Trial Outcomes & Findings for Sorafenib With Either Temsirolimus or Tipifarnib in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed By Surgery (NCT NCT00281957)

NCT ID: NCT00281957

Last Updated: 2014-05-20

Results Overview

Complete response corresponds to complete disappearance of all measurable and non-measurable lesions with no new lesions. Partial response corresponds to greater than or equal to 30ﬁ decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

Every 8 weeks until progression

Results posted on

2014-05-20

Participant Flow

Participant milestones

Participant milestones
Measure	Sorafenib + Temsirolimus Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Sorafenib + Tipifarnib Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
Overall Study STARTED	67	42
Overall Study Eligible	66	40
Overall Study Eligible and Received Treatment	63	39
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	67	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Sorafenib + Temsirolimus Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Sorafenib + Tipifarnib Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
Overall Study Adverse Event	7	2
Overall Study Death	1	0
Overall Study Progression/relapse	47	35
Overall Study Not protocol specified	8	1
Overall Study Not eligible	1	2
Overall Study Did not start treatment	3	1
Overall Study Refusal unrelated to adverse events	0	1

Baseline Characteristics

Sorafenib With Either Temsirolimus or Tipifarnib in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed By Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I: Sorafenib + Temsirolimus n=63 Participants Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Arm II: Sorafenib + Tipifarnib n=39 Participants Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21	Total n=102 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	58 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	17 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	22 Participants n=7 Participants	56 Participants n=5 Participants
Region of Enrollment United States	63 participants n=5 Participants	39 participants n=7 Participants	102 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 8 weeks until progression

Outcome measures

Outcome measures
Measure	Sorafenib+Temsirolimus n=63 Participants Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Sorafenib+Tipifarnib n=39 Participants Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
Response Rate (Complete and Partial)	5 Percent of participants Interval 1.0 to 13.0	3 Percent of participants Interval 0.0 to 13.0

PRIMARY outcome

Timeframe: 4 months after registration

Progression was defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed, unequivocal progression of non-measurable disease, appearance of any new lesions, death due to disease without prior documentation of progression and without symptomatic deterioration.

Outcome measures

Outcome measures
Measure	Sorafenib+Temsirolimus n=63 Participants Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Sorafenib+Tipifarnib n=39 Participants Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
4-month Progression-free Survival	29 Percent of population Interval 19.0 to 41.0	18 Percent of population Interval 8.0 to 31.0

SECONDARY outcome

Timeframe: One year after registration

Outcome measures

Outcome measures
Measure	Sorafenib+Temsirolimus n=63 Participants Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Sorafenib+Tipifarnib n=39 Participants Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
One-year Overall Survival	19 Percent of population Interval 11.0 to 30.0	31 Percent of population Interval 17.0 to 45.0

SECONDARY outcome

Timeframe: Weekly during first cycle, every two weeks during the second cycle, and once a cycle further cycles (one cycle = 4 weeks).

Population: Eligible patients who had received any hydroxyurea

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Outcome measures

Outcome measures
Measure	Sorafenib+Temsirolimus n=63 Participants Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.	Sorafenib+Tipifarnib n=39 Participants Patients receive oral sorafenib as in arm I and oral tipifarnib twice daily on days 1-21
Toxicity Lipase	0 Participants	1 Participants
Toxicity Pancreatitis	1 Participants	1 Participants
Toxicity Thrombosis/thrombus/embolism	0 Participants	1 Participants
Toxicity ALT, SGPT (serum glutamic pyruvic transaminase)	0 Participants	1 Participants
Toxicity AST, SGOT (serum glut oxaloacetic transaminase)	0 Participants	1 Participants
Toxicity Amylase	0 Participants	1 Participants
Toxicity Anorexia	1 Participants	0 Participants
Toxicity Calcium, serum-low (hypocalcemia)	1 Participants	0 Participants
Toxicity Confusion	2 Participants	0 Participants
Toxicity Constitutional Symptoms-Other (Specify)	1 Participants	0 Participants
Toxicity Cough	1 Participants	0 Participants
Toxicity Creatinine	1 Participants	0 Participants
Toxicity Dehydration	3 Participants	0 Participants
Toxicity Dermatology/Skin-Other (Specify)	0 Participants	1 Participants
Toxicity Diarrhea	4 Participants	1 Participants
Toxicity Dyspnea (shortness of breath)	1 Participants	1 Participants
Toxicity Fatigue (asthenia, lethargy, malaise)	8 Participants	2 Participants
Toxicity Gastrointestinal-Other (Specify)	1 Participants	0 Participants
Toxicity Glucose, serum-high (hyperglycemia)	1 Participants	0 Participants
Toxicity Heartburn/dyspepsia	0 Participants	1 Participants
Toxicity Hemoglobin	2 Participants	0 Participants
Toxicity Hemorrhage, GI - Stomach	1 Participants	0 Participants
Toxicity Hypertension	1 Participants	2 Participants
Toxicity Hypotension	1 Participants	0 Participants
Toxicity Ileus, GI	1 Participants	0 Participants
Toxicity Infec with norm ANC or Gr 1/2 neut- Nose	1 Participants	0 Participants
Toxicity Infec with norm ANC or Gr 1/2 neut-Skin	1 Participants	0 Participants
Toxicity Left ventricular systolic dysfunction	1 Participants	0 Participants
Toxicity Lymphopenia	1 Participants	0 Participants
Toxicity Mood alteration - depression	0 Participants	1 Participants
Toxicity Mucositis/stomatitis (clinical exam) - Oral cavity	2 Participants	0 Participants
Toxicity Muscle weakness, gen or spec area-Extraocular	1 Participants	0 Participants
Toxicity Muscle weakness, gen or spec area-Whole body	2 Participants	1 Participants
Toxicity Nausea	3 Participants	0 Participants
Toxicity Neurology-Other (Specify)	1 Participants	0 Participants
Toxicity Neuropathy: motor	0 Participants	1 Participants
Toxicity Obstruction, GI - Small bowel NOS	1 Participants	0 Participants
Toxicity Pain - Abdomen NOS	1 Participants	2 Participants
Toxicity Pain - Back	1 Participants	2 Participants
Toxicity Pain - Chest wall	1 Participants	0 Participants
Toxicity Pain - Chest/thorax NOS	1 Participants	1 Participants
Toxicity Pain - Extremity-limb	1 Participants	1 Participants
Toxicity Pain - Head/headache	1 Participants	0 Participants
Toxicity Pain - Joint	1 Participants	1 Participants
Toxicity Pain - Muscle	1 Participants	0 Participants
Toxicity Pain - Neuralgia/peripheral nerve	0 Participants	1 Participants
Toxicity Pain - Oral cavity	1 Participants	0 Participants
Toxicity Pain - Pelvis	0 Participants	1 Participants
Toxicity Pain - Rectum	1 Participants	0 Participants
Toxicity Pain - Skin	1 Participants	0 Participants
Toxicity Pain - Stomach	1 Participants	0 Participants
Toxicity Phosphate, serum-low (hypophosphatemia)	8 Participants	1 Participants
Toxicity Platelets	1 Participants	0 Participants
Toxicity Pneumonitis/pulmonary infiltrates	2 Participants	0 Participants
Toxicity Potassium, serum-low (hypokalemia)	4 Participants	0 Participants
Toxicity Proteinuria	1 Participants	0 Participants
Toxicity Pruritus/itching	2 Participants	1 Participants
Toxicity Pulmonary/Upper Respiratory-Other (Specify)	1 Participants	0 Participants
Toxicity Rash/desquamation	4 Participants	2 Participants
Toxicity Rash: acne/acneiform	3 Participants	5 Participants
Toxicity Rash: erythema multiforme	1 Participants	0 Participants
Toxicity Rash: hand-foot skin reaction	2 Participants	4 Participants
Toxicity Renal failure	2 Participants	0 Participants
Toxicity Sodium, serum-low (hyponatremia)	1 Participants	0 Participants
Toxicity Vomiting	3 Participants	0 Participants

Adverse Events

Arm I

Serious events: 13 serious events

Other events: 61 other events

Deaths: 0 deaths

Arm II

Serious events: 6 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

SWOG melanoma statistician

SWOG Statistical Office

Phone: 206-667-4408

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I n=63 participants at risk Sorafenib and Temsirolimu	Arm II n=39 participants at risk Sorafenib and Tipifarnib
Blood and lymphatic system disorders Hemoglobin	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Cardiac disorders Left ventricular systolic dysfunction	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Gastrointestinal disorders Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Gastrointestinal disorders Nausea	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Gastrointestinal disorders Pain - Abdomen NOS	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Gastrointestinal disorders Pancreatitis	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Gastrointestinal disorders Vomiting	3.2% 2/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
General disorders Fatigue (asthenia, lethargy, malaise)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Nose	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Investigations Amylase	0.00% 0/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Investigations Lipase	0.00% 0/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Metabolism and nutrition disorders Dehydration	3.2% 2/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	3.2% 2/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	3.2% 2/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	3.2% 2/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Musculoskeletal and connective tissue disorders Pain - Back	0.00% 0/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Musculoskeletal and connective tissue disorders Pain - Joint	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Nervous system disorders Neurology-Other (Specify)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Nervous system disorders Neuropathy: motor	0.00% 0/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Nervous system disorders Pain - Head/headache	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Psychiatric disorders Confusion	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Renal and urinary disorders Renal failure	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	3.2% 2/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-Other (Specify)	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Skin and subcutaneous tissue disorders Pruritus/itching	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Skin and subcutaneous tissue disorders Rash/desquamation	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Vascular disorders Flushing	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	0.00% 0/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Vascular disorders Hypertension	1.6% 1/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment
Vascular disorders Thrombosis/thrombus/embolism	0.00% 0/63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment	2.6% 1/39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported Regular investigator assessments are reported after each cycle of protocol treatment