DESMOPAZ: PAZOPANIB Efficacy and Tolerance in Desmoids Tumors

• Sponsor: Institut Bergonié (Other)
• Overall Status: Completed
• CT.gov ID: NCT01876082
• Collaborator: (none)
• Enrollment: 72
• Location: 1
• Arms: 2
• Actual Duration (Months): 83.4
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Desmoids tumors are benign soft tissues tumors characterized by aggressiveness and potential local recurrence. There is a female predominance with a sex ratio of 2/1 and median age at diagnosis is about 30 years.

Only a complete surgical excision is recommended in desmoids tumors. Some forms of desmoid tumors are recurrent and/or symptomatic and are not accessible to a conservative surgical treatment. In these clinical situations, only a medical treatment may achieve tumor control and quality of life maintenance. Place of systemic treatments in the management of desmoids tumors is poorly evaluated. Regarding chemotherapy, methotrexate and vinblastine protocol is actually the best evaluated combination, which allowed observing objective response rate between 40 and 75%. Toxicity was mainly marked by the risk of haematological toxicity.

Pazopanib is an inhibitor of multi-target tyrosine kinase, in oral form, with selective type receptors -1, -2 and -3 of VEGF receptors on the PDGFA and B, and c-Kit. It is currently under clinical development in humans in the treatment of several tumor types.

Condition or Disease	Intervention/Treatment	Phase
Progressive Desmoids Tumors	Drug: PAZOPANIB treatment; Drug: Active Comparator: Vinblastine and Methotrexate	Phase 2

Detailed Description

This is a Phase II, randomized, multicenter, open label trial, evaluating efficacy and safety of pazopanib versus a chemotherapy protocol combining methotrexate and vinblastine in progressive and symptomatic desmoid tumors.

This study will include 72 patients in 15 centers of the French Sarcoma Group.

Patients will be treated according to therapeutic strategy allocated by randomization until documented RECIST progression and for a maximum of 12 months :

• Arm A = experimental strategy: daily oral administration of pazopanib.

• Arm B = reference strategy: methotrexate-vinblastine.

In case of documented radiological progression (RECIST criteria):

• Patients initially included in arm A will have the opportunity, as determined by the investigator, to receive arm B treatment, or leave the study,

• Patients initially included in arm B will have the opportunity, as determined by the investigator, to receive arm A treatment, or leave the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PAZOPANIB Efficacy and Tolerance in Desmoids Tumors : Phase 2 Clinical Trial
• Actual Study Start Date: Sep 18, 2012
• Actual Primary Completion Date: Mar 1, 2018
• Actual Study Completion Date: Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PAZOPANIB Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	Drug: PAZOPANIB treatment; Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum
Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.	Drug: Active Comparator: Vinblastine and Methotrexate; Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Remaining Alive and Progression-free at 6 Months as Per RECIST 1.1 After the Day of Randomisation (6-month Non-progression Rate). [6 months]

   Percentage of patients remaining alive and progression-free at 6 months as per RECIST 1.1 after the day of randomisation. Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Percentage of Patients Remaining Alive With Best Overall Response as Per RECIST v1.1. [1 year]

   Best overall response is defined as the best response across all time points (RECIST v1.1). The best overall response is determined once all the data for the participant is known. Each patient has been assigned one of the following categories (RECIST 1.1): complete response (disappearance of all target lesions); partial response (>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); progression (20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and stable disease (nor CR, PR or progression).

2. Progression-free Survival [Randomization to disease progression, or death due to any cause, whichever occurs first; until 2 years after the last patient randomized.]

   Progression-free survival (PFS) defined as the time from randomization to the first documented progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first. Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact. Progression is assessed as per RECIST v1.1. Progression-free survival is estimated as a function of time using Kaplan-Meier method. 1- and 2-year PFS rates were reported.

3. Overall Survival [Randomization to disease progression, or death due to any cause, whichever occurs first; until 2 years after the last patient randomized.]

   Overall survival (OS) defined as the time from randomization to death (due to any cause). Patients alive were censored at the date of last follow-up or last patient contact. Overall survival was estimated as a function of time using Kaplan-Meier method.1- and 2-Year OS rates were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written consent;

2. Age ≥ 18 years;

3. ECOG ≤ 1;

4. Histologically confirmed desmoid tumor;

5. Disease progression before the patient's inclusion : completion of two similar imaging obtained within 6 months apart (a tolerance of 6 weeks is accepted)

6. Measurable target lesion (RECIST criteria) ;

7. Left ventricular ejection fraction (MUGA or ECHO) within the normal;

8. Normal hematological, renal and liver functions :

9. Hemoglobin ≥ 9 g / dl; neutrophils ≥ 1.5 x 109 / l; platelets ≥ 100 x 109 / l; prothrombin time or INR1 ≤ 1.2 ULN or activated partial thromboplastin time ≤ 1.2 ULN;

10. Amino alanine transferase and aspartate amino transferase ≤ 2.5 ULN;

11. Total bilirubin ≤ 1.5 ULN;

12. Creatinine ≤ 1.5 mg/dl or, if creatinine> 1.5 mg/dl, Creatinine clearance ≥ 50 m/min;

13. Urinary protein / urinary creatinine (Pu / Cu) <1. If PU/Cu ≥ 1, patients must have a proteinuria below 1g/24 h

14. Women are eligible provided they:

15. Physiologically incapable of childbearing (hysterectomy, oophorectomy, bilateral tubal ligation, menopause).

16. Of childbearing age if they have had a negative pregnancy test in the week before the first dose of treatment.

17. Women of childbearing potential and men must agree to take an adequate method of contraception. Permitted contraceptive methods : IUD with a documented failure rate of 1% per year, Partner's vasectomy, complete sex abstinence (for 14 days before inclusion, the test period and after cessation of treatment according to the chemotherapy as described below), dual contraception, oral contraceptives.

Effective contraception must be implemented:

• Up to 6 months after treatment with vinblastine

• Up to 5 months after treatment with Methotrexate for men and up to 3 months after treatment with Methotrexate for women

• For the duration of treatment with Pazopanib;

1. Affiliated to a social security system

Exclusion Criteria:

1. Personal history of malignancy except:

2. Cervical intraepithelial neoplasia;

3. Skin basal cell carcinoma;

4. Treated localized prostate carcinoma with PSA <1;

5. Neoplasia treated with curative intent, in remission for at least five years and considered at low risk of relapse.

6. Pretreatement by Pazopanib or Methotrexate - vinblastine;

7. Known allergy to Pazopanib, Methotrexate or vinblastine;

8. Histological sampling not available for review or biological study;

9. Clinical abnormalities which may increase the risk of gastric bleeding (not exhaustive list);

10. Gastric tumor with known risk of bleeding;

11. Inflammatory bowel disease or other gastrointestinal disease may increase the risk of gastric perforation.

12. Pathologies that can lead to impaired intestinal absorption (not exhaustive):

13. Malabsorption;

14. Major resection of small intestine or stomach.

15. Active uncontrolled infectious disease;

16. Corrected QT interval> 480 ms;

17. History of cardiovascular disease in the last 6 months:

18. Cardiac angioplasty;

19. Myocardial infarction;

20. Unstable angina;

21. Bypass surgery;

22. Symptomatic arterial disease.

23. Congestive heart failure grade II, III or IV according to the New York Hearth Association (NYHA) classification;

24. Uncontrolled arterial hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);

25. History of stroke or transient ischemic attack, pulmonary embolism or deep vein thrombosis not treated, within 6 months;

26. History of major surgery or trauma within 28 days prior the first day of treatment, or presence of a wound, fracture or non-healed ulcer;

27. Evidence of active bleeding or bleeding tendency;

28. Known endobronchial lesions and / or infiltrative lesions of the large vessels lung;

29. History of hemoptysis of more than 2.5 ml in the eight weeks preceding the first day of chemotherapy;

30. Pulmonary dysfunction, asthma, emphysema, chronic obstructive pulmonary bronchitis, pneumonia, pneumothorax, pulmonary contusion, hemothorax, distress acute respiratory syndrome, pulmonary fibrosis;

31. Severe renal dysfunction;

32. Severe hepatic dysfunction;

33. History of psoriasis, rheumatoid arthritis, alcoholism, illness or chronic liver dysfunction;

34. Any pre-existing severe or unstable medical or psychiatric condition, or other condition that may interfere with patient safety, the collection of its informed consent or adherence to treatment;

35. Patient who refused or could not stop taking banned drugs for at least 14 days (or 5 half-lives of the drug) before the first day of start of chemotherapy and for the duration of the study;

36. During cancer treatment:

37. Radiotherapy, surgery or tumor embolization within 14 days before the 1st dose of pazobanib (arm A) or chemotherapy methotrexate, vinblastine (arm B);

38. Chemotherapy, immunotherapy, biological treatment, experimental or hormone therapy within 14 days or 5 half-lives of medication before the first day of the pazopanib (arm A) or chemotherapy with methotrexate, vinblastine (arm B).

39. History of cancer treatment toxicity> grade 1 and / or whose the intensity increases, outside of alopecia.

40. Pregnancy and lactation

41. Concomitant treatment which can't be interrupted or replaced and which is not indicated with methotrexate:

42. Probenecid (alone or associated with sulfamethoxazole),

43. Trimethoprim,

44. Acetylsalicylic acid (for methotrexate doses above 20 mg per week with the acetylsalicylic acid and used at doses analgesics or antipyretics (≥ 500 mg per dose and/or <3 g per day)or anti-inflammatory (≥ 1 g per dose and / or > 3 g per day),

45. Phenylbutazone,

46. Yellow fever vaccine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut Bergonié	Bordeaux	Aquitaine	France	33000

Sponsors and Collaborators

• Institut Bergonié

Investigators

• Study Chair: ITALIANO Antoine, MD, Institut Bergonié

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 19, 2016

More Information

Additional Information:

• Registre des essais cliniques de l'INCa
• Site internet du promoteur, l'Institut Bergonié

Publications

None provided.

• Responsible Party: Institut Bergonié
• ClinicalTrials.gov Identifier: NCT01876082
• Other Study ID Numbers: IB2011-03
• First Posted: Jun 12, 2013
• Last Update Posted: Mar 5, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Institut Bergonié: Desmoids tumors; Pazopanib; Phase 2 clinical trial; Cross over
• Additional relevant MeSH terms: Fibromatosis, Aggressive; Methotrexate; Vinblastine

Study Results

Participant Flow

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Period Title: Overall Study
STARTED	48	24
Safety Population	48	22
COMPLETED	46	20
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate	Total
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.	Total of all reporting groups
Overall Participants	48	24	72
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	35.5	42.5	39.8
Sex: Female, Male (Count of Participants)
Female	31 64.6%	15 62.5%	46 63.9%
Male	17 35.4%	9 37.5%	26 36.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
France	48 100%	24 100%	72 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Remaining Alive and Progression-free at 6 Months as Per RECIST 1.1 After the Day of Randomisation (6-month Non-progression Rate).
Description	Percentage of patients remaining alive and progression-free at 6 months as per RECIST 1.1 after the day of randomisation. Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Measure Participants	46	20
Number (95% Confidence Interval) [percentage of participants]	84.8 176.7%	45.0 187.5%

2. Secondary Outcome

Title	Percentage of Patients Remaining Alive With Best Overall Response as Per RECIST v1.1.
Description	Best overall response is defined as the best response across all time points (RECIST v1.1). The best overall response is determined once all the data for the participant is known. Each patient has been assigned one of the following categories (RECIST 1.1): complete response (disappearance of all target lesions); partial response (>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); progression (20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and stable disease (nor CR, PR or progression).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Measure Participants	46	20
Complete response	0 0%	0 0%
Partial response	41.3 86%	30.0 125%
Stable disease	54.4 113.3%	45.0 187.5%
Progression	4.4 9.2%	20.0 83.3%
Inevaluable for response	0 0%	5.0 20.8%

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) defined as the time from randomization to the first documented progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first. Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact. Progression is assessed as per RECIST v1.1. Progression-free survival is estimated as a function of time using Kaplan-Meier method. 1- and 2-year PFS rates were reported.
Time Frame	Randomization to disease progression, or death due to any cause, whichever occurs first; until 2 years after the last patient randomized.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Measure Participants	46	20
PFS rate at 1 year	84.8 176.7%	68.6 285.8%
PFS rate at 2 years	65.2 135.8%	68.6 285.8%

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) defined as the time from randomization to death (due to any cause). Patients alive were censored at the date of last follow-up or last patient contact. Overall survival was estimated as a function of time using Kaplan-Meier method.1- and 2-Year OS rates were reported.
Time Frame	Randomization to disease progression, or death due to any cause, whichever occurs first; until 2 years after the last patient randomized.

Outcome Measure Data

Analysis Population Description

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Measure Participants	46	20
OS rate at 1 year	100.0 208.3%	100.0 416.7%
OS rate at 2 years	97.8 203.8%	100.0 416.7%

Adverse Events

Time Frame	2 years
Arm/Group Title	PAZOPANIB		Vinblastine and Methotrexate
Arm/Group Description	Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib 800 mg per day oral administration at least 1 hour before or 2 hours after a meal, until disease progression or for 12 months maximum		vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
All Cause Mortality
	PAZOPANIB		Vinblastine and Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/48 (2.1%)		0/22 (0%)
Serious Adverse Events
	PAZOPANIB		Vinblastine and Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/48 (41.7%)		10/22 (45.5%)
Blood and lymphatic system disorders
Anemia	1/48 (2.1%)	1	0/22 (0%)	0
Blood and lymphatic system disorders - Other, specify	1/48 (2.1%)	1	0/22 (0%)	0
Eye disorders
Retinal detachment	1/48 (2.1%)	1	0/22 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/48 (2.1%)	1	2/22 (9.1%)	2
Diarrhea	1/48 (2.1%)	1	0/22 (0%)	0
Duodenal stenosis	0/48 (0%)	0	1/22 (4.5%)	1
Gastrointestinal pain	1/48 (2.1%)	1	0/22 (0%)	0
Gastrointestinal disorders - Other, specify	1/48 (2.1%)	1	0/22 (0%)	0
General disorders
Fever	1/48 (2.1%)	1	0/22 (0%)	0
Infusion site extravasation	0/48 (0%)	0	1/22 (4.5%)	1
General disorders and administration site conditions - Other, specify	1/48 (2.1%)	1	0/22 (0%)	0
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	0/48 (0%)	0	2/22 (9.1%)	2
Infections and infestations
Sepsis	1/48 (2.1%)	1	0/22 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/48 (2.1%)	1	0/22 (0%)	0
Investigations
Alanine aminotransferase increased	0/48 (0%)	0	2/22 (9.1%)	2
Neutrophil count decreased	2/48 (4.2%)	2	1/22 (4.5%)	1
Metabolism and nutrition disorders
Hypercalcemia	1/48 (2.1%)	1	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/48 (0%)	0	1/22 (4.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/48 (2.1%)	1	0/22 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/48 (2.1%)	2	1/22 (4.5%)	1
Nervous system disorders
Paresthesia	1/48 (2.1%)	1	0/22 (0%)	0
Nervous system disorders - Other, specify	0/48 (0%)	0	1/22 (4.5%)	1
Psychiatric disorders
Depression	0/48 (0%)	0	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify	1/48 (2.1%)	1	0/22 (0%)	0
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/48 (2.1%)	1	0/22 (0%)	0
Vascular disorders
Hematoma	1/48 (2.1%)	1	0/22 (0%)	0
Hypertension	2/48 (4.2%)	2	0/22 (0%)	0
Thromboembolic event	1/48 (2.1%)	1	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	PAZOPANIB		Vinblastine and Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/48 (100%)		22/22 (100%)
Blood and lymphatic system disorders
Anemia	2/48 (4.2%)	2	5/22 (22.7%)	7
Endocrine disorders
Hypothyroidism	12/48 (25%)	13	0/22 (0%)	0
Eye disorders - Other, specify	7/48 (14.6%)	8	1/22 (4.5%)	1
Gastrointestinal disorders
Abdominal pain	16/48 (33.3%)	29	6/22 (27.3%)	6
Bloating	4/48 (8.3%)	4	2/22 (9.1%)	2
Constipation	6/48 (12.5%)	6	12/22 (54.5%)	15
Diarrhea	37/48 (77.1%)	60	9/22 (40.9%)	10
Dry mouth	4/48 (8.3%)	4	1/22 (4.5%)	1
Gastroesophageal reflux disease	1/48 (2.1%)	1	2/22 (9.1%)	2
Gastrointestinal disorders - Other, specify	9/48 (18.8%)	12	2/22 (9.1%)	2
Gastrointestinal pain	8/48 (16.7%)	9	1/22 (4.5%)	1
Mucositis oral	13/48 (27.1%)	17	7/22 (31.8%)	11
Nausea	26/48 (54.2%)	34	16/22 (72.7%)	19
Stomach pain	0/48 (0%)	0	4/22 (18.2%)	4
Toothache	3/48 (6.3%)	3	1/22 (4.5%)	3
Vomiting	15/48 (31.3%)	24	6/22 (27.3%)	6
General disorders
Edema limbs	3/48 (6.3%)	3	1/22 (4.5%)	2
Fatigue	40/48 (83.3%)	45	15/22 (68.2%)	19
Fever	3/48 (6.3%)	4	2/22 (9.1%)	2
Flu like symptoms	3/48 (6.3%)	3	1/22 (4.5%)	1
Non-cardiac chest pain	2/48 (4.2%)	2	2/22 (9.1%)	2
Pain	4/48 (8.3%)	4	2/22 (9.1%)	2
Infections and infestations
Infections and infestations - Other, specify	8/48 (16.7%)	9	1/22 (4.5%)	1
Tooth infection	4/48 (8.3%)	4	1/22 (4.5%)	1
Urinary tract infection	3/48 (6.3%)	5	0/22 (0%)	0
Investigations
Alanine aminotransferase increased	15/48 (31.3%)	16	7/22 (31.8%)	8
Aspartate aminotransferase increased	12/48 (25%)	12	4/22 (18.2%)	4
Blood bilirubin increased	3/48 (6.3%)	3	2/22 (9.1%)	2
GGT increased	3/48 (6.3%)	8	3/22 (13.6%)	3
Investigations - Other, specify	6/48 (12.5%)	8	0/22 (0%)	0
Neutrophil count decreased	4/48 (8.3%)	5	10/22 (45.5%)	14
Platelet count decreased	5/48 (10.4%)	6	0/22 (0%)	0
Weight loss	5/48 (10.4%)	6	2/22 (9.1%)	2
Metabolism and nutrition disorders
Anorexia	17/48 (35.4%)	21	5/22 (22.7%)	5
Hypomagnesemia	3/48 (6.3%)	3	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	13/48 (27.1%)	17	2/22 (9.1%)	2
Back pain	10/48 (20.8%)	11	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorder - Other, specify	6/48 (12.5%)	6	4/22 (18.2%)	7
Myalgia	8/48 (16.7%)	9	5/22 (22.7%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	6/48 (12.5%)	6	0/22 (0%)	0
Nervous system disorders
Dysesthesia	2/48 (4.2%)	2	2/22 (9.1%)	2
Dysgeusia	13/48 (27.1%)	13	1/22 (4.5%)	1
Headache	21/48 (43.8%)	32	4/22 (18.2%)	5
Nervous system disorders - Other, specify	0/48 (0%)	0	2/22 (9.1%)	2
Paresthesia	2/48 (4.2%)	2	6/22 (27.3%)	6
Psychiatric disorders
Anxiety	4/48 (8.3%)	4	1/22 (4.5%)	1
Insomnia	5/48 (10.4%)	6	1/22 (4.5%)	1
Psychiatric disorders - Other, specify	4/48 (8.3%)	4	0/22 (0%)	0
Reproductive system and breast disorders
Uterine hemorrhage	3/48 (6.3%)	4	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/48 (8.3%)	4	0/22 (0%)	0
Epistaxis	4/48 (8.3%)	4	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, specify	3/48 (6.3%)	3	0/22 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	6/48 (12.5%)	6	4/22 (18.2%)	4
Dry skin	7/48 (14.6%)	8	0/22 (0%)	0
Palmar-plantar erythrodysesthesia syndrome	16/48 (33.3%)	22	0/22 (0%)	0
Pruritus	4/48 (8.3%)	4	1/22 (4.5%)	2
Skin and subcutaneous tissue disorders - Other, specify	36/48 (75%)	50	3/22 (13.6%)	3
Skin hypopigmentation	10/48 (20.8%)	10	0/22 (0%)	0
Vascular disorders
Hot flashes	5/48 (10.4%)	5	0/22 (0%)	0
Hypertension	22/48 (45.8%)	27	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

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.