Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00331682
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Drugs used in chemotherapy, such as docetaxel and flavopiridol, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Flavopiridol may also help docetaxel work better by making tumor cells more sensitive to the drug. This phase II trial is studying how well giving docetaxel followed by flavopiridol works in treating patients with refractory metastatic pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: alvocidib; Drug: docetaxel	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the response rate in patients with refractory, metastatic pancreatic cancer treated with weekly, sequential docetaxel and flavopiridol.

SECONDARY OBJECTIVES:

1. Determine the time to progression and overall survival of patients treated with this regimen.

2. Assess the toxicity of this regimen.

OUTLINE: This is a non-randomized, open-label, prospective study.

Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Non-Randomized Phase II Study of Alvocidib (Flavopiridol) in Combination With Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI #6366)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (docetaxel and alvocidib) Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: alvocidib; Given IV; Other Names: FLAVO flavopiridol HMR 1275 L-868275 ; Drug: docetaxel; Given IV; Other Names: RP 56976 Taxotere TXT

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate as Measured by RECIST Criteria [Up to 2 years]

   Objective response rate as measured by RECIST criteria

Secondary Outcome Measures

1. Time to Progression [Between the start of treatment until the criteria for progression are met, assessed up to 2 years]

   Will be computed using Kaplan-Meier methods.

2. Overall Survival [Between the start of treatment until patient death, assessed up to 2 years]

   Will be computed using Kaplan-Meier methods.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Evidence of metastatic disease

• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥ 10 mm with spiral CT scan

• The primary site is not a measurable lesion

• Documented progression with measurable metastatic disease including any 1 of the following criteria:

• Receiving adjuvant therapy for resected disease

• Receiving therapy for locally advanced disease

• Within 3 months of completing adjuvant therapy or therapy for locally advanced disease

• On 1 prior regimen in the metastatic setting

• No documented brain metastases

• Karnofsky performance status (PS) 80-100% OR ECOG PS 0-1

• WBC ≥ 2,500/mm³

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

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

• AST and ALT < 2.5 times ULN

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Alkaline phosphatase ≤ 5 times ULN

• No history of allergic reactions to compounds of similar chemical orbiological composition to flavopiridol

• No known allergy to docetaxel or medications formulated in polysorbate 80 (Tween 80)

• No uncontrolled diabetes

• No uncontrolled intercurrent illness including, but not limited to any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia or myocardial infarction within the past 6 months

• Rate-controlled atrial fibrillation stable for ≥ 6 months allowed

• Psychiatric illness or social situations that would limit compliance with study requirements

• Not pregnant or nursing

• Negative pregnancy test

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

• No peripheral neuropathy > grade 1

• No immune deficiency

• Atl east 2 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin C) and recovered

• At least 2 weeks since prior targeted therapy (e.g., antiangiogenic therapy [e.g., bevacizumab] or epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [e.g., erlotinib hydrochloride]) and recovered

• At least 4 weeks since prior radiation therapy

• No prior docetaxel or flavopiridol

• No other concurrent chemotherapy or investigational agents

• No other concurrent anticancer agents or therapies

• No concurrent commonly used vitamins, antioxidants, orherbal preparations or supplements

• Single-tablet multivitamin allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Eileen O'Reilly, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00331682
• Other Study ID Numbers: NCI-2012-01471; 05-136; MSKCC-05136; NCI-6366; CDR0000472413; R01CA067819
• First Posted: May 31, 2006
• Last Update Posted: May 28, 2014
• Last Verified: Nov 1, 2013

• Additional relevant MeSH terms: Pancreatic Neoplasms; Docetaxel; Alvocidib

Study Results

Participant Flow

Arm/Group Title	Docetaxel and Flavopiridol
Arm/Group Description	Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. alvocidib: Given IV docetaxel: Given IV
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Docetaxel and Flavopiridol
Arm/Group Description	Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. flavopiridol: Given IV docetaxel: Given IV
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (21.21320344)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 44.4%
>=65 years	5 55.6%
Sex: Female, Male (Count of Participants)
Female	6 66.7%
Male	3 33.3%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate as Measured by RECIST Criteria
Description	Objective response rate as measured by RECIST criteria
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel and Flavopiridol
Arm/Group Description	Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. flavopiridol: Given IV docetaxel: Given IV
Measure Participants	9
Stable Disease	3 33.3%
Progression of Disease	6 66.7%

2. Secondary Outcome

Title	Time to Progression
Description	Will be computed using Kaplan-Meier methods.
Time Frame	Between the start of treatment until the criteria for progression are met, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel and Flavopiridol
Arm/Group Description	Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. flavopiridol: Given IV docetaxel: Given IV
Measure Participants	9
Median (Full Range) [weeks]	8

3. Secondary Outcome

Title	Overall Survival
Description	Will be computed using Kaplan-Meier methods.
Time Frame	Between the start of treatment until patient death, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel and Flavopiridol
Arm/Group Description	Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. flavopiridol: Given IV docetaxel: Given IV
Measure Participants	9
Median (Full Range) [months]	4.2

Adverse Events

Arm/Group Title	Docetaxel and Flavopiridol
Arm/Group Description	Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. flavopiridol: Given IV docetaxel: Given IV
All Cause Mortality
	Docetaxel and Flavopiridol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel and Flavopiridol
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	2/10 (20%)	2
Cardiac disorders
Palpitations	1/10 (10%)	1
Gastrointestinal disorders
Ascites (non-malignant)	1/10 (10%)	1
Diarrhea	4/10 (40%)	4
Gastrointestinal disorder	1/10 (10%)	1
Anal hemorrhage	1/10 (10%)	1
Nausea	1/10 (10%)	1
Colonic obstruction	1/10 (10%)	1
Small intestinal obstruction	2/10 (20%)	2
Abdominal Pain	2/10 (20%)	2
Vomiting	2/10 (20%)	2
General disorders
Death not associated w/ CTCAE term-Disease Progression NOS	2/10 (20%)	2
Edema-visceral	1/10 (10%)	1
Fatigue	3/10 (30%)	3
Non-cardiac chest pain	1/10 (10%)	1
Investigations
Alanine aminotransferase increased	1/10 (10%)	1
Aspartate aminotransferase increased	1/10 (10%)	1
Alkaline phosphatase increased	1/10 (10%)	1
White blood cell decreased	4/10 (40%)	4
Lymphocyte count decreased	4/10 (40%)	4
Neutrophil count decreased	4/10 (40%)	4
Platelet count decreased	1/10 (10%)	1
Metabolism and nutrition disorders
Dehydration	2/10 (20%)	2
Hyperglycemia	2/10 (20%)	2
Hypoglycemia	1/10 (10%)	1
Hypophosphatemia	1/10 (10%)	1
Hyponatremia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/10 (10%)	1
Psychiatric disorders
Confusion	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/10 (10%)	1
Pleural effusion	1/10 (10%)	1
Vascular disorders
Thrombosis	3/10 (30%)	3
Other (Not Including Serious) Adverse Events
	Docetaxel and Flavopiridol
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Hemoglobin	3/9 (33.3%)	3
Gastrointestinal disorders
Constipation	1/9 (11.1%)	1
Diarrhea	4/9 (44.4%)	4
Dyspepsia	1/9 (11.1%)	1
Nausea	1/9 (11.1%)	1
Abdominal pain	1/9 (11.1%)	1
General disorders
Fatigue	5/9 (55.6%)	5
Non-cardiac chest pain	1/9 (11.1%)	1
Investigations
Alanine aminotransferase increased	1/9 (11.1%)	1
Alkaline phosphatase increased	2/9 (22.2%)	2
Blood bilirubin increased	1/9 (11.1%)	1
Cardiac troponin I increased	1/9 (11.1%)	1
Creatinine increased	1/9 (11.1%)	1
INR increased	1/9 (11.1%)	1
White blood cell decreased	6/9 (66.7%)	6
Lymphocyte count decreased	5/9 (55.6%)	5
Neutrophil count decreased	4/9 (44.4%)	4
Platelet count decreased	2/9 (22.2%)	2
Metabolism and nutrition disorders
Hypoalbuminemia	5/9 (55.6%)	5
Anorexia	1/9 (11.1%)	1
Hypocalcemia	1/9 (11.1%)	1
Hyperglycemia	9/9 (100%)	9
Hypoglycemia	3/9 (33.3%)	3
Hypophosphatemia	3/9 (33.3%)	3
Hypokalemia	1/9 (11.1%)	1
Hyponatremia	2/9 (22.2%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme	1/9 (11.1%)	1
Vascular disorders
Thrombosis	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.