Pazopanib in Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors (GIST)

• Sponsor: Kristen Ganjoo (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01391611
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 25
• Locations: 2
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study is being done to gather information about the safety (any harmful effects) and effectiveness (usefulness) of Pazopanib in the treatment of Gastrointestinal Stroma Tumors (GIST) that cannot be treated by surgery or has spread to other organs. The Food and Drug Administration (FDA) have approved Pazopanib for the treatment of advanced kidney cancer but it is not approved for the treatment of GIST. The investigators hope to learn about the safety and usefulness (effectiveness) of Pazopanib for patients with GIST.

Primary Objective:

Non-progression rate based on RECIST criteria (CR+PR+SD)

Secondary Objectives:

• Response per Choi criteria

• 6 month progression-free survival

• Safety and tolerability

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumor (GIST)	Drug: Pazopanib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Pazopanib in Patients With Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors (GIST)
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pazopanib arm	Drug: Pazopanib; 800 mg; PO; Other Names: Votrient

Outcome Measures

Primary Outcome Measures

1. Non-progression Rate Based on RECIST 1.0 Criteria (CR+PR+SD) [24 weeks]

   4-mo non-progression rate "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

Secondary Outcome Measures

1. Response Per Choi Criteria [6 months]

   Response per Choi criteria Complete response - Disappearance of all lesions; no new lesion Partial response - A decrease in size of > or = 10% or a decrease in tumor density (HU) > or = 15% on CT. No new lesions. No obvious progression of nonmeasurable disease. Stable disease - Does not meet the criteria for CR, PR, or PD. No symptomatic deterioration attributed to tumor progression. Progressive disease - An increase in tumor size of > or = 10% and does not meet criteria of PR by tumor density (HU) on CT. New lesions. New intratumoral nodules or increase in the size of the existing intratumoral nodules.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Metastatic or unresectable gastrointestinal stromal tumor (GIST)

• Failure or intolerance to Imatinib and sunitinib

• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.

• Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Measurable disease criteria by RECIST criteria

• Adequate organ system function as defined in protocol.

• A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant).

This includes any female who has had:

• A hysterectomy

• A bilateral oophorectomy (ovariectomy)

• A bilateral tubal ligation

• Menopause

• Childbearing potential females must have a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agree to use adequate contraception. Adequate acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

• An intrauterine device with a documented failure rate of less than 1% per year.

• Vasectomized partner who is sterile prior to the female subject?s entry and is the sole sexual partner for that female.

• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.

Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide edify eligible disease(s)/stage(s)

Exclusion Criteria:

• History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, early-stage bladder cancer, or low-grade endometrial cancer

• Clinically significant gastrointestinal abnormalities that may affect absorption of the investigational product

• Presence of uncontrolled infection

• Prolongation of corrected QT interval (QTc) > 480 milliseconds. On antiarrhythmics or medications known to prolong QT interval

• History of any one or more of the following cardiovascular conditions within the past 6 months:

• Cardiac angioplasty or stenting

• Myocardial infarction

• Unstable angina

• Coronary artery by-pass graft surgery

• Symptomatic peripheral vascular disease

• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)

• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg].

• History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months

• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture

• Evidence of active bleeding or bleeding diathesis.

• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to procedures.

• Patients on strong CYP3A4 inhibitors

• Uncorrected abnormal electrolytes- K, Mg and Ca

• Treatment with any of the following anti-cancer therapies:

• o radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR

• o chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Kristen Ganjoo
• GlaxoSmithKline

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: NCT01391611
• Other Study ID Numbers: IRB-20636; RR2002/00017/09; 11-311; GIST0003
• First Posted: Jul 12, 2011
• Last Update Posted: Apr 7, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors

Study Results

Participant Flow

Arm/Group Title	Pazopanib Arm
Arm/Group Description	Pazopanib: 800 mg; PO
Period Title: Overall Study
STARTED	25
COMPLETED	3
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	Pazopanib Arm
Arm/Group Description	Pazopanib: 800 mg; PO
Overall Participants	25
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	10 40%
Male	15 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4%
Not Hispanic or Latino	22 88%
Unknown or Not Reported	2 8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 12%
White	18 72%
More than one race	0 0%
Unknown or Not Reported	3 12%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Non-progression Rate Based on RECIST 1.0 Criteria (CR+PR+SD)
Description	4-mo non-progression rate "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pazopanib Arm
Arm/Group Description	Pazopanib: 800 mg; PO
Measure Participants	25
Median (95% Confidence Interval) [months]	1.9

2. Secondary Outcome

Title	Response Per Choi Criteria
Description	Response per Choi criteria Complete response - Disappearance of all lesions; no new lesion Partial response - A decrease in size of > or = 10% or a decrease in tumor density (HU) > or = 15% on CT. No new lesions. No obvious progression of nonmeasurable disease. Stable disease - Does not meet the criteria for CR, PR, or PD. No symptomatic deterioration attributed to tumor progression. Progressive disease - An increase in tumor size of > or = 10% and does not meet criteria of PR by tumor density (HU) on CT. New lesions. New intratumoral nodules or increase in the size of the existing intratumoral nodules.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Choi criteria measurements were not done due to technical difficulties.

Arm/Group Title	Pazopanib Arm
Arm/Group Description	Pazopanib: 800 mg; PO
Measure Participants	0
	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. These were captured every months at clinic visit and patients also could report in between visits.
Adverse Event Reporting Description	Patients were asked about adverse events at every clinic visit.
Arm/Group Title	Pazopanib Arm
Arm/Group Description	Pazopanib: 800 mg; PO
All Cause Mortality
	Pazopanib Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pazopanib Arm
	Affected / at Risk (%)	# Events
Total	14/25 (56%)
Blood and lymphatic system disorders
Anemia G2	1/25 (4%)	1
Gastrointestinal disorders
Worsened ascites G1	1/25 (4%)	1
Constipation G2	1/25 (4%)	1
GI disorders-other, E. coli bacteremia G3	1/25 (4%)	1
Intestinal perforation G4	1/25 (4%)	1
Ascites G3	2/25 (8%)	2
Abdominal pain G3	2/25 (8%)	4
GI Bleed G3	2/25 (8%)	2
Rectal hemorrhage, rectum bleeding	1/25 (4%)	1
GI Bleed G5	1/25 (4%)	1
Acute pancreatitis G3	1/25 (4%)	1
General disorders
General disorders and administration site conditions-other, specify, Disease progression-fatal G5	1/25 (4%)	1
Fatigue G2	1/25 (4%)	1
Worsening fatigue G3	1/25 (4%)	1
Hepatobiliary disorders
Nonviral hepatitis/transaminitis G2	1/25 (4%)	1
Investigations
Blood bilirubin increased G3	1/25 (4%)	1
Alkaline phosphatase increased G3	1/25 (4%)	1
AST incresed G3	1/25 (4%)	1
ALT increased G3	1/25 (4%)	1
GGT increased G3	1/25 (4%)	1
Metabolism and nutrition disorders
Hypoalbuminemia G3	1/25 (4%)	1
Dehydration G3	1/25 (4%)	1
Nervous system disorders
Peripheral motor neuropathy G2	1/25 (4%)	1
Seizure G3	1/25 (4%)	1
Cognitive disturbance G2	1/25 (4%)	1
Renal and urinary disorders
Renal failure G5	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Worsened shortness of breath	1/25 (4%)	1
Pulmonary embolism G3	1/25 (4%)	1
Pneumonia G1	1/25 (4%)	1
Worsened right pleural effusion G1	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Sacral decubitus G1	1/25 (4%)	1
Vascular disorders
Deep venous thrombosis G1	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Pazopanib Arm
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Worsened anemia G1	2/25 (8%)	2
Worsened anemia G2	1/25 (4%)	1
Worsening anemia G3	1/25 (4%)	1
Anemia (secondary to GI bleed) G3	1/25 (4%)	1
Neutropenia G2	2/25 (8%)	3
Leukopenia G2	1/25 (4%)	1
Leukopenia G1	1/25 (4%)	1
Thrombocytopenia G1	1/25 (4%)	1
Endocrine disorders
Hypothyroidism G2	1/25 (4%)	1
Gastrointestinal disorders
Vomiting G1	6/25 (24%)	6
Intermittent vomiting G1	4/25 (16%)	4
Vomiting G2	1/25 (4%)	1
Vomiting G3	1/25 (4%)	1
Intermittent nausea G1	3/25 (12%)	3
Nausea G1	6/25 (24%)	7
Nausea G2	1/25 (4%)	1
Nausea G3	1/25 (4%)	1
Intermittent worsened abdominal pain w/ radiation to R shoulder G2	1/25 (4%)	1
Intermittent diarrhea G1	2/25 (8%)	2
Diarrhea G1	9/25 (36%)	9
Intermittent constipation G1	2/25 (8%)	2
Constipation G2	1/25 (4%)	1
Intermittent cramps abdomen G1	1/25 (4%)	1
Early satiety G1	3/25 (12%)	3
Hemorrhoids G1	1/25 (4%)	1
Constipation G1	2/25 (8%)	2
Abdominal cramping G2	1/25 (4%)	1
Intermittent postprandial cramping G1	1/25 (4%)	1
Intermittent abdominal pain G1	1/25 (4%)	1
Abdominal pain G1	4/25 (16%)	4
Left lower abdominal and lower back pain	1/25 (4%)	1
Abdominal pain G2	5/25 (20%)	6
Worsened LUQ pain G3	1/25 (4%)	1
Axorexia G2	1/25 (4%)	1
Intermittent sore mouth G1	1/25 (4%)	1
Mouth pain G1	3/25 (12%)	3
Oral dysesthesia G1	1/25 (4%)	1
Dysgeusia G1	1/25 (4%)	1
Ascites G3	1/25 (4%)	1
Retching G1	1/25 (4%)	1
Bloating G1	1/25 (4%)	1
General disorders
Fatigue G1	5/25 (20%)	7
Fatigue G2	8/25 (32%)	8
Intermittent night sweats G1	2/25 (8%)	2
Weight loss G1	2/25 (8%)	2
Fever G1	1/25 (4%)	1
Pain G2	2/25 (8%)	2
Drowsiness G1	1/25 (4%)	1
Dehydration G3	1/25 (4%)	1
Lightheadedness G1	1/25 (4%)	1
Dizziness G1	1/25 (4%)	1
Infections and infestations
Thrush (mucosal infection) G1	1/25 (4%)	1
oral candidiasis G2	1/25 (4%)	1
Investigations
Blood bilirubin increased G1	2/25 (8%)	2
Blood bilirubin increased G2	1/25 (4%)	1
Alkaline phosphatase increased G1	1/25 (4%)	1
GGT increased G1	1/25 (4%)	1
ALT increased G1	1/25 (4%)	1
AST increased G1	2/25 (8%)	2
AST increased G2	1/25 (4%)	1
Alkaline phosphatase increased G2	1/25 (4%)	1
GGT increased G2	1/25 (4%)	1
Metabolism and nutrition disorders
Hyperkalemia G2	1/25 (4%)	1
Decreased appetite G1	2/25 (8%)	2
Decreased appetite G2	1/25 (4%)	1
Anorexia G1	2/25 (8%)	2
Hypomagnesemia G1	3/25 (12%)	3
Hypoalbuminemia G2	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Worsened back pain G1	1/25 (4%)	1
Jaw pain right G1	1/25 (4%)	1
Bilateral femur pain	1/25 (4%)	1
Intermittent back pain G1	2/25 (8%)	2
Worsened low back pain with radiation to buttocks, R hip G2	1/25 (4%)	1
Acute lower back pain G2	1/25 (4%)	1
Intermittent cramps, feet	1/25 (4%)	1
Intermittent pain/cramps legs G1	1/25 (4%)	1
Pain elbow G1	1/25 (4%)	1
Decreased strength G1	1/25 (4%)	1
Weakness lower extremities G2	1/25 (4%)	1
Generalized weakness G1	1/25 (4%)	1
Pain B/L legs R>L G1	1/25 (4%)	1
Joint and muscle pain G1	1/25 (4%)	1
Intermittent right shoulder pain G1	1/25 (4%)	1
Worsening pain G1	1/25 (4%)	1
Left wrist pain with cellulitis	1/25 (4%)	1
Lower back and left calf pain G2	1/25 (4%)	1
Intermittent leg cramps G1	2/25 (8%)	2
Leg cramps (pain) G2	1/25 (4%)	1
Muscle weakness G1	1/25 (4%)	1
Left ankle weakness G2	1/25 (4%)	1
Nervous system disorders
Loss of consciousness, transient G1	1/25 (4%)	1
Headache G1	6/25 (24%)	6
Headache G3	1/25 (4%)	1
Psychiatric disorders
Anxiety G1	1/25 (4%)	1
Insomnia G1	1/25 (4%)	1
Renal and urinary disorders
Urinary tract infection G1	1/25 (4%)	1
Decreased urine output	1/25 (4%)	1
Cystitis G1	1/25 (4%)	1
Proteinuria G2	1/25 (4%)	1
Proteinuria G3	1/25 (4%)	1
Elevated UPC G1	1/25 (4%)	1
Reproductive system and breast disorders
Vaginal bleeding G1	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of breath G1	2/25 (8%)	2
Worsened DOE G1	1/25 (4%)	2
Dyspnea G1	2/25 (8%)	2
Upper respiratory symptoms G1	1/25 (4%)	1
Epistaxis G1	3/25 (12%)	3
Rhinorrhea and throat discomfort	1/25 (4%)	1
Cough G1	1/25 (4%)	1
Epistaxis G2	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Facial flushing G1	1/25 (4%)	1
Generalized depigmentation G2	1/25 (4%)	1
Hand/foot syndrome	3/25 (12%)	3
Rash G1	3/25 (12%)	3
Facial and hand edema G1	1/25 (4%)	1
Infection - rash G2	1/25 (4%)	1
Skin irritation - perianal G1	1/25 (4%)	1
Hypopigmentation B/L forearms G1	1/25 (4%)	1
Skin dryness G1	2/25 (8%)	2
Whitening of hair G1	1/25 (4%)	1
Pruritus G1	1/25 (4%)	1
Hair lightening G2	1/25 (4%)	1
Vascular disorders
Hypertension G1	1/25 (4%)	1
Hypertension G2	6/25 (24%)	7
Hypertension G3	3/25 (12%)	4
Hypotension G3	1/25 (4%)	1

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.