Trial Outcomes & Findings for Sutent and Radiation as Treatment for Limited Extent Metastatic Cancer (NCT NCT00463060)

Last Updated: 2018-07-18

Results Overview

Sunitinib (SU) and radiation (IGRT) doses were sequentially escalated using a ping-pong strategy according to a 3 + 3 design phase 1 study. The starting dose was sunitinib 25 mg and IGRT 40 Gy. MTD reflects the highest dose that did not cause a dose limiting toxicity. Toxicity was in assessed in patients at regular intervals by using the Common Terminology Criteria for Adverse Events criteria (version 3.0). Dose limiting events were defined as any grade 4 or 5 toxicity and unexpected grade 3 toxicity. Expected grade 3 toxicities from radiation include mucositis or esophagitis lasting ≤7 days. Grade 3 metabolic and hematologic toxicities are considered expected events with sunitinib and therefore were not considered DLTs

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

47 participants

Primary outcome timeframe

2 years

Results posted on

2018-07-18

Participant Flow

Recruitment period began January 2007 and was open for recruitment through July 2014 with 47 patients enrolled in the study between February 2007 and September 2010.

One patient withdrew prior to starting treatment and was excluded from analysis. Phase 1: 21 patients in Phase 1 in dose-escalating study to find maximum-tolerated dose Phase 2: 25 patients on the recommended phase II dose, 37.5mg

Participant milestones

Participant milestones
Measure	Advanced Solid Tumor Malignancy Patients were eligible if they had histologically or cytological documented advanced solid tumor malignancy with radiographic evidence of 1 to 5 sites of active metastatic disease.
Phase 1-Radiation 40 Gy + Sunitinib 25mg STARTED	3
Phase 1-Radiation 40 Gy + Sunitinib 25mg COMPLETED	3
Phase 1-Radiation 40 Gy + Sunitinib 25mg NOT COMPLETED	0
Phase 1-Radiation 40 Gy+Sunitinib 37.5mg STARTED	3
Phase 1-Radiation 40 Gy+Sunitinib 37.5mg COMPLETED	3
Phase 1-Radiation 40 Gy+Sunitinib 37.5mg NOT COMPLETED	0
Phase 1-Radiation 50 Gy+Sunitinib 37.5mg STARTED	10
Phase 1-Radiation 50 Gy+Sunitinib 37.5mg COMPLETED	10
Phase 1-Radiation 50 Gy+Sunitinib 37.5mg NOT COMPLETED	0
Phase 1-Radiation 50Gy +Sunitinib 50mg STARTED	5
Phase 1-Radiation 50Gy +Sunitinib 50mg COMPLETED	0
Phase 1-Radiation 50Gy +Sunitinib 50mg NOT COMPLETED	5
Phase 2-Radiation 50Gy +Sunitinib 37.5mg STARTED	26
Phase 2-Radiation 50Gy +Sunitinib 37.5mg COMPLETED	25
Phase 2-Radiation 50Gy +Sunitinib 37.5mg NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Advanced Solid Tumor Malignancy Patients were eligible if they had histologically or cytological documented advanced solid tumor malignancy with radiographic evidence of 1 to 5 sites of active metastatic disease.
Phase 1-Radiation 50Gy +Sunitinib 50mg acute toxicity	5
Phase 2-Radiation 50Gy +Sunitinib 37.5mg Withdrawal by Subject	1

Baseline Characteristics

Sutent and Radiation as Treatment for Limited Extent Metastatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=21 Participants N=21 participants Patients enrolled between Feb 2007 and May 2008	Phase II Advanced Solid Tumor Malignancy n=25 Participants Patients were eligible if they had histologically or cytological documented advanced solid tumor malignancy with radiographic evidence of 1 to 5 sites of active metastatic disease. N=26 participants Patients enrolled between February 2008 and September 2010	Total n=46 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	63 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
ECOG Performance status 0	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants
ECOG Performance status 1	9 participants n=5 Participants	13 participants n=7 Participants	22 participants n=5 Participants
ECOG Performance status 2	5 participants n=5 Participants	8 participants n=7 Participants	13 participants n=5 Participants
Prior systemic chemotherapy Yes	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Prior systemic chemotherapy No	8 participants n=5 Participants	14 participants n=7 Participants	22 participants n=5 Participants
Prior radiation therapy Yes	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Prior radiation therapy No	10 participants n=5 Participants	15 participants n=7 Participants	25 participants n=5 Participants
Number of metastases 1	13 participants n=5 Participants	13 participants n=7 Participants	26 participants n=5 Participants
Number of metastases 2	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Number of metastases >=3	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Largest Tumor size <=3cm	11 participants n=5 Participants	15 participants n=7 Participants	26 participants n=5 Participants
Largest Tumor size >=3cm	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Number of involved organs 1	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
Number of involved organs >=2	4 participants n=5 Participants	11 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Phase 1 - Radiation 40Gy + Sunitinib 25 mg n=3 Participants	Phase 1 - Radiation 40Gy + Suniitnib 37.5 mg n=3 Participants	Phase 1 - Radiation 50Gy + Sunitinib 37.5mg n=10 Participants	Phase 1 - Radiation 50Gy + Sunitinib 50mg n=5 Participants
Number of Participants With Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: 5 years

Population: Phase 2 only

Number of participants who have no evidence of disease and number of participants with distant metastases.

Outcome measures

Outcome measures
Measure	Phase 1 - Radiation 40Gy + Sunitinib 25 mg n=46 Participants	Phase 1 - Radiation 40Gy + Suniitnib 37.5 mg	Phase 1 - Radiation 50Gy + Sunitinib 37.5mg	Phase 1 - Radiation 50Gy + Sunitinib 50mg
Number of Participants With Particular Disease Status No evidence of disease	12 participants	—	—	—
Number of Participants With Particular Disease Status distant metastases	3 participants	—	—	—

SECONDARY outcome

Timeframe: 5 years

% of patients experienced one or more grade ≥ 3 toxicities. Toxicity is graded as mild (Grade 1), moderate (Grade 2), severe (Grade 3), or life-threatening (Grade 4),and death (Grade 5).

Outcome measures

Outcome measures
Measure	Phase 1 - Radiation 40Gy + Sunitinib 25 mg n=46 Participants	Phase 1 - Radiation 40Gy + Suniitnib 37.5 mg	Phase 1 - Radiation 50Gy + Sunitinib 37.5mg	Phase 1 - Radiation 50Gy + Sunitinib 50mg
Percentage of Patients With Toxicity Grade 3 or Higher	15 Participants	—	—	—

SECONDARY outcome

Timeframe: 4 years

Population: the 4-year estimates for local control

Local control was defined as a tumor volume equal to or less than the tumor volume at start of radiotherapy.

Outcome measures

Outcome measures
Measure	Phase 1 - Radiation 40Gy + Sunitinib 25 mg n=46 Participants	Phase 1 - Radiation 40Gy + Suniitnib 37.5 mg	Phase 1 - Radiation 50Gy + Sunitinib 37.5mg	Phase 1 - Radiation 50Gy + Sunitinib 50mg
Percentage of Patients With Local Control	75 percentage of participants Interval 55.0 to 87.0	—	—	—

SECONDARY outcome

Timeframe: 4 weeks

Distant control defined as distant metastasis contained outside of the radiation field within months of treatment.

Outcome measures

Outcome measures
Measure	Phase 1 - Radiation 40Gy + Sunitinib 25 mg n=46 Participants	Phase 1 - Radiation 40Gy + Suniitnib 37.5 mg	Phase 1 - Radiation 50Gy + Sunitinib 37.5mg	Phase 1 - Radiation 50Gy + Sunitinib 50mg
Percentage of Patients With Distant Control	40 percentage of participants Interval 24.0 to 55.0	—	—	—

SECONDARY outcome

Timeframe: 4-6 weeks after radiation therapy

Population: data not collected

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 years

Outcome measures

Outcome measures
Measure	Phase 1 - Radiation 40Gy + Sunitinib 25 mg n=46 Participants	Phase 1 - Radiation 40Gy + Suniitnib 37.5 mg	Phase 1 - Radiation 50Gy + Sunitinib 37.5mg	Phase 1 - Radiation 50Gy + Sunitinib 50mg
Number of Participants According Failure and Survival dead from comorbid illness	6 Participants	—	—	—
Number of Participants According Failure and Survival dead from treatment-related toxicities	2 Participants	—	—	—
Number of Participants According Failure and Survival alive with distant metastases	3 Participants	—	—	—
Number of Participants According Failure and Survival dead from distant metasteses	22 Participants	—	—	—
Number of Participants According Failure and Survival dead from local progression	1 Participants	—	—	—
Number of Participants According Failure and Survival alive without evidence of disease	12 Participants	—	—	—

Adverse Events

Phase 1

Serious events: 13 serious events

Other events: 21 other events

Deaths: 13 deaths

Phase 2

Serious events: 13 serious events

Other events: 26 other events

Deaths: 18 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1 n=21 participants at risk N=21 participants Patients enrolled between Feb 2007 and May 2008	Phase 2 n=26 participants at risk Patients were eligible if they had histologically or cytological documented advanced solid tumor malignancy with radiographic evidence of 1 to 5 sites of active metastatic disease. N=26 participants Patients enrolled between February 2008 and September 2010
Blood and lymphatic system disorders Anemia	4.8% 1/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	7.7% 2/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Immune system disorders Neutropenia	19.0% 4/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	7.7% 2/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Hepatobiliary disorders LFT abnormalities	14.3% 3/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	3.8% 1/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Immune system disorders Thrombocytopenia	14.3% 3/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	15.4% 4/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Blood and lymphatic system disorders Bleeding	4.8% 1/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	7.7% 2/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Endocrine disorders Metabolic abnormalities	9.5% 2/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	3.8% 1/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Renal and urinary disorders Increased creatinine	0.00% 0/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	3.8% 1/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
General disorders Nausea/vomiting	4.8% 1/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	0.00% 0/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Blood and lymphatic system disorders Lymphopenia	61.9% 13/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	0.00% 0/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.

Other adverse events

Additional Information

Dr. Johnny Kao

Good Samaritan Hospital Medical Center

Phone: (631) 376-4444

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase 1 n=21 participants at risk N=21 participants Patients enrolled between Feb 2007 and May 2008	Phase 2 n=26 participants at risk Patients were eligible if they had histologically or cytological documented advanced solid tumor malignancy with radiographic evidence of 1 to 5 sites of active metastatic disease. N=26 participants Patients enrolled between February 2008 and September 2010
Blood and lymphatic system disorders Anemia	66.7% 14/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	61.5% 16/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Blood and lymphatic system disorders Neutropenia	57.1% 12/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	46.2% 12/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
General disorders Fatigue	61.9% 13/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	69.2% 18/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Hepatobiliary disorders LFT abnormalities	38.1% 8/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	53.8% 14/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Blood and lymphatic system disorders Thrombocytopenia	33.3% 7/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	42.3% 11/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Infections and infestations Mucositis/stomatitis	33.3% 7/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	30.8% 8/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
General disorders Nausea/vomiting	28.6% 6/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	26.9% 7/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Skin and subcutaneous tissue disorders Skin changes	19.0% 4/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	15.4% 4/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Gastrointestinal disorders Diarrhea	14.3% 3/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	19.2% 5/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Cardiac disorders Hypertension	14.3% 3/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	11.5% 3/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Blood and lymphatic system disorders Bleeding	0.00% 0/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	7.7% 2/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Metabolism and nutrition disorders Metabolic abnormalities	14.3% 3/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	3.8% 1/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Renal and urinary disorders Increased creatinine	0.00% 0/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	19.2% 5/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Infections and infestations Hand foot syndrome	9.5% 2/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	0.00% 0/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Metabolism and nutrition disorders Hypothryrodism	0.00% 0/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	3.8% 1/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.
Blood and lymphatic system disorders Lymphopenia	4.8% 1/21 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.	0.00% 0/26 • Patients from Phase I and patients from Phase II, various doses of sunitinib (25mg to 50mg) and radiotherapy (40 to 50Gy). Median follow up was 3.6 years. Patients were followed until death.