Vaccine Therapy and Sargramostim With or Without Docetaxel in Treating Patients With Metastatic Lung Cancer or Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This randomized phase I trial studies the side effects, best way to give, and best dose of docetaxel when given together with vaccine therapy and sargramostim in treating patients with metastatic lung cancer or metastatic colorectal cancer. 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.

Detailed Description
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OBJECTIVES: I. 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. II. 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. III. 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 1: 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 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.

Official Title
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Randomized Single Institution Pilot Study of Vaccinia-CEA(6D)-TRICOM and Fowlpox-CEA(6D)-TRICOM With GM-CSF in Combination With Docetaxel in Patients With CEA-Bearing Cancers

Conditions
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Extensive Stage Small Cell Lung Cancer, Recurrent Colon Cancer, Recurrent Non-small Cell Lung Cancer, Recurrent Rectal Cancer, Recurrent Small Cell Lung Cancer, Stage IV Colon Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Rectal Cancer

Intervention / Treatment
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* Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine
* Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine
* Drug: docetaxel
* Drug: sargramostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Must have had first- and second-line treatment OR declined second-line treatment (part I only) Patients with colon cancer must have had or have been offered treatment with oxaliplatin (part I only) ECOG 0-1 Life expectancy of at least 4 months Absolute neutrophil count >= 1,500/mm^3 WBC >= 3,000/mm^3 Platelet count >= 100,000/mm^3 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 Creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 mL/min Proteinuria =< grade 1 No known or suspected history of impaired cardiac function as evidenced by baseline echocardiogram Adequate pulmonary function 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) 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 No frequent vomiting or severe anorexia No inflammatory bowel disease No Crohn's disease No ulcerative colitis No active diverticulitis Neuropathy =< grade 1 (sensory neuropathy) No uncontrolled seizure disorder No encephalitis No multiple sclerosis 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 individuals with active or a history of eczema or other eczematoid skin disorders 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 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) 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: 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 No concurrent biologic therapy No other concurrent immunotherapy 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 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 No prior radiotherapy to > 50 % of all nodal groups More than 21 days since prior major surgery No prior splenectomy Recovered from prior therapy At least 3-4 weeks since prior cytotoxic therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine<br>* Given intradermally<br>* Other names: rF-CEA(6D)TRICOM;Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine<br>* Given intradermally<br>* Other names: rV-CEA(6D)-TRICOM;Drug: sargramostim<br>* Given subcutaneously<br>* Other names: Prokine;|
| Experimental: Arm II<br>Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and lower-dose docetaxel IV over 30 minutes on days 1 and 8. | Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine<br>* Given intradermally<br>* Other names: rF-CEA(6D)TRICOM;Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine<br>* Given intradermally<br>* Other names: rV-CEA(6D)-TRICOM;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;Drug: sargramostim<br>* Given subcutaneously<br>* Other names: Prokine;|
| Experimental: Arm III<br>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. | Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine<br>* Given intradermally<br>* Other names: rF-CEA(6D)TRICOM;Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine<br>* Given intradermally<br>* Other names: rV-CEA(6D)-TRICOM;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;Drug: sargramostim<br>* Given subcutaneously<br>* Other names: Prokine;|
| Experimental: Arm IV<br>Patients receive fowlpox-CEA-TRICOM vaccine and GM-CSF as in arm I and full-dose docetaxel IV over 1 hour on day 1. | Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine<br>* Given intradermally<br>* Other names: rF-CEA(6D)TRICOM;Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine<br>* Given intradermally<br>* Other names: rV-CEA(6D)-TRICOM;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;Drug: sargramostim<br>* Given subcutaneously<br>* Other names: Prokine;|
| Experimental: Arm V<br>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. | Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine<br>* Given intradermally<br>* Other names: rF-CEA(6D)TRICOM;Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine<br>* Given intradermally<br>* Other names: rV-CEA(6D)-TRICOM;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;Drug: sargramostim<br>* Given subcutaneously<br>* Other names: Prokine;|
| Experimental: Arm VI<br>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. | Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine<br>* Given intradermally<br>* Other names: rF-CEA(6D)TRICOM;Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine<br>* Given intradermally<br>* Other names: rV-CEA(6D)-TRICOM;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;Drug: sargramostim<br>* Given subcutaneously<br>* Other names: Prokine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor response rate defined as the number of patients in each arm achieving a complete or partial response or stable disease divided by the total number of patients on each arm measured according to standard RECIST guidelines |  | Up to 6 years | 
| Immune response defined as the numbers of patients who achieve an ELISPOT result of 1/30,000 or higher divided by the number of HLA-A2 positive individuals for each treatment arm | The actual ELISPOT will be recorded for each individual and will be presented graphically. | Up to 6 years | 
| Number of patients experiencing each of the toxicities by grade for each treatment arm |  | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average quantity of circulating CEA cells determined by quantitative real time RT-PCR | The impact of the combination therapy on CCC will be presented graphically with descriptive statistics. Will be plotted for each time point by each treatment group. | Up to 6 years |