Biological Therapy in Treating Women With Stage IV Breast Cancer

NCT00027807 | Completed Phase 1 DMC

• 6 other identifiers: CDR0000069072P30CA0224532006-130RWMC-0635146WSU-010307M1FWSU-0312004412
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining different types of biological therapies may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining different biological therapies in treating women who have stage IV breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer; ductal breast carcinoma

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose

  The dose at which dose-limiting toxicity occurs is defined as that dose at which 2 or more of 6 patients at that dose level have their infusions stopped due to toxicities or receive less than 80% of the planned dose.

• Toxicity profile

  Months 1, 2, 5 and 11, then every 6 months

• Clinical responses

  Months: 1, 2, 5 and 11, then every 6 months

• Overall survival and progression-free survival

  The interval from the beginning of immunotherapy to the time of death or for progression free survival it is defined as the interval from the beginning of immunotherapy to progression

Secondary Outcomes (1)

• Immune changes

  1 (+ 7 days), 2 (+ 7 days), 5 months (+ 7 days), then every 6months (+ 7 days) (immune evaluations will also be performed after the 4th and 8th infusion of Her2Bi armed ATC and within 1week of the completion of HER2Bi armed ATC)

Study Arms (1)

Aldesleukin, Sargramostim & therapeutic autologous lymphocytes

EXPERIMENTAL

Peripheral blood mononuclear cells (PBMC) for the generation of ATC will be collected using 1 or 2 phereses to obtain 8-20 × 109 PBMC for T cell expansion. The PBMC will be activated with OKT3 and expanded in IL-2 to generate from 20-320 ×109 ATC during a maximum of 14 days of culture. Three patients will be treated at each dose level. The dose levels for each infusion are: 5, 10, 20, and 40 billion. Each patient will receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encounter toxicities related to armed ATC, the dose and administration will be modified as delineated per the protocol. The patients will also receive subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250μg/m2 twice per week) will given subcutaneously to start 3 days before the 1st armed ATC infusion and ending 7 days after the last dose of armed ATC.

Biological: Aldesleukin; Biological: Sargramostim; Biological: therapeutic autologous lymphocytes

Interventions

Aldesleukin BIOLOGICAL

Subcutaneous injections of IL-2 (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion.

Also known as: Proleukin ®, IL-2

Aldesleukin, Sargramostim & therapeutic autologous lymphocytes

Sargramostim BIOLOGICAL

GM-CSF Injections will be given SQ GM-CSF (250 μg/m2/twice weekly), to start 3 days before the first ATC infusion and ending 1 week after the last ATC infusion.

Also known as: LeukineTM, GM-CSF, Granulocyte-Macrophage Colony Stimulating Factor

Aldesleukin, Sargramostim & therapeutic autologous lymphocytes

therapeutic autologous lymphocytes BIOLOGICAL

The time for armed-ATC infusions will vary from patient to patient, but the dose of armed-ATC (up to 40 billion) will be given over 30 min.

Aldesleukin, Sargramostim & therapeutic autologous lymphocytes

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Phase I: * Histologically confirmed infiltrating ductal carcinoma of the breast * Metastatic disease * Clinically asymptomatic with non-life-threatening metastases allowed * Measurable or evaluable disease by radiograph, CT scan, MRI, nuclear medicine bone scan, or physical examination * No measurable disease allowed if tumor or metastasis has been removed or successfully treated prior to study * No rapidly progressive symptomatic disease affecting major organ systems (e.g., lungs and liver) * Stable or unstable disease for 3 months on hormonal therapy * Stable or unstable disease for at least 1 month after chemotherapy * No active brain metastases * Brain metastases previously treated with definitive radiotherapy and/or surgical resection allowed * Hormone receptor status: * Estrogen and progesterone receptor status known Phase II: * All Phase I criteria * HER2/neu overexpression (2+ or 3+) by immunohistochemistry * Prior trastuzumab (Herceptin) allowed if disease still overexpresses HER2/neu PATIENT CHARACTERISTICS: Age: * 18 and over Sex: * Female Menopausal status: * Not specified Performance status: * Karnofsky 70-100% OR * ECOG 0-2 Life expectancy: * At least 3 months Hematopoietic: * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 50,000/mm\^3 * Hemoglobin at least 8 g/dL Hepatic: * Bilirubin less than 1.5 times normal * SGOT less than 1.5 times normal Renal: * Creatinine no greater than 1.8 mg/dL * Creatinine clearance at least 60 mL/min * BUN no greater than 1.5 times normal Cardiovascular: * No myocardial infarction within the past year * No prior myocardial infarction with coronary symptoms requiring medication and/or depressed left ventricular function (LVEF less than 50% by MUGA) * No angina or coronary symptoms requiring medication and/or with depressed left ventricular function (LVEF less than 50% by MUGA) * No congestive heart failure requiring medical management * LVEF at least 50% at rest by MUGA * No uncontrolled hypertension (i.e., systolic blood pressure \[BP\] ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg) Pulmonary: * FEV1, DLCO, and FVC at least 50% predicted Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No other serious medical or psychiatric illness that would preclude study participation * No other prior or concurrent malignancy within the past 5 years except curatively treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any other curatively treated disease in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy: * See Disease Characteristics * Prior trastuzumab allowed for phase I Chemotherapy: * See Disease Characteristics * At least 4 weeks since prior chemotherapy Endocrine therapy: * See Disease Characteristics * Concurrent hormonal therapy for breast cancer must continue during study * No other concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes) Radiotherapy: * See Disease Characteristics Surgery: * See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Related Publications (5)

• Lum LG, Rathore R, Colvin GA, et al.: Targeting HER2/neu tumor cells with anti-CD3 activated T cells: clinical trials and trafficking studies. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-719, 2003.

  BACKGROUND

• Grabert RC, Smith JA, Tiggs JC, et al.: Anti-CD3 activated T cells (ATC) armed with OKT3 x Herceptin Bispecific antibody (Her2Bi), survive and divide, and secrete cytokines and chemokines after multiple cycles of killing directed at Her2/neu+ (Her2) tumor targets. [Abstract] Proceedings of the 94th Annual Meeting of the American Association of Cancer Research 44: A-2872, 565, 2003.

  RESULT

• Sen M, Wankowski DM, Garlie NK, Siebenlist RE, Van Epps D, LeFever AV, Lum LG. Use of anti-CD3 x anti-HER2/neu bispecific antibody for redirecting cytotoxicity of activated T cells toward HER2/neu+ tumors. J Hematother Stem Cell Res. 2001 Apr;10(2):247-60. doi: 10.1089/15258160151134944.

  PMID: 11359672 RESULT

• Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, Dizon DS, Kouttab N, Maizel A, Colaiace W, Liu Q, Rathore R. Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clin Cancer Res. 2015 May 15;21(10):2305-14. doi: 10.1158/1078-0432.CCR-14-2280. Epub 2015 Feb 16.

  PMID: 25688159 RESULT

• Park JA, Santich BH, Xu H, Lum LG, Cheung NV. Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release. J Immunother Cancer. 2021 May;9(5):e002222. doi: 10.1136/jitc-2020-002222.

  PMID: 33986124 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Ductal, Breast

Interventions

aldesleukin; Interleukin-2; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors

Study Officials

• Lawrence G. Lum, MD, DSc

  Barbara Ann Karmanos Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 7, 2001
• First Posted: January 27, 2003
• Study Start: October 1, 2001
• Primary Completion: September 1, 2010
• Study Completion: March 1, 2013
• Last Updated: February 17, 2016

Record last verified: 2016-02

Locations

US (1)