Trial Outcomes & Findings for Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma (NCT NCT02729194)

NCT ID: NCT02729194

Last Updated: 2019-06-10

Results Overview

Number of grade 3 or 4 adverse events associated with pazopanib administered with a low fat meal by CTCAE version 4.0.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: Through 12 weeks of treatment to 30 days post-treatment
• Results posted on: 2019-06-10

Participant Flow

Participant milestones

Measure	Pazopanib Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.
Overall Study STARTED	16
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Pazopanib Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Pilot Study of Pazopanib With Low Fat Meal (PALM) in Advanced Renal Cell Carcinoma

Baseline characteristics by cohort

Measure	Pazopanib n=16 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Baseline Performance Status 0	11 Participants n=5 Participants
Baseline Performance Status 1	5 Participants n=5 Participants
Histology Pure Clear Cell	11 Participants n=5 Participants
Histology Mixed Histology	5 Participants n=5 Participants
Baseline Disease Site Lung	10 Participants n=5 Participants
Baseline Disease Site Adrenal	6 Participants n=5 Participants
Baseline Disease Site Pancreas	1 Participants n=5 Participants
Baseline Disease Site Liver	3 Participants n=5 Participants
Baseline Disease Site Bone	1 Participants n=5 Participants
Baseline Disease Site Nephrectomy bed	2 Participants n=5 Participants
Baseline Disease Site Retroperitoneal and perisplenic nodule	1 Participants n=5 Participants
Heng Criteria Score Favorable	3 Participants n=5 Participants
Heng Criteria Score Intermediate	13 Participants n=5 Participants
Heng Criteria Score Poor	0 Participants n=5 Participants
Number of Prior Therapies No Prior Therapy	12 Participants n=5 Participants
Number of Prior Therapies 1 Prior Therapy	3 Participants n=5 Participants
Number of Prior Therapies 3 Prior Therapies	1 Participants n=5 Participants
Prior Therapy Type Everolimus	1 Participants n=5 Participants
Prior Therapy Type High-dose IL-2	3 Participants n=5 Participants
Prior Therapy Type Sunitinib	1 Participants n=5 Participants
Prior Therapy Type Nivolumab	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through 12 weeks of treatment to 30 days post-treatment

Population: 16 participants were enrolled and treated.

Number of grade 3 or 4 adverse events associated with pazopanib administered with a low fat meal by CTCAE version 4.0.

Outcome measures

Measure	Pazopanib n=16 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.
Number of Grade 3 or 4 Adverse Events Grade 3 adverse events associated with treatment	5 adverse events
Number of Grade 3 or 4 Adverse Events Grade 4 adverse events associated with treatment	0 adverse events

PRIMARY outcome

Timeframe: 12 weeks

Population: 16 participants were enrolled. 13 of the 16 enrolled participants completed the 12 weeks of pazopanib therapy on study protocol.

Outcome measures

Measure

Pazopanib n=13 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Number of Participants With Dose Reductions

3 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: 16 participants were enrolled. 13 of the 16 enrolled participants completed the 12 weeks of pazopanib therapy on study protocol.

The median duration of treatment will be reported.

Outcome measures

Measure

Pazopanib n=13 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Duration of Treatment

12 weeks Interval 1.0 to 12.0

PRIMARY outcome

Timeframe: 12 weeks

Population: 16 participants were enrolled. 13 of the 16 enrolled participants completed the 12 weeks of pazopanib therapy on study protocol.

Median total dose given.

Outcome measures

Measure

Pazopanib n=13 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Median Total Dose

42,700 mg Interval 1200.0 to

SECONDARY outcome

Timeframe: 12 Weeks after start of study treatment

Population: 16 participants were enrolled. 13 of the 16 enrolled participants completed the 12 weeks of pazopanib therapy on study protocol.

To estimate the overall response proportion to pazopanib administered with a low fat meal by RECIST 1.1 criteria. Overall response is defined as the number patients that experience Partial Response (PR) or Complete Response (CR).

CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.

PR is defined as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.

Outcome measures

Measure

Pazopanib n=13 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Percentage of Patients That Respond to Treatment (Overall Response) With Pazopanib Administered Along With a Low Fat Diet

38.46 percentage of participants Interval 11.0 to 59.0

SECONDARY outcome

Timeframe: 12 Weeks after start of study treatment

Population: 16 participants were enrolled. 13 of the 16 enrolled participants completed the 12 weeks of pazopanib therapy on study protocol.

Complete response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.

Outcome measures

Measure

Pazopanib n=13 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Number of Participants With Complete Response

0 Participants

SECONDARY outcome

Timeframe: 12 Weeks after start of study treatment

Population: 16 participants were enrolled. 13 of the 16 enrolled participants completed the 12 weeks of pazopanib therapy on study protocol.

Partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.

Outcome measures

Measure

Pazopanib n=13 Participants Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Number of Patients With Partial Response

5 Participants

Adverse Events

Pazopanib

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure

Pazopanib n=16 participants at risk Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.

Vascular disorders Hypertension

6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.

Other adverse events

Measure	Pazopanib n=16 participants at risk Registered subjects will take pazopanib by mouth with a low-fat meal (containing less than 400 calories and less than 10% fat or 10 grams per meal) every day in 14 day cycles, with a starting dose of 400 mg and adjusted for the next cycle (dose level +1:600 mg; dose level +2: 800 mg; dose level -1: 200 mg) based on toxicity assessment during or at the end of each cycle.
Blood and lymphatic system disorders Anemia	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Cardiac disorders Chest pain - cardiac	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Cardiac disorders Sick sinus syndrome	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Ear and labyrinth disorders Middle ear inflammation	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Endocrine disorders Endocrine disorders - Other	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Endocrine disorders Hyperthyroidism	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Endocrine disorders Hypothyroidism	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Eye disorders Blurred vision	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Abdominal pain	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Constipation	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Diarrhea	62.5% 10/16 • Number of events 12 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Flatulence	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Gastroesophageal reflux disease	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Mucositis oral	25.0% 4/16 • Number of events 4 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Nausea	50.0% 8/16 • Number of events 8 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Oral pain	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Gastrointestinal disorders Vomiting	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
General disorders Fatigue	43.8% 7/16 • Number of events 7 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
General disorders Pain	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Injury, poisoning and procedural complications Wound complication	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Alanine aminotransferase increased	68.8% 11/16 • Number of events 13 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Alkaline phosphatase increased	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Aspartate aminotransferase increased	75.0% 12/16 • Number of events 15 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Blood bilirubin increased	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Creatinine increased	18.8% 3/16 • Number of events 3 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Electrocardiogram QT corrected interval prolonged	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Lymphocyte count decreased	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Neutrophil count decreased	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Platelet count decreased	31.2% 5/16 • Number of events 7 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations Weight loss	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Investigations White blood cell decreased	31.2% 5/16 • Number of events 6 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Metabolism and nutrition disorders Anorexia	12.5% 2/16 • Number of events 3 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Metabolism and nutrition disorders Hyperglycemia	50.0% 8/16 • Number of events 16 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Metabolism and nutrition disorders Hyperkalemia	31.2% 5/16 • Number of events 5 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Metabolism and nutrition disorders Hypoglycemia	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Metabolism and nutrition disorders Hyponatremia	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Nervous system disorders Dysgeusia	18.8% 3/16 • Number of events 4 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Psychiatric disorders Insomnia	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Renal and urinary disorders Chronic kidney disease	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Alopecia	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Hypertrichosis	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Nail discoloration	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	12.5% 2/16 • Number of events 2 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Pruritus	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Rash acneiform	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Rash maculo-papular	12.5% 2/16 • Number of events 3 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Skin and subcutaneous tissue disorders Skin hypopigmentation	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Vascular disorders Hypertension	56.2% 9/16 • Number of events 10 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.
Vascular disorders Hypotension	6.2% 1/16 • Number of events 1 • Through 12 weeks of treatment up to 30 days post last treatment administration Adverse Events (AEs) were collected beginning at treatment start through 30 days post last treatment administration.

Additional Information

Dr. Ajjai Alva, M.D.

University of Michigan Rogel Cancer Center

Phone: 734-936-0091

Email: ajjai@umich.edu

Results disclosure agreements

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