Trial Outcomes & Findings for Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients With Soft Tissue Sarcoma of the Extremity and Body Wall (NCT NCT00864032)

Results Overview

Number of dose limiting toxicities and number with adverse events. Dose-escalation schedule comprising 6 to 12 patients (see schema). This sample size is based on a traditional 3+3 cohort design with escalating doses of sorafenib in combination with 50 Gy of conformal radiotherapy delivered in 25 fractions (200 cGy per fraction). Based on preclinical data regarding the radiobiology of sorafenib,33, 36 sorafenib will be initiated at a dose of 200 mg twice daily, followed by 200 mg Q AM/400 mg Q PM for the 2nd cohort, followed by 400 mg bid for the 3rd cohort. Since 400 mg bid is the well established MTD for sorafenib monotherapy in patients with renal cell carcinoma and hepatocellular carcinoma, the dose will not be escalated above this level even if DLT is not observed. Dose level escalation will be determined based on DLTs observed from initiation of sorafenib/RT until time of surgery.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Approximately 12 weeks

Results posted on

2013-04-10

Participant Flow

Participant milestones

Participant milestones
Measure	Sorafenib 200/200 Dose level 1 sorafenib 200 bid with concurrent neoadjuvant radiation therapy. sorafenib administered orally. agent administered during concurrent neoadjuvant radiation therapy. both modalities discontinued approximately 4 - 6 weeks prior to surgical resection with curative intent.	Sorafenib 200/400 Dose level 2 sorafenib 200 mg PO Q AM and 400 mg PO Q PM with concurrent neoadjuvant radiation therapy. sorafenib administered orally. agent administered during concurrent neoadjuvant radiation therapy. both modalities discontinued approximately 4 - 6 weeks prior to surgical resection with curative intent. Traditional 3+3 dose escalation Phase I trial. Cohort 2 enrolled after completion of all 3 participants in dose level 1.
Overall Study STARTED	3	5
Overall Study COMPLETED	3	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients With Soft Tissue Sarcoma of the Extremity and Body Wall

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=8 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age Continuous	44 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 12 weeks

Number of dose limiting toxicities and number with adverse events. Dose-escalation schedule comprising 6 to 12 patients (see schema). This sample size is based on a traditional 3+3 cohort design with escalating doses of sorafenib in combination with 50 Gy of conformal radiotherapy delivered in 25 fractions (200 cGy per fraction). Based on preclinical data regarding the radiobiology of sorafenib,33, 36 sorafenib will be initiated at a dose of 200 mg twice daily, followed by 200 mg Q AM/400 mg Q PM for the 2nd cohort, followed by 400 mg bid for the 3rd cohort. Since 400 mg bid is the well established MTD for sorafenib monotherapy in patients with renal cell carcinoma and hepatocellular carcinoma, the dose will not be escalated above this level even if DLT is not observed. Dose level escalation will be determined based on DLTs observed from initiation of sorafenib/RT until time of surgery.

Outcome measures

Outcome measures
Measure	Sorafenib 200/200 n=3 Participants	Sorafenib 200/400 n=5 Participants
Number of Dose Limiting Toxicities	0 DLTs	2 DLTs

Adverse Events

Sorafenib 200/200

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Sorafenib 200/400

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sorafenib 200/200 n=3 participants at risk Dose level 1. Sorafenib 200 mg PO BID	Sorafenib 200/400 n=5 participants at risk Dose level 2. Sorafenib 200 mg PO Q AM and 400 mg PO Q PM
Skin and subcutaneous tissue disorders rash	0.00% 0/3	40.0% 2/5 • Number of events 2

Other adverse events

Other adverse events
Measure	Sorafenib 200/200 n=3 participants at risk Dose level 1. Sorafenib 200 mg PO BID	Sorafenib 200/400 n=5 participants at risk Dose level 2. Sorafenib 200 mg PO Q AM and 400 mg PO Q PM
Skin and subcutaneous tissue disorders perirectal abscess	0.00% 0/3	20.0% 1/5 • Number of events 1
Blood and lymphatic system disorders anemia	0.00% 0/3	20.0% 1/5 • Number of events 1
Cardiac disorders Hypertension	33.3% 1/3 • Number of events 1	20.0% 1/5 • Number of events 1
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • Number of events 1	0.00% 0/5
Nervous system disorders Hand-Foot syndrome	33.3% 1/3 • Number of events 1	20.0% 1/5 • Number of events 1

Additional Information

Dr. Robert J. Canter

University of California Davis Comprehensive Cancer Center

Phone: 916-734-5907

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60