Gemcitabine +/- Imatinib Mesylate, Patients w/Previously Treated Metastatic Breast Cancer

• Sponsor: Rutgers, The State University of New Jersey (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00323063
• Collaborator: National Cancer Institute (NCI) (NIH), Novartis Pharmaceuticals (Industry), Rutgers Cancer Institute of New Jersey (Other)
• Enrollment: 49
• Locations: 9
• Arms: 2
• Actual Duration (Months): 121.7
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying gemcitabine and imatinib mesylate to see how well they work compared to gemcitabine alone in treating patients with previously treated locally advanced or metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: gemcitabine hydrochloride; Drug: imatinib mesylate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Compare time to progression in patients with previously treated locally advanced or metastatic breast cancer treated with gemcitabine hydrochloride with vs without imatinib mesylate.

Secondary

• Compare the efficacy of these regimens in these patients.

• Compare the overall survival of patients treated with these regimens.

• Compare the safety and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine hydrochloride IV on days 3 and 10.

• Arm II: Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12.

In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trial of Gemcitabine and Imatinib Mesylate Versus Gemcitabine Alone in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer
• Actual Study Start Date: May 1, 2006
• Actual Primary Completion Date: Apr 15, 2011
• Actual Study Completion Date: Jun 20, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (Gemcitabine Hydrochloride) Patients receive gemcitabine hydrochloride IV on days 3 and 10.	Drug: gemcitabine hydrochloride; Given IV
Experimental: Arm II (Gemcitabine Hydrochloride + Imatinib) Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12.	Drug: gemcitabine hydrochloride; Given IV; Drug: imatinib mesylate; Given orally

Outcome Measures

Primary Outcome Measures

1. Time to Progression [5 years]

   Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided).

Secondary Outcome Measures

1. Response Rate (Complete and Partial Response) [5 years]

   Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response(OR) defined as OR=CR + PR

2. Overall Survival [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Locally advanced or metastatic disease

• Disease progression after at least 1 prior chemotherapy regimen for metastatic disease

• No more than 2 prior chemotherapy regimens for metastatic disease (prior neoadjuvant or adjuvant treatment will not be included in determining the number of prior chemotherapy regimens)

• Measurable disease

• No known symptomatic or untreated brain metastases or carcinomatous meningitis

• Previously treated and clinically stable brain metastases allowed provided patient has been off steroids for > 7 days

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Male or female

• Menopausal status not specified

• ECOG performance status 0-2

• Life expectancy ≥ 3 months

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST or ALT ≤ 2.5 times ULN

• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study therapy

• Able to swallow oral medication

• No coexisting medical condition that would preclude study compliance

• No uncontrolled illness, including any of the following:

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia requiring therapy

• Myocardial infarction within the past 6 months

• Active infection

• No New York Heart Association class III-IV cardiac disease

• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to gemcitabine hydrochloride and/or imatinib mesylate

• No other primary malignancies within the past 5 years except for carcinoma in situ of the cervix or nonmelanoma skin cancer

• No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis)

• No known HIV infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy

• More than 2 weeks since prior surgery

• At least 2 weeks since prior hormonal therapy

• At least 2 weeks since prior trastuzumab (Herceptin®)

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

• At least 3 weeks since prior anti-vascular endothelial growth factor therapy

• More than 28 days since prior investigational agents

• At least 3 weeks since prior radiotherapy

• Must have evidence of ≥ 1 measurable target lesion outside the irradiated fields OR radiologically confirmed disease progression within the irradiated fields after completion of radiotherapy

• No prior imatinib mesylate for metastatic disease

• No prior gemcitabine hydrochloride for metastatic disease

• More than 6 months since prior adjuvant gemcitabine hydrochloride

• No other concurrent investigational or commercial agents

• No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin® or Coumadine®)

• Concurrent heparin or low-molecular weight heparin (e.g., Lovenox®) for therapeutic anticoagulation allowed

• Concurrent prophylactic warfarin therapy (e.g., mini-dose Coumadin® ≤ 1 mg daily) to maintain catheter patency allowed

• No concurrent routine chronic systemic corticosteroids

• No concurrent medications that would preclude study compliance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
2	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
3	Cooper Hospital/University Medical Center	Camden	New Jersey	United States	08103
4	Rutgers Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey	United States	08690
5	Mountainside Hospital	Montclair	New Jersey	United States	07042
6	Jersey Shore Cancer Center at Jersey Shore University Medical Center	Neptune	New Jersey	United States	07754
7	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
8	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08903
9	NJ Medical School	Newark	New Jersey	United States	07103

Sponsors and Collaborators

• Rutgers, The State University of New Jersey
• National Cancer Institute (NCI)
• Novartis Pharmaceuticals
• Rutgers Cancer Institute of New Jersey

Investigators

• Principal Investigator: Deborah R. Toppmeyer, MD, Rutgers Cancer Institute of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Breast cancer - triple negative/cytotoxics/local therapy

Publications

None provided.

• Responsible Party: Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT00323063
• Other Study ID Numbers: 0220060081; P30CA072720; CDR0000539445; 0220060081; NJ1105; NCI-2012-00520; 040504
• First Posted: May 9, 2006
• Last Update Posted: Sep 21, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Rutgers, The State University of New Jersey: recurrent breast cancer; stage IV breast cancer; male breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Imatinib Mesylate

Study Results

Participant Flow

Recruitment Details	This study was opened to accural on 5/1/2006 and was closed to accrual on 4/15/2011 due to slow accrual. Subjects were recruited through the Cancer Institute of New Jersey Oncology Group. We are reporting results on 49 eligible patients. One was not eligible for participation.

Arm/Group Title	Gemcitabine Hydrochloride	Gemcitabine Hydrochloride + Imatinib
Arm/Group Description	Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10. gemcitabine hydrochloride: Given IV	Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10 and oral imatinib mesylate 400 mg orally once daily on days 1-5 and 8-12. gemcitabine hydrochloride: Given IV imatinib mesylate: Given orally
Period Title: Overall Study
STARTED	26	23
COMPLETED	24	23
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Arm I	Arm II	Total
Arm/Group Description	Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10. gemcitabine hydrochloride: Given IV	Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10 and oral imatinib mesylate 400 mg orally once daily on days 1-5 and 8-12. gemcitabine hydrochloride: Given IV imatinib mesylate: Given orally	Total of all reporting groups
Overall Participants	26	23	49
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 57.7%	13 56.5%	28 57.1%
>=65 years	11 42.3%	10 43.5%	21 42.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.7	62.4	61.5
Sex: Female, Male (Count of Participants)
Female	26 100%	23 100%	49 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.7%	1 4.3%	3 6.1%
Not Hispanic or Latino	24 92.3%	22 95.7%	46 93.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 7.7%	1 4.3%	3 6.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 26.9%	6 26.1%	13 26.5%
White	17 65.4%	16 69.6%	33 67.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	23 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	Time to Progression
Description	Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Gemcitabine Hydrochloride)	Arm II (Gemcitabine Hydrochloride + Imatinib)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV on days 3 and 10. gemcitabine hydrochloride: Given IV	Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. gemcitabine hydrochloride: Given IV imatinib mesylate: Given orally
Measure Participants	26	23
Median (95% Confidence Interval) [months]	2	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Gemcitabine Hydrochloride), Arm II (Gemcitabine Hydrochloride + Imatinib)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Response Rate (Complete and Partial Response)
Description	Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response(OR) defined as OR=CR + PR
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Gemcitabine Hydrochloride)	Arm II (Gemcitabine Hydrochloride + Imatinib)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV on days 3 and 10. gemcitabine hydrochloride: Given IV	Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. gemcitabine hydrochloride: Given IV imatinib mesylate: Given orally
Measure Participants	26	23
Number (95% Confidence Interval) [percentage of participants]	9.1 35%	9.1 39.6%

3. Secondary Outcome

Title	Overall Survival
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

This study was prematurely closed so overall survival was not analyzed.

Arm/Group Title	Arm I (Gemcitabine Hydrochloride)	Arm II (Gemcitabine Hydrochloride + Imatinib)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV on days 3 and 10. gemcitabine hydrochloride: Given IV	Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. gemcitabine hydrochloride: Given IV imatinib mesylate: Given orally
Measure Participants	0	0

Adverse Events

Arm/Group Title	Arm I (Gemcitabine Hydrochloride)		Arm II (Gemcitabine Hydrochloride + Imatinib)
Arm/Group Description	Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10. gemcitabine hydrochloride: Given IV		Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10 and oral imatinib mesylate 400 mg orally once daily on days 1-5 and 8-12. gemcitabine hydrochloride: Given IV imatinib mesylate: Given orally
All Cause Mortality
	Arm I (Gemcitabine Hydrochloride)		Arm II (Gemcitabine Hydrochloride + Imatinib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		2/23 (8.7%)
Serious Adverse Events
	Arm I (Gemcitabine Hydrochloride)		Arm II (Gemcitabine Hydrochloride + Imatinib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/26 (19.2%)		6/23 (26.1%)
Gastrointestinal disorders
Vomiting	2/26 (7.7%)	2	1/23 (4.3%)	1
General disorders
Fever	2/26 (7.7%)	2	0/23 (0%)	0
Infections and infestations
Lung Infection	0/26 (0%)	0	1/23 (4.3%)	1
Investigations
Neutrophils decreased	0/26 (0%)	0	1/23 (4.3%)	1
Anemia	0/26 (0%)	0	1/23 (4.3%)	1
Metabolism and nutrition disorders
Dehydration	2/26 (7.7%)	2	2/23 (8.7%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/26 (0%)	0	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Gemcitabine Hydrochloride)		Arm II (Gemcitabine Hydrochloride + Imatinib)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		23/23 (100%)
Blood and lymphatic system disorders
Anemia	13/26 (50%)	31	8/23 (34.8%)	40
Eye disorders
Dry eye	0/26 (0%)	0	1/23 (4.3%)	1
Gastrointestinal disorders
Vomiting	5/26 (19.2%)	6	3/23 (13%)	11
Nausea	9/26 (34.6%)	12	5/23 (21.7%)	17
Diarrhea	0/26 (0%)	0	1/23 (4.3%)	5
Dyspepsia	0/26 (0%)	0	1/23 (4.3%)	3
Mucositis oral	1/26 (3.8%)	1	0/23 (0%)	0
General disorders
Fatigue	10/26 (38.5%)	16	4/23 (17.4%)	14
Fever	5/26 (19.2%)	5	1/23 (4.3%)	1
Infections and infestations
Lung Infection	0/26 (0%)	0	1/23 (4.3%)	1
Investigations
alkaline phosphatase increased	1/26 (3.8%)	2	0/23 (0%)	0
Alanine aminotransferase	4/26 (15.4%)	5	1/23 (4.3%)	1
White blood cell decreased	14/26 (53.8%)	30	7/23 (30.4%)	39
Blood bilirubin increased	0/26 (0%)	0	1/23 (4.3%)	2
Neutrophil count decreased	20/26 (76.9%)	45	10/23 (43.5%)	57
Platelet count decreased	7/26 (26.9%)	16	5/23 (21.7%)	20
Aspartate aminoransferase elevated	0/26 (0%)	0	1/23 (4.3%)	1
Creatinine increased	0/26 (0%)	0	1/23 (4.3%)	1
Metabolism and nutrition disorders
Anorexia	2/26 (7.7%)	2	1/23 (4.3%)	2
Dehydration	1/26 (3.8%)	1	1/23 (4.3%)	1
Musculoskeletal and connective tissue disorders
Bone Pain	1/26 (3.8%)	1	0/23 (0%)	0
Myalgia	1/26 (3.8%)	1	0/23 (0%)	0
Nervous system disorders
Syncope	0/26 (0%)	0	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/26 (0%)	0	1/23 (4.3%)	1
Skin and subcutaneous tissue disorders
Alopecia	8/26 (30.8%)	8	8/23 (34.8%)	8
Nail discoloration	2/26 (7.7%)	3	0/23 (0%)	0
Rash maculo-papular	2/26 (7.7%)	2	1/23 (4.3%)	3
Pruritus	1/26 (3.8%)	1	1/23 (4.3%)	1
Vascular disorders
Hot flashes	1/26 (3.8%)	1	1/23 (4.3%)	1

Limitations/Caveats

This study was underpowered to draw any conclusion regarding a difference in TTP between the two groups at the time is was prematurely closed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.