Official Title: “Randomized Single Institution Pilot Study of Vaccinia-CEA (6D)-Tricomand Fowlpox CEA(6D)-Tricom With GM-CSF in Combination With Docetaxel in Patients With CEA-Bearing Cancers”

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.

Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow and peripheral blood. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy and sargramostim with docetaxel may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving vaccine therapy together with sargramostim and docetaxel works compared to vaccine therapy and sargramostim alone in treating patients with metastatic lung cancer or metastatic colorectal cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

OBJECTIVES: - Determine the recommended dose and schedule of docetaxel when given in combination with recombinant vaccinia-CEA-TRICOM vaccine, recombinant fowlpox-CEA-TRICOM vaccine, and sargramostim (GM-CSF), defined by best immune response with acceptable toxicity, in patients with carcinoembryonic antigen (CEA)-expressing metastatic lung or colorectal cancer. - Compare the effect of varying doses and schedules of docetaxel on CEA-specific T-cell immune responses by ELISPOT assay in patients treated with these regimens. - Compare objective antitumor response in patients treated with these regimens.

OUTLINE: This is a 2-part, randomized, pilot study. Patients are randomized to 1 of 6 treatment arms: arms I, II, and III in part I (lung cancer and colorectal cancer patients) and arms IV, V, and VI in part II (lung cancer patients only). Patients are stratified according to disease site and HLA-A2 positivity (positive vs negative). At least 6 of 10 patients must be HLA-A2 positive for each of the treatment arms. - Vaccinia-CEA-TRICOM vaccine (parts I and II): In all treatment arms, patients receive vaccinia-CEA-TRICOM vaccine intradermally on day 1 and sargramostim (GM-CSF) subcutaneously (SC) into the vaccine site on days 1-4. - Fowlpox-CEA-TRICOM vaccine and concurrent chemotherapy: - Part I (lung cancer and colorectal cancer patients): - Arm I: Three weeks after treatment with vaccinia-CEA-TRICOM vaccine, patients receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC into each vaccination site on days 1-4. - Arm II: Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as as in arm I and lower-dose docetaxel IV over 30 minutes on days 1 and 8. - Arm III: Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and standard-dose docetaxel IV over 30 minutes on days 1 and 8. - Part II (lung cancer patients only): - Arm IV: Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and full-dose docetaxel IV over 1 hour on day 1. - Arm V: Patients receive full-dose docetaxel IV over 1 hour on day 1, fowlpox-CEA-TRICOM vaccine SC on day 8, and GM-CSF SC into each vaccination site on days 8-11. - Arm VI: Patients receive full-dose docetaxel as in arm V, fowlpox-CEA-TRICOM vaccine SC on day 15, and GM-CSF SC into each vaccination site on days 15-18.

Treatment in all arms repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Patients who do not have significant disease progression or unacceptable toxicity after 4 courses of treatment may receive additional fowlpox-CEA-TRICOM vaccine and docetaxel according to the treatment arm on which they were enrolled at study entry.

Patients are followed every 6 months for 2 years and then annually for 13 years.

PROJECTED ACCRUAL: A total of 60 patients (10 per treatment arm) will be accrued for this study within 10 months.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine
• Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine
• Drug: sargramostim
• Procedure: biological therapy
• Procedure: chemotherapy
• Procedure: colony-stimulating factor therapy
• Procedure: cytokine therapy
• Procedure: non-specific immune-modulator therapy
• Procedure: recombinant viral vaccine
• Procedure: vaccine therapy

Primary Measures

• Change in immune response as assessed by T-cells monthly

DISEASE CHARACTERISTICS:

• Histologically confirmed lung OR colorectal cancer
• Incurable metastatic disease
• Currently available standard treatment not likely to offer a survival advantage or result in superior palliation
• Evaluable disease by radiograph
• Tumor must currently express carcinoembryonic antigen (CEA) by immunohistochemistry OR
• CEA ≥ 10 ng/mL at any point during disease course
• No clinically active brain metastases
• Part I only:
• Must have had first- and second-line treatment OR declined second-line treatment
• Patients with colon cancer must have had or have been offered treatment with oxaliplatin

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-1
• Life expectancy
• At least 4 months
• Hematopoietic
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hepatic
• Bilirubin normal
• Meets 1 of the following criteria:
• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) AND alkaline phosphatase normal
• SGOT and SGPT ≤ normal AND alkaline phosphatase ≤ 4.0 times ULN
• Hepatitis B and C negative by clinical history and physical exam
• Renal
• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• Proteinuria ≤ grade 1
• Cardiovascular
• No known or suspected history of impaired cardiac function as evidenced by baseline echocardiogram
• Pulmonary
• Adequate pulmonary function
• Immunologic
• No history or clinical evidence of immune deficiency or autoimmunity
• HIV negative
• No history of or concurrent diagnosis of any of the following:
• Altered immunodeficiency
• Eczema or other eczematoid skin disorders
• Acute, chronic, or exfoliative skin condition (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Addison's disease
• Hashimoto's thyroiditis
• Systemic lupus erythematosus
• Sjögren's syndrome
• Scleroderma
• Myasthenia gravis
• Goodpasture's syndrome
• Active Graves' disease
• No history of allergy or untoward reaction to prior vaccination with vaccinia virus
• No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No history of allergy to eggs or egg products
• Gastrointestinal
• No frequent vomiting or severe anorexia
• No inflammatory bowel disease
• No Crohn's disease
• No ulcerative colitis
• No active diverticulitis
• Neurologic
• Neuropathy ≤ grade 1 (sensory neuropathy)
• No uncontrolled seizure disorder
• No encephalitis
• No multiple sclerosis
• Other
• Must be maintaining a reasonable state of nutrition (≤ 10 % weight loss in the past month)
• Must be able to avoid close household contact (defined as sharing housing or having close physical contact) for at least 3 weeks after recombinant vaccinia vaccination with any of the following individuals:
• Individuals with active or a history of eczema or other eczematoid skin disorders or those with unresolved acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Pregnant or nursing women
• Children ≤ 5 years of age
• Immunodeficient or immunosuppressed individuals (by disease or therapy), including HIV infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• No other concurrent serious medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• No concurrent biologic therapy
• No other concurrent immunotherapy
• Chemotherapy
• See Disease Characteristics
• At least 6 weeks since prior nitrosoureas or mitomycin
• Prior docetaxel allowed (part I only)
• No prior docetaxel (part II only)
• No other concurrent chemotherapy
• Endocrine therapy
• No concurrent systemic steroids except for the following:
• Physiologic doses for systemic steroid replacement therapy
• Local (topical, nasal, or inhaled) steroid use
• No concurrent steroid eye drops
• Premedication prior to and after docetaxel
• No concurrent hormonal therapy
• Radiotherapy
• No prior radiotherapy to > 50 % of all nodal groups
• Surgery
• More than 21 days since prior major surgery
• No prior splenectomy
• Other
• Recovered from prior therapy
• At least 3-4 weeks since prior cytotoxic therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Lombardi Cancer Research Center

Overall Clinical Trial Officials and Contacts

John L. Marshall, MD Study Chair Lombardi Cancer Research Center  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00088933

Study ID Number: CDR0000377574

ClinicalTrials.gov Identifier: NCT00088933

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database