Gemcitabine/Taxotere/Xeloda (GTX) With Cisplatin in Subjects With Metastatic Pancreatic Cancer

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT01459614
• Collaborator: Swim Across America (Other)
• Enrollment: 44
• Location: 1
• Arm: 1
• Actual Duration (Months): 60
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Primary Objectives

To assess the efficacy of the combination of gemcitabine, taxotere, and xeloda (GTX) with cisplatin in subjects with metastatic pancreatic cancer based on the progression-free survival (PFS) rate at 6 month.

Secondary Objectives

• To assess safety and characterize toxicities of the combination of GTX with cisplatin in subjects with metastatic pancreatic cancer.

• To estimate disease control rate (DCR), PFS, and overall survival (OS).

• To estimate a PFS rate of an expansion cohort testing an alternative schedule.

Study Design

This study is a single arm phase II study to assess the efficacy of GTX with cisplatin in subjects with metastatic pancreatic cancer. Approximately 38 evaluable subjects will be enrolled, 28 in the initial cohort and 10 in the expansion cohort

The study will have a safety run-in phase consisting of 6 subjects. To ensure that the combination is safe, the first six subjects will be treated at DL1 and observed for limiting toxicity for the first 2 cycles before continuation with further accrual. After the safety run-in, the study will be continuously monitored for adverse events.

The primary endpoint will be the PFS rate at 6 month, which is defined as the proportion of subjects alive, free of disease progression at 6 months. The treatment regimen would be considered of insufficient activity for further study in this population if PFS rate at 6 months is 50% or less, and the minimum required level of efficacy that would warrant further study with the proposed regimen is a 75% PFS rate at 6 months. The study design includes interim monitoring for futility using a predictive probability approach. We will stop the study early if given the information at the interim analysis, it is unlikely that the PFS rate at 6 months will be greater than 50% if the study continues to the end.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: Gemcitabine; Drug: Taxotere; Drug: Xeloda; Drug: Cisplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin in Subjects With Metastatic Pancreatic Cancer
• Actual Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GTX-C Each cycle is 21 days (2 weeks Tx + 1 week off). Xeloda given days 1-14, Gemcitabine, Taxotere, and Cisplatin given days 4 and 11. For expansion cohort, each cycle is 28 days (2 weeks of Tx + 2 weeks off)	Drug: Gemcitabine; IV on Days 4 and 11; Drug: Taxotere; IV on Days 4 and 11; Other Names: Docetaxel ; Drug: Xeloda; orally, twice a day Days 1-14; Other Names: Capecitabine ; Drug: Cisplatin; IV Days 4 and 11; Other Names: Platinol CDDP

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Without Disease Progression (Progression-Free Survival) at 6 Months [6 months]

   PFS is defined as the percentage of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

Secondary Outcome Measures

1. Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity [Up to 23 months]

   When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. AEs collected from time of first dose of study drug through 28 days after the last dose of study drug. The median duration of treatment was up to 23 months.

2. Disease Control Rate (DCR) [Up to 22 months]

   DCR is defined as the percentage of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.

3. Progression-free Survival (PFS) [Up to 21 months]

   PFS is defined as the the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause . Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

4. Overall Survival (OS) [Up to 28 months]

   OS (in months) will be measured from date of first dose until death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. Subjects with islet cell neoplasms are excluded. Subjects with mixed histology will be excluded.

• Subject has one or more tumors measurable by CT scan using RECIST 1.1 criteria. MRI is acceptable if a CT scan is contraindicated.

• Patient must be chemotherapy naïve or must have completed chemotherapy greater than 5 years prior to enrollment.

• Male or non-pregnant and non-lactating female of age >18 years

• ECOG performance status <1. ECOG 0 indicates that the patient is fully active and able to carry on all pre-disease activities without restriction; and, ECOG 1 indicates that the patient is restricted in physically strenuous activity but is ambulatory and able to carry out work of a light or sedentary nature

• Life expectancy of greater than 12 weeks.

• Subjects must have adequate organ and marrow function as defined below:

WBC ≥ 3,500/mcL Absolute Neutrophil Count ≥1,500/mcL Platelets ≥100 x 10^9/L Hemoglobin ≥ 9 g/d Total Bilirubin within normal institutional limits Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X ULN for subjects with documented liver metastases) AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5 X ULN for subjects with documented liver metastases) Creatinine within normal institutional limits OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

• Willingness to undergo a tumor biopsy (implemented after the first 6 patients).

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Subjects who have had any prior chemotherapy within 5 years of enrollment

• Subjects who have had radiotherapy for pancreatic cancer.

• Age ≥ 76 years

• Subjects who are receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study.

• Subject has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to Day 1 of treatment in this study.

• Subject has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids).

• History of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, taxotere, xeloda, or cisplatin.

• 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.

• Subject has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the subject to receive an experimental research drug.

• Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

• Subject has a known history of infection with HIV, hepatitis B, or hepatitis C.

• Subject is pregnant or breast feeding.

• Subject is unwilling or unable to comply with study procedures.

• Subject with an unhealed surgical wound or other clinically significant wound.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Swim Across America

Investigators

• Principal Investigator: Dung Le, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01459614
• Other Study ID Numbers: J11125; NA_00066595; Swim Across America Laboratory
• First Posted: Oct 25, 2011
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Docetaxel; Capecitabine

Study Results

Participant Flow

Pre-assignment Detail	44 patients were consented and screened. Of these, 5 were screen failures and 39 were eligible and assigned to receive treatment.

Arm/Group Title	Primary Cohort (21 Day Cycle)	Expansion Cohort (28 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.	Each cycle is 28 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
Period Title: Overall Study
STARTED	29	10
COMPLETED	28	10
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Primary Cohort (21 Day Cycle)	Expansion Cohort (28 Day Cycle)	Total
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.	Each cycle is 28 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.	Total of all reporting groups
Overall Participants	29	10	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	67	62
Sex: Female, Male (Count of Participants)
Female	13 44.8%	2 20%	15 38.5%
Male	16 55.2%	8 80%	24 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.4%	2 20%	3 7.7%
Not Hispanic or Latino	28 96.6%	8 80%	36 92.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	29 100%	10 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Without Disease Progression (Progression-Free Survival) at 6 Months
Description	PFS is defined as the percentage of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

One patient was consented and enrolled, but was not considered evaluable per protocol, as he came off study prior to completing a cycle of treatment for reasons other than disease progression or death.

Arm/Group Title	Primary Cohort (21 Day Cycle)	Expansion Cohort (28 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.	Each cycle is 28 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
Measure Participants	28	10
Number (95% Confidence Interval) [percentage of participants]	78.6 271%	30 300%

2. Secondary Outcome

Title	Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
Description	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. AEs collected from time of first dose of study drug through 28 days after the last dose of study drug. The median duration of treatment was up to 23 months.
Time Frame	Up to 23 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Primary Cohort (21 Day Cycle)	Expansion Cohort (28 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.	Each cycle is 28 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
Measure Participants	29	10
Count of Participants [Participants]	26 89.7%	5 50%

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR is defined as the percentage of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

Outcome was assessed for the Primary Cohort only per protocol. One patient was consented and enrolled, but was not considered evaluable per protocol, as he came off study prior to completing a cycle of treatment for reasons other than disease progression or death.

Arm/Group Title	Primary Cohort (21 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
Measure Participants	28
Number (95% Confidence Interval) [Percentage of Participants]	89 306.9%

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined as the the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause . Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description

One patient was consented and enrolled, but was not considered evaluable per protocol, as he came off study prior to completing a cycle of treatment for reasons other than disease progression or death.

Arm/Group Title	Primary Cohort (21 Day Cycle)	Expansion Cohort (28 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.	Each cycle is 28 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
Measure Participants	28	10
Median (95% Confidence Interval) [Months]	8.4	4.1

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS (in months) will be measured from date of first dose until death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.
Time Frame	Up to 28 months

Outcome Measure Data

Analysis Population Description

Outcome was assessed for the Primary Cohort only per protocol. One patient was consented and enrolled, but was not considered evaluable per protocol, as he came off study prior to completing a cycle of treatment for reasons other than disease progression or death.

Arm/Group Title	Primary Cohort (21 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
Measure Participants	28
Median (95% Confidence Interval) [Months]	13.42

Adverse Events

Time Frame	AEs collected from time of first dose of study drug through 28 days after the last dose of study drug. The median duration of treatment was up to 23 months.
Adverse Event Reporting Description	AEs collected during protocol-specified visits, labs, and quality of life surveys.
Arm/Group Title	Primary Cohort (21 Day Cycle)		Expansion Cohort (28 Day Cycle)
Arm/Group Description	Each cycle is 21 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.		Each cycle is 28 days. Xeloda (PO BID) given days 1-14, Gemcitabine (IV), Taxotere (IV), and Cisplatin (IV) given days 4 and 11.
All Cause Mortality
	Primary Cohort (21 Day Cycle)		Expansion Cohort (28 Day Cycle)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/29 (82.8%)		7/10 (70%)
Serious Adverse Events
	Primary Cohort (21 Day Cycle)		Expansion Cohort (28 Day Cycle)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)		1/10 (10%)
Blood and lymphatic system disorders
febrile neutropenia	3/29 (10.3%)		0/10 (0%)
Gastrointestinal disorders
mucositis	1/29 (3.4%)		0/10 (0%)
nausea	1/29 (3.4%)		0/10 (0%)
vomiting	1/29 (3.4%)		0/10 (0%)
Investigations
neutrophil count decreased	1/29 (3.4%)		0/10 (0%)
Nervous system disorders
intracranial hemorrhage	0/29 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Primary Cohort (21 Day Cycle)		Expansion Cohort (28 Day Cycle)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anemia	19/29 (65.5%)		3/10 (30%)
leukopenia	2/29 (6.9%)		0/10 (0%)
Lymphopenia	10/29 (34.5%)		3/10 (30%)
Neutropenia	21/29 (72.4%)		3/10 (30%)
Thrombocytopenia	9/29 (31%)		4/10 (40%)
Ear and labyrinth disorders
Ear pain	2/29 (6.9%)		0/10 (0%)
Hearing impairment	0/29 (0%)		1/10 (10%)
Tinnitus	0/29 (0%)		1/10 (10%)
Eye disorders
Photophobia	0/29 (0%)		1/10 (10%)
Blurred vision	3/29 (10.3%)		0/10 (0%)
Vision Changes	3/29 (10.3%)		0/10 (0%)
Watering eyes	4/29 (13.8%)		0/10 (0%)
Gastrointestinal disorders
Abdominal Pain	0/29 (0%)		1/10 (10%)
Anorexia	4/29 (13.8%)		2/10 (20%)
Bloating	0/29 (0%)		1/10 (10%)
Colitis	0/29 (0%)		1/10 (10%)
Constipation	3/29 (10.3%)		0/10 (0%)
Diarrhea	15/29 (51.7%)		7/10 (70%)
Dry Mouth	2/29 (6.9%)		0/10 (0%)
Flatulence	3/29 (10.3%)		1/10 (10%)
Hiccups	0/29 (0%)		1/10 (10%)
Indigestion or GERD	3/29 (10.3%)		2/10 (20%)
Mouth sores	4/29 (13.8%)		0/10 (0%)
Nausea	16/29 (55.2%)		3/10 (30%)
Vomiting	10/29 (34.5%)		6/10 (60%)
Weight loss	3/29 (10.3%)		0/10 (0%)
General disorders
Chest pain	0/29 (0%)		1/10 (10%)
Edema	2/29 (6.9%)		3/10 (30%)
Fatigue	12/29 (41.4%)		2/10 (20%)
Fever	4/29 (13.8%)		1/10 (10%)
Infusion reaction	0/29 (0%)		1/10 (10%)
Night sweats	0/29 (0%)		1/10 (10%)
Infections and infestations
Thrush	3/29 (10.3%)		4/10 (40%)
Investigations
ALT, increased	3/29 (10.3%)		0/10 (0%)
AST, increased	1/29 (3.4%)		1/10 (10%)
Bilirubin, increased	0/29 (0%)		1/10 (10%)
Creatinine, increased	2/29 (6.9%)		2/10 (20%)
Metabolism and nutrition disorders
Dehydration	2/29 (6.9%)		0/10 (0%)
Hypokalemia	4/29 (13.8%)		0/10 (0%)
Hypomagnesemia	16/29 (55.2%)		4/10 (40%)
Nervous system disorders
Dizziness	5/29 (17.2%)		0/10 (0%)
Dysgeusia	17/29 (58.6%)		3/10 (30%)
Neuropathy	12/29 (41.4%)		3/10 (30%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	4/29 (13.8%)		2/10 (20%)
Rhinitis	3/29 (10.3%)		0/10 (0%)
Smell Sensitivity	2/29 (6.9%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Alopecia	25/29 (86.2%)		8/10 (80%)
Blisters	2/29 (6.9%)		0/10 (0%)
Dry skin	4/29 (13.8%)		2/10 (20%)
Nail Changes	10/29 (34.5%)		3/10 (30%)
Rash	0/29 (0%)		1/10 (10%)
Vascular disorders
Hypotension	0/29 (0%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

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.