Erlotinib and Green Tea Extract (Polyphenon® E) in Preventing Cancer Recurrence in Former Smokers Who Have Undergone Surgery for Bladder Cancer

NCT00088946 | Completed Phase 2 DMC

• 2 other identifiers: CDR0000377681UCLA-0301091-03
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Green tea extract (Polyphenon® E) contains certain ingredients that may slow the growth of tumor cells and prevent the recurrence of cancer. Giving erlotinib or green tea extract after surgery may kill any remaining tumor cells and may prevent the recurrence of bladder cancer. PURPOSE: This randomized phase II trial is studying how well giving erlotinib together with green tea extract works in preventing cancer recurrence in former smokers who have undergone surgery for bladder cancer.

Conditions

Bladder Cancer

Keywords

transitional cell carcinoma of the bladder; stage 0 bladder cancer; stage I bladder cancer

Outcome Measures

Primary Outcomes (1)

• Evaluate the effects of a daily oral dose of polyphenon E, erlotinib, or placebo on subjects who are former smokers with a history of superficial bladder cancer on the bladder cancer recurrence rate at two years of any stage or grade of bladder cancer.

  2 years

Secondary Outcomes (4)

• To address the unmet need in medical management of superficial bladder cancer as an adjunct to standard of care.

  2 years

• Assess toxicities associated with daily oral dosing of polyphenon E or erlotinib in subjects at risk for bladder tumor recurrence and to define a safe and effective prevention dose of erlotinib.

  2 years

• Correlate the modulation of one or more biomarkers with recurrence of bladder cancer confirming the value as a surrogate endpoint biomarker for bladder cancer recurrence and/or progression.

  2 years

• To assess the risk of clinical bladder cancer progression in patients treated with polyphenon E, erlotinib or placebo.

  2 years

Study Arms (3)

Arm 1

EXPERIMENTAL

Polyphenon E plus erlotinib placebo daily for 12 months.

Dietary Supplement: Polyphenon E; Other: Erlotinib placebo

Arm 2

EXPERIMENTAL

Erlotinib and Polyphenon E placebo daily for 12 months.

Drug: erlotinib hydrochloride; Other: Polyphenon E

Arm 3

PLACEBO COMPARATOR

Erlotinib placebo and Polyphenon E placebo daily for 12 months.

Other: Erlotinib placebo; Other: Polyphenon E

Interventions

Polyphenon E DIETARY_SUPPLEMENT

4-200mg capsules PO daily for 12 months

Also known as: green tea extract

Arm 1

erlotinib hydrochloride DRUG

100 mg PO daily for 12 months

Also known as: Tarceva

Arm 2

Erlotinib placebo OTHER

identical to Erlotinib in look and appearance of dosing.

Arm 1; Arm 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be former smokers and have ceased smoking at study entry.
• Participants with any previous history of prior cancer diagnosis of Grade 1, 2, or 3, Ta or T1 papillary TCC, or CIS TCC, histologically confirmed, with a newly diagnosed or recurrent tumor within 6 months of accrual who are rendered disease free by standard of care. Patients with Grade 1 papillary tumors must meet at least one of the following additional criteria:
• multiple, synchronous tumors (\>2)
• a single tumor greater than 1 cm in size
• At study entry, patients must have no evidence of disease
• Participants may have been previously treated with intravesical therapy.
• Age\>18 years
• Transurethral resection of bladder tumor within 6 months prior to entry on to study
• Participants must have a signed written informed consent
• Agreement with complete abstinence from heterosexual intercourse or with the use of contraception during the treatment phase in women of childbearing potential
• Negative pregnancy test in women of childbearing potential
• Patients must have adequate bone marrow function at study entry (WBC\>3000, platelets\>100000/mm3, and hemoglobin\>10g/dl)
• Patients must have satisfactory renal and hepatic function, defined as plasma creatinine of \< 1.5mg/dl, total bilirubin \< 1.5, and AST/ALT \< 1.5 x the upper limit of normal
• Patients with evidence of obstructive lung disease as the etiology of a low diffusing capacity will still be eligible as long as the chest radiograph does not demonstrate interstitial changes

You may not qualify if:

• Prior chemotherapy or radiotherapy
• Prior (within 2 years) or concurrent malignancies, except non-melanomatous skin tumors or carcinoma in situ of the cervix
• Significant medical or psychiatric condition that would make the participant a poor protocol candidate
• TCC greater than or equal to T2 at most recent diagnosis
• Involvement of the upper urinary tract prior to or at the time of initial tumor resection
• Prior treatment with experimental drugs, high dose steroids, or with any other cancer treatment within 4 weeks prior to the first dose of study drug and for the duration of the study
• Positive pregnancy test at any time throughout the course of the study
• Normal consumption of greater than 5 cups of green tea daily
• Participants taking a known CYP 3A4 inducer or food products and medications known to be inhibitors or metabolized by CYP3A4/5 such as erythromycin, ketoconazole, etc. will be excluded since these drugs may be expected to result in altered exposure of Erlotinib
• ECOG performance status \> 1
• History of idiopathic pulmonary fibrosis or other interstitial lung disease
• Use of tricyclic antidepressants, including imipramine, dothiepin, and mianserin
• Use within the last 12 months of amiodarone, methotrexate, isoniazid, minocycline, or nitrofurantoin
• History of environmental or occupational metal dust or wood dust exposure
• History of connective tissue disease, including scleroderma, rheumatoid arthritis, Sjogren's Syndrome, or sarcoid

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Bladder Cancer Genitourinary Oncology, PC

Phoenix, Arizona, 85032, United States

Location

Veterans Affairs Medical Center - West Los Angeles

Los Angeles, California, 90073, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Santa Monica UCLA Medical Center

Santa Monica, California, 90404, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

polyphenon E; Tea; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Arie Belldegrun, MD, FACS

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: May 1, 2004
• Primary Completion: July 1, 2006
• Study Completion: July 1, 2006
• Last Updated: July 31, 2020

Record last verified: 2012-08

Locations

US (5)