Outcome measures

Outcome measures
Measure
Dacarbazine
n=52 Participants
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Stable Metabolic Disease
Progressive Metabolic Disease
Total
Correlate Overall Survival With Best Metabolic Response
Partial metabolic response
18.16 months
Interval 7.3 to 25.79
Correlate Overall Survival With Best Metabolic Response
Stable metabolic disease
18.59 months
Interval 6.91 to 44.01
Correlate Overall Survival With Best Metabolic Response
Progressive metabolic disease
8.75 months
Interval 6.05 to 12.8

Adverse Events

Dacarbazine

Serious events: 16 serious events
Other events: 80 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Dacarbazine
n=80 participants at risk
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Infections and infestations
Upper respiratory infection
1.2%
1/80
Infections and infestations
Urinary tract infection
1.2%
1/80
General disorders
Disease progression
1.2%
1/80
General disorders
Death
1.2%
1/80
Injury, poisoning and procedural complications
Fracture
1.2%
1/80
Respiratory, thoracic and mediastinal disorders
Dyspnea
5.0%
4/80
Respiratory, thoracic and mediastinal disorders
Lung hemorrhage
1.2%
1/80
Hepatobiliary disorders
Cholecystitis
1.2%
1/80
Gastrointestinal disorders
Diarrhea
1.2%
1/80
Nervous system disorders
Neuropathy - motor
1.2%
1/80
Gastrointestinal disorders
Abdominal hemorrhage
1.2%
1/80
Investigations
Thrombocytopenia
1.2%
1/80
Vascular disorders
Hypotension
1.2%
1/80
Blood and lymphatic system disorders
Hemoglobin
1.2%
1/80
Gastrointestinal disorders
Abdominal pain
1.2%
1/80
Musculoskeletal and connective tissue disorders
Neck pain
1.2%
1/80
Gastrointestinal disorders
Ascites
1.2%
1/80
Immune system disorders
Allergic reaction
1.2%
1/80

Other adverse events

Other adverse events
Measure
Dacarbazine
n=80 participants at risk
Dacarbazine 850 mg/m\^2 IV Day 1 of each 21 day cycle.
Respiratory, thoracic and mediastinal disorders
Nose hemorrhage
1.2%
1/80
Cardiac disorders
Palpitations
1.2%
1/80
Respiratory, thoracic and mediastinal disorders
Pericardial effusion
1.2%
1/80
Metabolism and nutrition disorders
Phosphorus - low
3.8%
3/80
Skin and subcutaneous tissue disorders
Photosensitivity
2.5%
2/80
Investigations
Platelets
41.2%
33/80
Gastrointestinal disorders
Abodominal pain
11.2%
9/80
Metabolism and nutrition disorders
Acidosis
1.2%
1/80
Skin and subcutaneous tissue disorders
Acneiform rash
1.2%
1/80
Metabolism and nutrition disorders
Albumin - low
33.8%
27/80
Investigations
Alkaline phosphatase
23.8%
19/80
Immune system disorders
Allergic reaction/hypersensitivity
2.5%
2/80
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
6.2%
5/80
Skin and subcutaneous tissue disorders
Alopecia
5.0%
4/80
Eye disorders
Anisocoria
1.2%
1/80
Gastrointestinal disorders
Anorexia
15.0%
12/80
Musculoskeletal and connective tissue disorders
Arthralgia
1.2%
1/80
Cardiac disorders
Atrial fibrillation
1.2%
1/80
Investigations
Bilirubin
5.0%
4/80
Gastrointestinal disorders
Bloating
1.2%
1/80
Infections and infestations
Boil
2.5%
2/80
Musculoskeletal and connective tissue disorders
Bone pain
28.7%
23/80
Cardiac disorders
Brachycardia
1.2%
1/80
Respiratory, thoracic and mediastinal disorders
Bronchospasm: wheezing
2.5%
2/80
Injury, poisoning and procedural complications
Bruising
2.5%
2/80
Metabolism and nutrition disorders
Calcium - high
2.5%
2/80
Metabolism and nutrition disorders
Calcium - low
36.2%
29/80
Cardiac disorders
Chest pain
6.2%
5/80
General disorders
Chills
1.2%
1/80
Nervous system disorders
Cognitive disturbance
1.2%
1/80
General disorders
Cold sore
1.2%
1/80
Psychiatric disorders
Confusion
2.5%
2/80
Respiratory, thoracic and mediastinal disorders
Congestion
2.5%
2/80
Gastrointestinal disorders
Constipation
23.8%
19/80
Musculoskeletal and connective tissue disorders
Contracture
1.2%
1/80
Respiratory, thoracic and mediastinal disorders
Cough
15.0%
12/80
Investigations
Creatinine
13.8%
11/80
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cyst
1.2%
1/80
Metabolism and nutrition disorders
Dehydration
3.8%
3/80
Psychiatric disorders
Delirium
1.2%
1/80
Psychiatric disorders
Depression
1.2%
1/80
Skin and subcutaneous tissue disorders
Diaphoresis
1.2%
1/80
Gastrointestinal disorders
Diarrhea
16.2%
13/80
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease pain
21.2%
17/80
Nervous system disorders
Dizziness
3.8%
3/80
Gastrointestinal disorders
Dry mouth
1.2%
1/80
Gastrointestinal disorders
Dyspepsia/heartburn
2.5%
2/80
Respiratory, thoracic and mediastinal disorders
Dyspnea
18.8%
15/80
General disorders
Edema
27.5%
22/80
Investigations
Elevated PTT
7.5%
6/80
Investigations
Elevated troponin I
1.2%
1/80
Skin and subcutaneous tissue disorders
Erythema
1.2%
1/80
Gastrointestinal disorders
Esophageal obstruction
1.2%
1/80
Musculoskeletal and connective tissue disorders
Extremity pain
3.8%
3/80
General disorders
Face pain
1.2%
1/80
Injury, poisoning and procedural complications
Fall
2.5%
2/80
General disorders
Fatigue
53.8%
43/80
General disorders
Fever
6.2%
5/80
Gastrointestinal disorders
Flatulence
2.5%
2/80
Eye disorders
Floaters
1.2%
1/80
General disorders
Flu like syndrome
2.5%
2/80
Renal and urinary disorders
Frothy urine
1.2%
1/80
Gastrointestinal disorders
GI abdominal hemorrhage
3.8%
3/80
Metabolism and nutrition disorders
Glucose - high
27.5%
22/80
Metabolism and nutrition disorders
Glucose - low
6.2%
5/80
Musculoskeletal and connective tissue disorders
Gout
2.5%
2/80
Nervous system disorders
Headache
5.0%
4/80
Vascular disorders
Hematoma
1.2%
1/80
Renal and urinary disorders
Hematuria
1.2%
1/80
Blood and lymphatic system disorders
Hemoglobin
71.2%
57/80
Vascular disorders
Hot flashes
3.8%
3/80
Metabolism and nutrition disorders
Hypermagnesemia
1.2%
1/80
Vascular disorders
Hypertension
6.2%
5/80
Investigations
Hypertriglyceridemia
1.2%
1/80
Investigations
INR
11.2%
9/80
Vascular disorders
Inferior vena cava thrombus
1.2%
1/80
Psychiatric disorders
Insomnia
7.5%
6/80
Musculoskeletal and connective tissue disorders
Intraspinal hematoma
1.2%
1/80
Eye disorders
Keratitis
1.2%
1/80
Investigations
Leukocytes (WBC)
30.0%
24/80
Investigations
Lymphopenia
67.5%
54/80
Nervous system disorders
Memory impairment
1.2%
1/80
Psychiatric disorders
Mood alteration - agitation
1.2%
1/80
Psychiatric disorders
Mood alteration - anxiety
3.8%
3/80
Gastrointestinal disorders
Mucositis
3.8%
3/80
Musculoskeletal and connective tissue disorders
Muscular weakness
3.8%
3/80
Musculoskeletal and connective tissue disorders
Myalgia
1.2%
1/80
Gastrointestinal disorders
Nausea
22.5%
18/80
Musculoskeletal and connective tissue disorders
Neck pain
1.2%
1/80
Nervous system disorders
Neuropathy (sensory)
8.8%
7/80
Infections and infestations
Neutropenic fever
1.2%
1/80
Investigations
Neutrophils (ANC)
18.8%
15/80
Respiratory, thoracic and mediastinal disorders
Pleural effusion
3.8%
3/80
Respiratory, thoracic and mediastinal disorders
Pnemonia
5.0%
4/80
Respiratory, thoracic and mediastinal disorders
Pneumothorax
1.2%
1/80
Vascular disorders
Portal vein thrombosis
1.2%
1/80
Metabolism and nutrition disorders
Potassium - high
5.0%
4/80
Metabolism and nutrition disorders
Potassium - low
15.0%
12/80
Renal and urinary disorders
Proteinuria
2.5%
2/80
Vascular disorders
Pulmonary embolism
1.2%
1/80
Respiratory, thoracic and mediastinal disorders
Pulmonary hemorrhage
2.5%
2/80
Skin and subcutaneous tissue disorders
Rash
5.0%
4/80
Gastrointestinal disorders
Reflux gastritis
1.2%
1/80
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
1.2%
1/80
Investigations
SGOT (AST)
20.0%
16/80
Investigations
SGPT (ALT)
18.8%
15/80
Nervous system disorders
Seizure
3.8%
3/80
Musculoskeletal and connective tissue disorders
Shoulder/back pain
5.0%
4/80
Infections and infestations
Sinusitis
1.2%
1/80
Metabolism and nutrition disorders
Sodium - high
7.5%
6/80
Metabolism and nutrition disorders
Sodium - low
26.2%
21/80
Nervous system disorders
Speech impairment
1.2%
1/80
General disorders
Swelling - face
1.2%
1/80
Cardiac disorders
Tachycardia
6.2%
5/80
Gastrointestinal disorders
Taste alterations
3.8%
3/80
Infections and infestations
Thrush
1.2%
1/80
Gastrointestinal disorders
Ulcer: GI duodenum
1.2%
1/80
Infections and infestations
Upper respiratory infection
6.2%
5/80
Renal and urinary disorders
Urinary frequency/urgency
2.5%
2/80
Infections and infestations
Urinary tract infection
6.2%
5/80
Renal and urinary disorders
Urine color change
1.2%
1/80
Respiratory, thoracic and mediastinal disorders
Voice changes
1.2%
1/80
Gastrointestinal disorders
Vomiting
15.0%
12/80
Investigations
Weight loss
3.8%
3/80

Additional Information

Brian Van Tine, M.D., Ph.D.

Washington University School of Medicine

Phone: 314-362-5817

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place