Docetaxel Alone or in Combination With Vaccine to Treat Breast Cancer

NCT00179309 | Completed Phase 2 Results DMC

• 2 other identifiers: 05022905-C-0229
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

This study will test whether giving a combination of a vaccine together with docetaxel is more effective against breast cancer than docetaxel alone. The Food and Drug Administration has approved docetaxel to treat many cancers, including breast cancer. The vaccine consists of three parts: 1) a "priming vaccine" called PANVAC (PAN (all) VAC (vaccine)) trademark \[TM\]-V, which is made from vaccinia virus; 2) a "boosting vaccine" called PANVAC\[TM\]-F, made from fowlpox virus; and 3) sargramostim, or granulocyte macrophage colony stimulating factor (GM-CSF), a protein that may help boost the immune system. Human genes are inserted into the vaccinia and fowlpox viruses to cause production of carcinoembryonic antigen (CEA) and mucin 1 (MUC-1)-two proteins that are often produced by cancer cells and can be used as a target for the immune system to attack the cancer. Another type of deoxyribonucleic acid (DNA) is inserted to cause production of other proteins that enhance immune activity. Patients 18 years of age or older with metastatic breast cancer (disease that has spread beyond the original site) and whose cancer produces CEA or mucin 1 (MUC-1) protein may be eligible for this study. Patients must have antigen type human leukocyte antigen A2 (HLA-A2). They may have received adjuvant docetaxel treatment at least 3 months before entering this study, prior hormonal therapy and up to three chemotherapy regimens. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, and computerized tomography (CT) or magnetic resonance imaging scans. Participants are randomly assigned to one of two treatment groups - docetaxel alone or docetaxel plus vaccine - as follows: Docetaxel Alone All patients receive docetaxel. The drug is infused through a vein over 30 to 60 minutes once a week for 3 consecutive weeks with 1 week off drug. Patients also take dexamethasone 12 hours and 1 hour before and 12 hours after the docetaxel to help prevent fluid retention (edema) that docetaxel may cause. Docetaxel Plus Vaccine Participants receive the priming vaccination followed by monthly boosting vaccinations, along with the weekly docetaxel therapy. With every vaccination, patients also receive an injection of sargramostim to increase the number of immune cells at the vaccination site. Sargramostim injections are given the day of vaccination and daily for the next 3 days. All vaccine and sargramostim doses are given as injections under the skin, usually in the thigh. Patients are observed in the clinic for 1 hour after each injection. Patients have blood tests every four weeks to monitor drug side effects and before every vaccination to check blood counts. A bone scan or CT scan (or both) is done every 2 to 3 months to check the response to treatment. Patients may continue receiving treatment as long as their disease does not worsen and they can tolerate the treatment without significant side effects. Patients assigned to receive docetaxel alone whose disease progresses after 3 months on the drug may choose to receive the vaccine or come off the study to receive other treatment options. Patients are monitored with yearly telephone calls for up to 15 years.

Conditions

Breast Cancer

Keywords

CEA; MUC-1; Immunotherapy; GM-CSF; Vaccine; Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Time between the first day of treatment and disease progression. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions.

  19.7 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  80 months

Study Arms (2)

Arm I - PANVAC + docetaxel

EXPERIMENTAL

Patients receive vaccinia-carcinoembryonic antigen (CEA)- mucin-1 (MUC-1)- triad of costimulatory molecules (TRICOM) vaccine subcutaneously (SC) once and sargramostim, or granulocyte macrophage colony stimulating factor (GM-CSF) SC once daily for 4 days in week -2. Patients also receive fowlpox-CEA-MUC-1-TRICOM vaccine SC once and GM-CSF SC once daily for 4 days in weeks 1, 5, and 9. Patients also receive docetaxel intravenous (IV) over 30 minutes once weekly in weeks 1-3, 5-7, and 9-11. After week 12, patients with no disease progression continue with docetaxel once weekly for 3 weeks followed by 1 week of rest and fowlpox-CEA-MUC-1-TRICOM vaccine plus GM-CSF every 4 weeks until disease progression.

Drug: Docetaxel; Biological: PANVAC-V; Biological: PANVAC-F; Biological: Sargramostim

Arm II - Docetaxel alone

EXPERIMENTAL

Patients receive docetaxel as in arm I. After week 12, patients with disease progression discontinue docetaxel and receive vaccinia-carcinoembryonic antigen (CEA)- mucin 1(MUC-1)-triad of costimulatory molecules (TRICOM) vaccine, fowlpox-CEA-MUC-1-TRICOM vaccine, and sargramostim, or granulocyte macrophage colony stimulating factor (GM-CSF) as in arm I until further disease progression. Patients with no disease progression after week 12 continue with docetaxel as in arm I until disease progression.

Drug: Docetaxel

Interventions

Docetaxel DRUG

35 mg/m\^2 intravenous 30-60 minutes once a week for 3 consecutive weeks with 1 week off drug.

Also known as: Taxotere

Arm I - PANVAC + docetaxel; Arm II - Docetaxel alone

PANVAC-V BIOLOGICAL

2 x 10\^8 PFU

Arm I - PANVAC + docetaxel

PANVAC-F BIOLOGICAL

1 x 10\^9 PFU

Arm I - PANVAC + docetaxel

Sargramostim BIOLOGICAL

Given subcutaneously under the skin, usually in the thigh on the day of vaccination and daily for the next 3 days.

Also known as: GM-CSF

Arm I - PANVAC + docetaxel

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic Breast Cancer (either male or female) with evidence of metastatic disease (must have radiographic evidence of measurable disease) on computed tomography (CT) scan or X-ray, or evidence of evaluable disease on bone scan that is consistent with metastasis and a life expectancy of at least 4 months. Patients may have received unlimited prior hormonal therapy and chemotherapy.
• Histologically confirmed adenocarcinoma of the breast cancer confirmed in the Pathology Clinical Center at National Cancer Institute (NCI), (or National Naval Medical Center (NNMC)) or MD Anderson Pathology Department prior to starting this study. Note: However, if no pathologic specimen is available, patients may enroll with a clinical course consistent with breast cancer and a pathological documentation of the disease.
• years of age or greater.
• May have received docetaxel in the adjuvant setting at least 12 months prior to study entry.
• Able to understand and give informed consent.
• Able to avoid close household contact (close household contacts are those who share housing or have close physical contact) for at least two weeks after recombinant vaccinia vaccination with persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including human immunodeficiency virus (HIV) infection. We have vaccinated over 700 cancer patients and have reported no cases of either self inoculation or person to person transmission of the virus.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• Serum creatinine less than 1.5 times upper limits of normal (ULN) OR creatinine clearance on a 24 hour urine collection of greater than or equal to 60 mL/min, standard liver function tests (LFT) limitations for patients receiving docetaxel therapy include bilirubin within ULN and serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 1.5 times the ULN. If transaminases are greater than 1.5 times the ULN up to 2 times the ULN (as currently indicated), then alk phos should be less than 2.5 times the ULN. (Patients with renal abnormalities should be evaluated for creatinine clearance (CrCl) and interstitial abnormalities. A Cr Cl of greater than or equal to 60ml/min measured or calculated and proteinuria less than 1000mg per 24 hours are eligible unless explained by non-renal causes.)
• Recovered completely from any grade 3 or 4 reversible hematologic and non hematologic toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who most recently received cytotoxic therapy. Patients previously treated with mitomycin c or carboplatin will require a minimum of 6 weeks.
• Hematological eligibility parameters (within 16 days of starting therapy):
• Granulocyte count greater than or equal to1,500/mm\^3
• Platelet count greater than or equal to 100,000/mm\^3
• Hemoglobin (Hgb) greater than or equal to 8 Gm/dL
• Must agree to use effective birth control or abstinence during and for a period of 4 months after the last vaccination therapy.
• Patients whose tumors are estrogen receptor (ER) positive should have failed primary hormone therapy unless clinically indicated, i.e. in patients with visceral disease or symptomatic bone disease where up front chemotherapy is warranted. Patients who progressed or recurred following Trastuzumab (Herceptin) therapy if a patient is fluorescence in situ hybridization (FISH) positive or immunohistochemistry (IHC) 3+ positive for human epidermal growth factor receptor 2 (Her-2 neu). Those patients who have progressed on trastuzumab may continue to receive the drug by their referring physician. However, if trastuzumab has been discontinued at the time of enrolling on study, it cannot be resumed while a patient remains on study.

You may not qualify if:

• Patients should appear clinically stable (in the opinion of the principle investigator) to complete the full 3 month course of vaccination with an anticipated survival of 6 months or longer.
• No other active malignancies within the past 12 months (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.
• Patients with cardiovascular symptoms should be fully evaluated for signs and symptoms of cardiovascular disease and other standard evaluations including electrocardiogram (EKG), chest X-ray, cardiac enzymes, and echocardiogram as clinically indicated.
• Patients should have no evidence of being immunocompromised as listed below.
• Human immunodeficiency virus positivity due to the potential for decreased tolerance and risk for severe side effects
• Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity Patients with endocrine disease that is controlled by replacement therapy including thyroid disease and adrenal disease and vitiligo may be enrolled
• Concurrent use of systemic steroids, except for local (topical, nasal, or inhaled) steroid use
• History of allergy or untoward reaction to prior vaccination with vaccinia virus.
• Pregnant or breast-feeding women
• Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis
• Clinically active brain metastasis, or a history of seizures that have been active within one year
• Medical conditions, which, in the opinion of the investigators would jeopardize the patient or the integrity of the data obtained
• Prior docetaxel chemotherapy for metastatic disease
• Serious hypersensitivity reaction to egg products

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030-4096, United States

Location

Related Publications (6)

• Garnett CT, Schlom J, Hodge JW. Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res. 2008 Jun 1;14(11):3536-44. doi: 10.1158/1078-0432.CCR-07-4025.

  PMID: 18519787 BACKGROUND

• Gulley JL, Madan RA, Arlen PM. Enhancing efficacy of therapeutic vaccinations by combination with other modalities. Vaccine. 2007 Sep 27;25 Suppl 2(Suppl 2):B89-96. doi: 10.1016/j.vaccine.2007.04.091. Epub 2007 Jun 4.

  PMID: 17573164 BACKGROUND

• Arlen PM, Pazdur M, Skarupa L, Rauckhorst M, Gulley JL. A randomized phase II study of docetaxel alone or in combination with PANVAC-V (vaccinia) and PANVAC-F (fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229). Clin Breast Cancer. 2006 Jun;7(2):176-9. doi: 10.3816/CBC.2006.n.032. No abstract available.

  PMID: 16800982 BACKGROUND

• Huang J, Jochems C, Talaie T, Anderson A, Jales A, Tsang KY, Madan RA, Gulley JL, Schlom J. Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood. 2012 Oct 11;120(15):3030-8. doi: 10.1182/blood-2012-05-427799. Epub 2012 Aug 28.

  PMID: 22932804 BACKGROUND

• Gorodetska I, Samusieva A, Lahuta T, Ponomarova O, Socha O, Kozeretska I. Exploring New Frontiers: Alternative Breast Cancer Treatments Through Glycocalyx Research. Breast J. 2025 May 22;2025:9952727. doi: 10.1155/tbj/9952727. eCollection 2025.

  PMID: 40443562 DERIVED

• Heery CR, Ibrahim NK, Arlen PM, Mohebtash M, Murray JL, Koenig K, Madan RA, McMahon S, Marte JL, Steinberg SM, Donahue RN, Grenga I, Jochems C, Farsaci B, Folio LR, Schlom J, Gulley JL. Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in Patients With Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2015 Nov;1(8):1087-95. doi: 10.1001/jamaoncol.2015.2736.

  PMID: 26291768 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

The goal of this study was to get preliminary evidence of improved progression free survival with the combination compared with docetaxel alone and obtain data on which to plan a larger more definitive study in a more uniform patient population.

Results Point of Contact

• Title: Dr. James Gulley, M.D., Ph.D.
• Organization: National Cancer Institute, National Institutes of Health

gulleyj@mail.nih.gov

301-435-2956

Study Officials

• James L Gulley, M.D., Ph.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 15, 2005
• Study Start: September 1, 2005
• Primary Completion: February 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 15, 2014
• Results First Posted: June 27, 2013

Record last verified: 2014-06

Locations

US (2)