Trial Outcomes & Findings for Phase II Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma (NCT NCT01687673)

Last Updated: 2020-12-07

Results Overview

Median TTP will be calculated in months from date of first dose of protocol therapy to date of removal from study for progression, where progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of the target lesions (SLD), taking as reference the smallest sum of the SLD recorded since the treatment started and minimum 5 millimeter (mm) increase over the nadir, or the appearance of one or more new lesions for target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions . Kaplan-Meier methods will be used to summarize the primary endpoint

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

24 months

Results posted on

2020-12-07

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Overall Study STARTED	29
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Overall Study Physician Decision	1

Baseline Characteristics

Phase II Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=29 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Age, Continuous	61 years n=93 Participants
Sex: Female, Male Female	4 Participants n=93 Participants
Sex: Female, Male Male	25 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	10 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	18 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	29 participants n=93 Participants
Baseline Alpha-fetoprotein (AFP) < 400 nanograms per millilitre (ng/mL)	20 Participants n=93 Participants
Baseline Alpha-fetoprotein (AFP) >= 400 ng/mL	9 Participants n=93 Participants

PRIMARY outcome

Timeframe: 24 months

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Median Time to Progression (TTP)	3.7 months Interval 2.2 to 5.3

SECONDARY outcome

Timeframe: 24 months

Response Rate (RR) is defined as any patient whom has a documented complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Results will be reported by number of participants for each response type: CR or PR.

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Response Rate (RR) Complete Response	0 participants
Response Rate (RR) Partial Response	0 participants

SECONDARY outcome

Timeframe: 24 months

Median PFS will be calculated in months from date of first dose of protocol therapy to date of documented disease progression or death from any cause, where progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the SLD of target lesions, taking as reference the smallest sum of the SLD recorded since the treatment started and minimum 5 millimeter (mm) increase over the nadir, or the appearance of one or more new lesions for target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Kaplan-Meier methods will be used to summarize time-to-event outcomes.

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Median Progression Free Survival (PFS)	3.7 months Interval 2.2 to 5.3

SECONDARY outcome

Timeframe: 60 months

Median OS for all enrolled patients (intention-to-treat) will be calculated from date of first dose of protocol therapy until date of death, using chart review and/or follow up phone calls to determine date of death in patients after removal from study. The survival of patients still alive after 5 years of follow up post study discontinuation will be censored.

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Median Overall Survival (OS)	8.8 months Interval 6.8 to 14.8

SECONDARY outcome

Timeframe: 24 months

TTF will be measured from date of first dose of protocol therapy to date of study discontinuation for progression, death, or toxicity.

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Time to Treatment Failure (TTF)	3.1 months Interval 0.7 to 15.0

SECONDARY outcome

Timeframe: 24 months

Population: Only 21 patients had AFP response data available at time of best AFP response

In patients with baseline AFP \>= 20 ng/mL, AFP response will be measured by the percent change from baseline value to the value at the time of best AFP response. The number of participants with ≥ 50% decline from baseline will be measured.

Outcome measures

Outcome measures
Measure	Treatment n=21 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Number of Patients With a Demonstrated Alpha-fetoprotein (AFP) Response	10 Participants

SECONDARY outcome

Timeframe: 24 months

The number of patients whom required a dose reduction due to toxicity as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be reported

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Number of Patients Whom Required a Dose Reduction	13 Participants

SECONDARY outcome

Timeframe: 24 months

The number of patients whom required a treatment delay due to toxicity as classified by the CTCAE version 4.0 will be reported

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Number of Patients Whom Required a Treatment Delay	14 Participants

SECONDARY outcome

Timeframe: 24 months

The number of participants whom discontinued treatment due to toxicity as classified by the CTCAE version 4.0 will be reported

Outcome measures

Outcome measures
Measure	Treatment n=28 Participants Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Number of Participants Whom Discontinued Treatment Due to Intolerable Toxicity	6 Participants

Adverse Events

Treatment

Serious events: 5 serious events

Other events: 20 other events

Deaths: 27 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=28 participants at risk Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Gastrointestinal disorders Abdominal pain	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Diarrhea	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Vomiting	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Infections and infestations Skin infection	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Dehydration	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Vascular disorders Thromboembolic event	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Blood and lymphatic system disorders Sepsis	3.6% 1/28 • Number of events 1 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.

Other adverse events

Other adverse events
Measure	Treatment n=28 participants at risk Combination temsirolimus plus sorafenib Temsirolimus: 10 mg weekly will be administered intravenously over 30 to 60 minutes using an infusion pump starting on Cycle 1, Day 1 of study enrollment. Sorafenib:: 200 mg tablet twice daily starting on Cycle 1, Day 1 of study enrollment after completion of temsirolimus infusion.
Metabolism and nutrition disorders Hypophosphatemia	60.7% 17/28 • Number of events 50 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Anorexia	21.4% 6/28 • Number of events 6 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Hypoalbuminemia	21.4% 6/28 • Number of events 12 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Hyperglycemia	17.9% 5/28 • Number of events 6 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Hypertriglyceridemia	14.3% 4/28 • Number of events 4 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Hypomagnesemia	14.3% 4/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Hypokalemia	10.7% 3/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Metabolism and nutrition disorders Dehydration	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Investigations Platelet count decreased	35.7% 10/28 • Number of events 22 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Investigations Weight loss	25.0% 7/28 • Number of events 11 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Investigations Blood bilirubin increased	10.7% 3/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Investigations Cholesterol high	10.7% 3/28 • Number of events 3 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Investigations Aspartate aminotransferase increased	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Investigations Neutrophil count decreased	7.1% 2/28 • Number of events 10 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Diarrhea	28.6% 8/28 • Number of events 11 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Abdominal pain	17.9% 5/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Dry mouth	17.9% 5/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Nausea	17.9% 5/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Constipation	14.3% 4/28 • Number of events 4 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Vomiting	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Ascites	7.1% 2/28 • Number of events 4 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Gastrointestinal disorders Mucositis oral	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
General disorders Fatigue	25.0% 7/28 • Number of events 8 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
General disorders Edema limbs	21.4% 6/28 • Number of events 7 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
General disorders Chills	10.7% 3/28 • Number of events 3 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
General disorders Infusion related reaction	10.7% 3/28 • Number of events 5 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
General disorders Fever	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Skin and subcutaneous tissue disorders Rash maculo-papular	28.6% 8/28 • Number of events 14 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	7.1% 2/28 • Number of events 3 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Skin and subcutaneous tissue disorders Dry skin	10.7% 3/28 • Number of events 3 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.7% 3/28 • Number of events 3 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Respiratory, thoracic and mediastinal disorders Hoarseness	10.7% 3/28 • Number of events 3 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Respiratory, thoracic and mediastinal disorders Pneumonitis	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Nervous system disorders Dysgeusia	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Renal and urinary disorders Urinary frequency	14.3% 4/28 • Number of events 4 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Blood and lymphatic system disorders Anemia	10.7% 3/28 • Number of events 10 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Infections and infestations Upper respiratory infection	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.
Psychiatric disorders Insomnia	7.1% 2/28 • Number of events 2 • Up to 60 months Only patients actively treated with a combination of Temsirolimus and Sorafenib were evaluated for safety.

Additional Information

Dr. R. Katie Kelley, MD

University of California, San Francisco

Phone: (415) 353-9888

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place