BrUOG-PA-209: Lapatinib and Gemcitabine for Metastatic Pancreaticobiliary Cancer

• Sponsor: Brown University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00447122
• Collaborator: Rhode Island Hospital (Other), The Miriam Hospital (Other), Memorial Hospital of Rhode Island (Other)
• Enrollment: 25
• Location: 1
• Arms: 4
• Duration (Months): 17.1
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Phase I study of lapatinib and gemcitabine for patients with metastatic pancreaticobiliary cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Cancer	Drug: Gemcitabine 1000mg/m2 30 minutes; Drug: Lapatinib 1000mg/d; Drug: Lapatinib 1500mg/d; Drug: Gemcitabine 1000mg/m2 100minutes; Drug: Oxaliplatin 100mg/m2	Phase 1

Detailed Description

To evaluate the safety/tolerability and potential antitumor activity of lapatinib, at dose ranges of 1000 to 1500 mg/d, in combination with gemcitabine and gemcitabine/oxaliplatin (GEMOX) in patients with advanced pancreaticobiliary cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BrUOG-PA-209: Lapatinib and Gemcitabine for Metastatic Pancreaticobiliary Cancer: A Phase I Study #108181
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment 1 Gemcitabine 1000mg/m2 with lapatinib 1000mg/d weekly x 3 weeks	Drug: Gemcitabine 1000mg/m2 30 minutes; 1000mg/m2 30 minutes; Other Names: Gemzar ; Drug: Lapatinib 1000mg/d; 1000mg/d; Other Names: Tykerb Tyverb
Experimental: treatment 2 Gemcitabine 1000mg/m2 with lapatinib 1500mg/d weekly X 3 weeks	Drug: Gemcitabine 1000mg/m2 30 minutes; 1000mg/m2 30 minutes; Other Names: Gemzar ; Drug: Lapatinib 1500mg/d; 1500mg/d; Other Names: Tykerb Tyverb
Experimental: treatment 3 gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 on days 1 and 14 of a 28-day cycle with lapatinib 1000 mg/d	Drug: Lapatinib 1000mg/d; 1000mg/d; Other Names: Tykerb Tyverb ; Drug: Gemcitabine 1000mg/m2 100minutes; 1000mg/m2 100minutes; Other Names: Gemzar ; Drug: Oxaliplatin 100mg/m2; 100mg/m2; Other Names: Eloxatin
Experimental: treatment 4 gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 on days 1 and 14 of a 28-day cycle with lapatinib 1500 mg/d	Drug: Lapatinib 1500mg/d; 1500mg/d; Other Names: Tykerb Tyverb ; Drug: Gemcitabine 1000mg/m2 100minutes; 1000mg/m2 100minutes; Other Names: Gemzar ; Drug: Oxaliplatin 100mg/m2; 100mg/m2; Other Names: Eloxatin

Outcome Measures

Primary Outcome Measures

1. Overall Survival for Patients With Metastatic Pancreatic Cancer. [Date of study entry until the date of death, up to 12 months.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients are required to have histologically or pathologically confirmed, metastatic adenocarcinoma of the pancreas

• No prior chemotherapy for pancreatic cancer.

• ECOG performance status 0-1

• Must retain ability to swallow oral medications

• Age > 18. Because no dosing or adverse event data are currently available on the use of lapatinib in patients < 18 years of age, children are excluded from this study.

• Women of child bearing potential must be non pregnant and non lactating.The effects of lapatinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female is eligible to enter and participate in the study if she is of:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:

• Has had a hysterectomy,

• Has had a bilateral oophorectomy (ovariectomy),

• Has had a bilateral tubal ligation, or

• Is post-menopausal(demonstration of total cessation of menses for ³1 year).

• Childbearing potential, has a negative serum pregnancy test within 2 weeks prior to treatment to rule out pregnancy.

• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment.

• Intrauterine Device (IUD),

• Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.

• Complete abstinence from sexual intercourse for two weeks before exposure to investigational products, throughout the clinical trial, and for at least one week after the last dose of investigational product.

• Double barrier contraception (condom with spermicidal jelly, foam, suppository, or film; diaphragm with spermicide; or male condom and diaphragm).

• Vasectomy

• Adequate hematologic function: ANC ≥ 1500/ul, platelets ≥ 100,000/ul. Adequate hepatic function with total bilirubin ≤ 2.0 mg/dL and ALT or AST ≤ 2x ULN. (Patients with liver metastases may have AST/ALT less than or equal to 5x upper limit of normal).

• Adequate renal function: creatinine ≤ 2.0 mg/dL

• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution.

• Life expectancy of at least 12 weeks

• Signed informed consent

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Prior treatment with lapatinib or any EGFR targeting therapies.

• Prior treatment with systemic chemotherapy for pancreatic cancer.

• Clinical evidence of brain metastases or leptomeningeal disease

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Active cardiac disease, defined as:

• History of uncontrolled angina

• Myocardial infarction < 6 months from study entry

• Uncontrolled or symptomatic congestive heart failure

• Ejection fraction below the institutional normal limit

• Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient

• The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug.

• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib

• Participation in any investigational study within 28 days prior to study enrolment

• Any major surgery (insertion of a vascular access device or laparoscopy is not considered a major surgery), within the last 4 weeks.

• Pregnant or lactating females are excluded from this study because lapatinib is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib.

• Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption of lapatinib.

• Any unresolved bowel obstruction.

• The patient has inadequate venous access in the clinical judgment of the investigator or designated clinical staff.

• Patient is taking any medication on the prohibited medications list in

• Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR. If medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with lapatinib is not expected.

• Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lifespan Hospitals	Providence	Rhode Island	United States	02903

Sponsors and Collaborators

• Brown University
• Rhode Island Hospital
• The Miriam Hospital
• Memorial Hospital of Rhode Island

Investigators

• Principal Investigator: Howard Safran, MD, Brown University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Brown University
• ClinicalTrials.gov Identifier: NCT00447122
• Other Study ID Numbers: BrUOG-PA-209
• First Posted: Mar 14, 2007
• Last Update Posted: Mar 8, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Brown University: Pancreatic Cancer
• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Oxaliplatin; Lapatinib

Study Results

Participant Flow

Recruitment Details	25 patients were enrolled

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	lapatinib, 1,000 mg/day, and Gemcitabine, 1000mg/m2	Gem 1000mg/m2, lapatinib 1500mg/d	Gem 1000mg/m2 100 minutes oxaliplatin 100mg/m2 lapatinib 1000mg/d	Gem 1000mg/m2 100 minutes oxaliplatin 100mg/m2 lapatinib 1500mg/d
Period Title: Overall Study
STARTED	3	11	6	5
COMPLETED	3	10	6	5
NOT COMPLETED	0	1	0	0

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4	Total
Arm/Group Description	Gemcitabine, 1000mg/m2 and lapatinib 1000mg/d	Gemcitabine, 1000mg/m2 and lapatinib 1500mg/d	Gemcitabine, 1000mg/m2 over 100minutes lapatinib 1000mg/d oxaliplatin 100mg/m2	Gemcitabine, 1000mg/m2 over 100minutes lapatinib 1500mg/d oxaliplatin 100mg/m2	Total of all reporting groups
Overall Participants	3	11	6	5	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	11 100%	6 100%	5 100%	25 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 66.7%	8 72.7%	4 66.7%	4 80%	18 72%
Male	1 33.3%	3 27.3%	2 33.3%	1 20%	7 28%
Region of Enrollment (participants) [Number]
United States	3 100%	11 100%	6 100%	5 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival for Patients With Metastatic Pancreatic Cancer.
Time Frame	Date of study entry until the date of death, up to 12 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	Gem 1000mg/m2 lapatinib 1000mg/d	Gem 1000mg/m2 lapatinib 1500mg/d	Gem 1000mg/m2 lapatinib 1000mg/d oxaliplatin 100mg/m2	Gem 1000mg/m2 lapatinib 1500mg/d oxaliplatin 100mg/m2
Measure Participants	3	11	6	5
Number [participants]	3 100%	10 90.9%	6 100%	5 100%

Adverse Events

Time Frame	Through study completion, an average of 1 year
Arm/Group Title	Arm 1		Arm 2		Arm 3		Arm 4
Arm/Group Description	Gem 1000mg/m2 lapatinib 1000mg/d		Gem 1000mg/m2 lapatinib 1500mg/d		Gem 1000mg/m2 lapatinib 1000mg/d oxaliplatin 100mg/m2		Gem 1000mg/m2 lapatinib 1500mg/d oxaliplatin 100mg/m2
All Cause Mortality
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/11 (0%)		0/6 (0%)		0/5 (0%)
Serious Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/11 (9.1%)		1/6 (16.7%)		2/5 (40%)
Investigations
pneumocystis sepsis and ARDS	0/3 (0%)	0	1/11 (9.1%)	1	1/6 (16.7%)	1	2/5 (40%)	2
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/11 (9.1%)		1/6 (16.7%)		2/5 (40%)
Gastrointestinal disorders
diarrhea	0/3 (0%)	0	1/11 (9.1%)	11	0/6 (0%)	0	0/5 (0%)	0
nausea	0/3 (0%)	0	0/11 (0%)	0	0/6 (0%)	0	1/5 (20%)	5
General disorders
fatigue	0/3 (0%)	0	0/11 (0%)	0	1/6 (16.7%)	6	0/5 (0%)	0
Metabolism and nutrition disorders
anorexia	0/3 (0%)	0	0/11 (0%)	0	0/6 (0%)	0	1/5 (20%)	5

Limitations/Caveats

Early termination due to slow enrollment and lack of funding.

More Information

Certain Agreements

Principal Investigators are NOT 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.