Trial Outcomes & Findings for Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer (NCT NCT00082810)

NCT ID: NCT00082810

Last Updated: 2018-11-01

Results Overview

Number of participants met the definition of Clinical Benefit Rate.Tumor response was assessed every three cycles by CT using RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Up to 24 weeks

Results posted on

2018-11-01

Participant Flow

A total of 33 patients were enrolled from 3 institutions between March 2004 and August 2006. Two patients were ineligible; one had a performance status of three and elevated liver function tests that exceeded inclusion criteria, whereas the other received prior chemotherapy for metatstatic disease.

Participant milestones

Participant milestones
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Overall Study
STARTED
33
Overall Study
COMPLETED
2
Overall Study
NOT COMPLETED
31

Reasons for withdrawal

Reasons for withdrawal
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Overall Study
Adverse Event
3
Overall Study
Progressive disease
24
Overall Study
Withdrawal by Subject
4

Baseline Characteristics

Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=33 Participants
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Age, Continuous
61.0 years
n=5 Participants
Sex: Female, Male
Female
33 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Whites
14 participants
n=5 Participants
Race/Ethnicity, Customized
Black
3 participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic
14 participants
n=5 Participants
Race/Ethnicity, Customized
Asian
2 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks

Number of participants met the definition of Clinical Benefit Rate.Tumor response was assessed every three cycles by CT using RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=31 Participants
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD)
Partial response
11 participants
Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD)
Stable disease
5 participants
Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD)
Complete response
0 participants

SECONDARY outcome

Timeframe: From randomization until progression of the disease, assessed up to 4 years

TTP was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=31 Participants
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Time to Progression (TTP)
7.2 months
Interval 2.8 to 9.8

SECONDARY outcome

Timeframe: Up to 4 years

DOR was defined for responders as the time from the onset of first response to disease progression and for non-responders as zero

Outcome measures

Outcome measures
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=16 Participants
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Duration of Response
16 months
Interval 5.2 to 19.4

SECONDARY outcome

Timeframe: Up to 4 years

Population: All treated patients who received at least one dose of tipifarnib were included in the safety analysis. A total of 342 cycles of therapy were administered (median 7 cycles/patient range 1-36 cycles)

Number of Participants with serious (grade 3) or life-threatening (grade 4) adverse events

Outcome measures

Outcome measures
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=33 Participants
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Toxicity as Assessed by NCI CTCAE Version 3.0
33 Participants

SECONDARY outcome

Timeframe: From randomization until death or censored at the date of last follow-up, assessed up to 4 years

The 95% confidence intervals will be used.

Outcome measures

Outcome measures
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=31 Participants
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Median Overall Survival
19.4 months
Interval 16.1 to 27.6

Adverse Events

Fulvestrant 250 mg + Tipifarnib 300 mg

Serious events: 20 serious events
Other events: 15 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=33 participants at risk
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Infections and infestations
Infection
3.0%
1/33
Gastrointestinal disorders
Nausea
9.1%
3/33
Gastrointestinal disorders
Vomiting
6.1%
2/33
Gastrointestinal disorders
Diarrhea
3.0%
1/33
Metabolism and nutrition disorders
Anorexia
3.0%
1/33
General disorders
Fatigue
3.0%
1/33
Cardiac disorders
Cardiac Ischemia
3.0%
1/33
Metabolism and nutrition disorders
Hyperglycemia
3.0%
1/33
Metabolism and nutrition disorders
Hypocalcemia
6.1%
2/33
Metabolism and nutrition disorders
Hypokalemia
3.0%
1/33
Psychiatric disorders
Insomnia
3.0%
1/33
Psychiatric disorders
Anxiety
3.0%
1/33
Psychiatric disorders
Agitation
3.0%
1/33
Nervous system disorders
Ataxia
3.0%
1/33
Respiratory, thoracic and mediastinal disorders
Dyspnea
3.0%
1/33
Respiratory, thoracic and mediastinal disorders
Pneumonitis
3.0%
1/33
Renal and urinary disorders
Creatinine
3.0%
1/33
Skin and subcutaneous tissue disorders
Rash
3.0%
1/33
Blood and lymphatic system disorders
Neutropenia
12.1%
4/33
Blood and lymphatic system disorders
Anemia
6.1%
2/33

Other adverse events

Other adverse events
Measure
Fulvestrant 250 mg + Tipifarnib 300 mg
n=33 participants at risk
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Blood and lymphatic system disorders
Anemia
24.2%
8/33
Infections and infestations
Infection
9.1%
3/33
Gastrointestinal disorders
Nausea
36.4%
12/33
Gastrointestinal disorders
Vomiting
12.1%
4/33
Gastrointestinal disorders
Diarrhea
33.3%
11/33
Metabolism and nutrition disorders
Anorexia
18.2%
6/33
General disorders
Fatigue
36.4%
12/33
General disorders
Fever
9.1%
3/33
Metabolism and nutrition disorders
Hyperglycemia
15.2%
5/33
Psychiatric disorders
Insomnia
12.1%
4/33
Nervous system disorders
Neuropathy
21.2%
7/33
Psychiatric disorders
Anxiety
6.1%
2/33
Respiratory, thoracic and mediastinal disorders
Dyspnea
12.1%
4/33
Renal and urinary disorders
Creatinine
6.1%
2/33
Skin and subcutaneous tissue disorders
Rash
6.1%
2/33

Additional Information

NYCC Regulatory Coordinator

Montefiore Medical Center - New York

Phone: 718-379-6862

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60