Trial Outcomes & Findings for Sorafenib and Vinorelbine in Treating Women With Stage IV Breast Cancer (NCT NCT00828074)

Last Updated: 2017-02-27

Results Overview

Dose Limiting Toxicity (DLT) defined as any treatment-related grade 3 or greater non-hematologic toxicity (excluding alopecia, controllable nausea and vomiting, and serum triglycerides \< 1,500 mg/dL which recover within 1 week), grade 4 or greater thrombocytopenia, grade 4 or greater febrile neutropenia requiring hospitalization, or treatment delay of \> 2 weeks as a result of unresolved toxicity during the first cycle of therapy.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

46 participants

Primary outcome timeframe

4 weeks from start of treatment, up to 2 years

Results posted on

2017-02-27

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I - Vinorelbine at 20mg/m^2 Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase II - Vinorelbine 20mg/m^2 Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Overall Study STARTED	6	5	35
Overall Study COMPLETED	6	5	35
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sorafenib and Vinorelbine in Treating Women With Stage IV Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 - Vinorelbine at 20mg/m^2 n=41 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Dose Level 2 - Vinorelbine at 25mg/m^2 n=5 Participants Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Total n=46 Participants Total of all reporting groups
Age, Continuous	54 years n=99 Participants	59 years n=107 Participants	55 years n=206 Participants
Gender Female	41 Participants n=99 Participants	5 Participants n=107 Participants	46 Participants n=206 Participants
Gender Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	41 participants n=99 Participants	5 participants n=107 Participants	46 participants n=206 Participants

PRIMARY outcome

Timeframe: 4 weeks from start of treatment, up to 2 years

Population: All patients receiving treatment were evaluated for DLT.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=6 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 n=5 Participants Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Number of Participants With at Least One Dose Limiting Toxicity in Phase I	0 participants with DLTs	3 participants with DLTs

PRIMARY outcome

Timeframe: 4 weeks from start of treatment, up to 2 years

Population: All patients observed for 28 days while receiving a full course of therapy or who experienced a DLT. Patients withdrawing before completion of the first course, for reasons other than DLT, were replaced.

The maximum tolerated dose (MTD) of Vinorelbine is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=11 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Recommended Phase II Dose	20 mg/m^2	—

SECONDARY outcome

Timeframe: 4 months following the last course of treatment

Population: All patients treated at the phase II vinorelbine dose (6 in the phase I portion, 35 in the phase II portion).

Estimated using the product-limit method of Kaplan and Meier.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=41 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Progression-free Survival Rate at 4 Months	44 percentage of participants	—

SECONDARY outcome

Timeframe: Until disease progression, up to 5 years.

Population: All patients treated at the phase II vinorelbine dose (6 in the phase I portion, 35 in the phase II portion).

Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=41 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Progression-free Survival	4.1 Months Interval 2.6 to 5.3	—

SECONDARY outcome

Timeframe: After 2 cycles of treatment, up to 2 years.

Population: All patients treated at the phase II vinorelbine dose (6 in the phase I portion, 35 in the phase II portion). Patients who complete 2 cycles of treatment or who terminate treatment for reasons of toxicity, or who progress prior to the completion of 2 cycles of therapy on the Phase II portion of the study.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate defined as percentage of patients achieving a Best Response of either CR or PR.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=41 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Objective Response Rate	10 percentage of participants	—

SECONDARY outcome

Timeframe: Until death from any cause, up to 5 years.

Population: All patients treated at the phase II vinorelbine dose (6 in the phase I portion, 35 in the phase II portion).

Estimated using the product-limit method of Kaplan and Meier.

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=41 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Overall Survival	15.4 Months Interval 11.6 to 28.9	—

SECONDARY outcome

Timeframe: 28 days following the last course of treatment

Number of Participants with Treatment-Related Grade 3 \& 4 Toxicities for Sorafenib and Vinorelbine Combination

Outcome measures

Outcome measures
Measure	Phase I: Dose Level 1 - Vinorelbine at 20mg/m^2 n=46 Participants Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Phase I: Dose Level 2 - Vinorelbine at 25mg/m^2 Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Toxicity Profile Anemia	2 participants	—
Toxicity Profile Leukopenia	16 participants	—
Toxicity Profile Neutropenia	16 participants	—
Toxicity Profile Thrombocytopenia	1 participants	—
Toxicity Profile Alkalosis	1 participants	—
Toxicity Profile Cellulitis	1 participants	—
Toxicity Profile Cough	1 participants	—
Toxicity Profile Diarrhea	3 participants	—
Toxicity Profile Fatigue	5 participants	—
Toxicity Profile Genital abscess	1 participants	—
Toxicity Profile Hand-foot toxicity	7 participants	—
Toxicity Profile Hiccups	1 participants	—
Toxicity Profile High glucose level	1 participants	—
Toxicity Profile Hypertension	3 participants	—
Toxicity Profile Hypokalemia	1 participants	—
Toxicity Profile Hyponatremia	2 participants	—
Toxicity Profile Infection (NOS)	1 participants	—
Toxicity Profile Low phosphate	3 participants	—
Toxicity Profile Pulmonary embolus	1 participants	—
Toxicity Profile Myalgia	1 participants	—
Toxicity Profile Pain (NOS)	3 participants	—
Toxicity Profile Phlebitis	1 participants	—
Toxicity Profile Sensory neuropathy	1 participants	—
Toxicity Profile Somnolence	1 participants	—
Toxicity Profile Transaminases/alkaline	1 participants	—
Toxicity Profile Urinary tract infection	1 participants	—

Adverse Events

Dose Level 1 - Vinorelbine at 20mg/m^2

Serious events: 15 serious events

Other events: 41 other events

Deaths: 0 deaths

Dose Level 2 - Vinorelbine at 25mg/m^2

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 626-359-8111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose Level 1 - Vinorelbine at 20mg/m^2 n=41 participants at risk Vinorelbine at 20mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days	Dose Level 2 - Vinorelbine at 25mg/m^2 n=5 participants at risk Vinorelbine at 25mg/m\^2 weekly intravenous (I.V.) on days 1, 8, 15 and sorafenib 200 mg given orally (p.o.) twice daily for 28 days
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/41 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Stomach pain	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	4.9% 2/41 • Number of events 2 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Immune system disorders Cytokine release syndrome	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Infection	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Skin infection	4.9% 2/41 • Number of events 2 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Coagulopathy	0.00% 0/41 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations INR increased	0.00% 0/41 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lipase increased	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Neutrophil count decreased	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum glucose decreased	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Bone pain	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Chest wall pain	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Depressed level of consciousness	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Thrombosis	2.4% 1/41 • Number of events 1 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse Events collected over a period of 22 months. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.