Fresolimumab and Radiotherapy in Metastatic Breast Cancer

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01401062
• Collaborator: University of California, Los Angeles (Other)
• Enrollment: 23
• Locations: 2
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 11.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to test safety of combining fresolimumab and local radiotherapy and to see if the combination can achieve tumor regression.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Fresolimumab; Radiation: Radiation Therapy	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fresolimumab and Radiotherapy in Metastatic Breast Cancer
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 (Fresolimumab 1 mg/kg) Fresolimumab is administered intravenously (i.v.) at a dose of 1 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2).	Drug: Fresolimumab; Other Names: GC1008 ; Radiation: Radiation Therapy
Experimental: Arm 2 (Fresolimumab 10 mg/kg) Fresolimumab is administered intravenously (i.v.) at a dose of 10 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2).	Drug: Fresolimumab; Other Names: GC1008 ; Radiation: Radiation Therapy

Outcome Measures

Primary Outcome Measures

1. Abscopal Response Rate [up to 20 weeks]

   Defined as the percentage of patients who have responses (complete or partial) outside the irradiated lesions. The abscopal response is assessed at 15 weeks, and confirmed minimum 4 weeks later. The abscopal response is evaluated based on immune-related response criteria (irRC) (Wolchok et al, 2009).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Biopsy-proven breast cancer, metastatic (persistent or recurrent).

• Failed ≥1 line of therapy (endocrine or chemotherapy) for metastatic disease.

• Min. 3 distinct metastatic sites, at least one measurable lesion which is at least 1 cm or larger in largest diameter.

• Must be ≥4 weeks since all of the following treatments (recovered from toxicity of prior treatment to ≤Grade 1, excluding alopecia):

• major surgery;

• radiotherapy;

• chemotherapy (≥6 weeks since therapy if a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab);

• immunotherapy;

• biotherapy/targeted therapies.

• 18 years of age.

• Life expectancy >6 months.

• Eastern Cooperative Oncology Group (ECOG) status 0 or 1.

• Adequate organ function including:

• Hemoglobin ≥10.0g/dL, absolute neutrophil count (ANC) ≥1,500/mm3, and platelets ≥100,000/mm3.

• Hepatic: Serum total bilirubin ≤1.5x upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if total bilirubin is ≤3.0mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2.5xULN. If patient has known liver metastases, ALT and/or AST ≤5xULN are allowed.

• Renal: creatinine clearance ≥60mL/min.

• Prothrombin (PT) and partial thromboplastin times (PTT) <ULN.

• Negative for hepatitis viruses B and C unless consistent with prior vaccination or prior infection with full recovery.

• Patients of childbearing potential must agree to use effective contraception while on study, and for ≥3 months after last treatment.

• Understand and sign written informed consent document. No consent by durable power of attorney.

Exclusion Criteria:

• Second malignancy - unless following curative intent therapy, has been disease free for ≥2 years with probability of recurrence <5%. Curatively treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are allowed.

• Concurrent cancer therapy.

• Uncontrolled central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or disease that causes or threatens neurologic compromise (e.g. unstable vertebral metastases).

• History of ascites or pleural effusions, unless successfully treated.

• Organ transplant, including allogeneic bone marrow transplant.

• Immunosuppressive therapy including:

• Systemic corticosteroid therapy, including replacement therapy for hypoadrenalism. Inhaled or topical corticosteroids are allowed (if therapy is <5 days and is limited to systemic steroids as antiemetics);

• Cyclosporine A, tacrolimus, or sirolimus.

• Investigational agents within 4 weeks prior to study enrollment (≥6 weeks if treatment was long-acting agent such as monoclonal antibody).

• Significant or uncontrolled medical illness, e.g. congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with remote history of asthma or active mild asthma may participate.

• Active infection, including unexplained fever (>38.5°C).

• Systemic autoimmune disease (e.g. systemic lupus erythematosus, active rheumatoid arthritis).

• Known allergy to any component of GC1008.

• Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or anti-coagulation therapy (including anti platelet agents i.e. aspirin, clopidogrel, ticlopidine, dipyridamole, other agents inducing long-acting platelet dysfunction). Patients with history of deep venous thrombosis are allowed if treated, completely resolved, and no treatment for >4months.

• Calcium >11.0mg/dL (2.75mmol/L) unresponsive or uncontrolled in response to standard therapy (e.g. bisphosphonates).

• Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems, including, but not limited to:

• Other serious non-malignancy-associated conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs;

• Conditions, psychiatric, substance abuse, or other, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study;

• Pregnant or nursing women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095-1714
2	New York University Langone Medical Center Cancer Center	New York	New York	United States	10016

Sponsors and Collaborators

• Weill Medical College of Cornell University
• University of California, Los Angeles

Investigators

• Principal Investigator: Silvia Formenti, M.D., NYU Langone Health

Study Documents (Full-Text)

None provided.

More Information

Publications

• Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT01401062
• Other Study ID Numbers: S11-00533; BC100481
• First Posted: Jul 25, 2011
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Weill Medical College of Cornell University: metastatic breast cancer; TGF-beta; fresolimumab; monoclonal antibody; radiation therapy; abscopal response
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	Arm 1 (Fresolimumab 1 mg/kg)	Arm 2 (Fresolimumab 10 mg/kg)
Arm/Group Description	Fresolimumab is administered intravenously (i.v.) at a dose of 1 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy	Fresolimumab is administered intravenously (i.v.) at a dose of 10 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy
Period Title: Overall Study
STARTED	11	12
COMPLETED	0	4
NOT COMPLETED	11	8

Baseline Characteristics

Arm/Group Title	Arm 1 (Fresolimumab 1 mg/kg)	Arm 2 (Fresolimumab 10 mg/kg)	Total
Arm/Group Description	Fresolimumab is administered intravenously (i.v.) at a dose of 1 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy	Fresolimumab is administered intravenously (i.v.) at a dose of 10 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy	Total of all reporting groups
Overall Participants	11	12	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 81.8%	7 58.3%	16 69.6%
>=65 years	2 18.2%	5 41.7%	7 30.4%
Sex: Female, Male (Count of Participants)
Female	11 100%	12 100%	23 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Asian or Pacific Islander	1 9.1%	3 25%	4 17.4%
Black, not of Hispanic-American Origin	3 27.3%	0 0%	3 13%
White, not of Hispanic-American origin	6 54.5%	8 66.7%	14 60.9%
Other/Unknown	1 9.1%	1 8.3%	2 8.7%

Outcome Measures

1. Primary Outcome

Title	Abscopal Response Rate
Description	Defined as the percentage of patients who have responses (complete or partial) outside the irradiated lesions. The abscopal response is assessed at 15 weeks, and confirmed minimum 4 weeks later. The abscopal response is evaluated based on immune-related response criteria (irRC) (Wolchok et al, 2009).
Time Frame	up to 20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 (Fresolimumab 1 mg/kg)	Arm 2 (Fresolimumab 10 mg/kg)
Arm/Group Description	Fresolimumab is administered intravenously (i.v.) at a dose of 1 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy	Fresolimumab is administered intravenously (i.v.) at a dose of 10 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy
Measure Participants	11	12
Count of Participants [Participants]	11 100%	12 100%

Adverse Events

Arm/Group Title	Arm 1 (Fresolimumab 1 mg/kg)		Arm 2 (Fresolimumab 10 mg/kg)
Arm/Group Description	Fresolimumab is administered intravenously (i.v.) at a dose of 1 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy		Fresolimumab is administered intravenously (i.v.) at a dose of 10 mg/kg on day 1 of weeks 0, 3, 6, 9 & 12 and radiation administered at 7.5 Gy/fraction in 3 fractions during weeks 1 (to lesion 1) and 7 (to lesion 2). Fresolimumab Radiation Therapy
All Cause Mortality
	Arm 1 (Fresolimumab 1 mg/kg)		Arm 2 (Fresolimumab 10 mg/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 (Fresolimumab 1 mg/kg)		Arm 2 (Fresolimumab 10 mg/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		3/12 (25%)
Cardiac disorders
atrial fibrillation	2/11 (18.2%)		0/12 (0%)
Endocrine disorders
Hypercalcemia	1/11 (9.1%)		1/12 (8.3%)
Immune system disorders
Dyspnea	0/11 (0%)		1/12 (8.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progression	2/11 (18.2%)		2/12 (16.7%)
Nervous system disorders
Cord compression	1/11 (9.1%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/11 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Arm 1 (Fresolimumab 1 mg/kg)		Arm 2 (Fresolimumab 10 mg/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)		8/12 (66.7%)
Blood and lymphatic system disorders
Thrombocytopenia	2/11 (18.2%)		0/12 (0%)
Anemia	1/11 (9.1%)		1/12 (8.3%)
Neutropenia	0/11 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Abdominal Pain- Severe	1/11 (9.1%)		0/12 (0%)
Nausea	1/11 (9.1%)		0/12 (0%)
General disorders
Fatigue	3/11 (27.3%)		2/12 (16.7%)
Investigations
Aspartate Aminotransferase Increased	3/11 (27.3%)		0/12 (0%)
Alkaline Phosphate Increased	2/11 (18.2%)		0/12 (0%)
alanine aminotransferase	1/11 (9.1%)		0/12 (0%)
INR	1/11 (9.1%)		0/12 (0%)
Elevated Bilirubin	1/11 (9.1%)		0/12 (0%)
Elevated Amylase	1/11 (9.1%)		0/12 (0%)
Elevated Lipase	1/11 (9.1%)		0/12 (0%)
Oliguria	1/11 (9.1%)		0/12 (0%)
PTT	0/11 (0%)		1/12 (8.3%)
Elevated AST	0/11 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
hypercalcemia	1/11 (9.1%)		1/12 (8.3%)
Hypercalcemia	1/11 (9.1%)		0/12 (0%)
Dehydration	1/11 (9.1%)		0/12 (0%)
Hyperglycemia	1/11 (9.1%)		0/12 (0%)
Hypoalbuminemia	1/11 (9.1%)		0/12 (0%)
Hypocalcemia	1/11 (9.1%)		1/12 (8.3%)
Hypokalemia	1/11 (9.1%)		0/12 (0%)
Anorexia	0/11 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Bilaterial Effusion	1/11 (9.1%)		0/12 (0%)
Lower Sacral Pain	1/11 (9.1%)		0/12 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease Progression	2/11 (18.2%)		2/12 (16.7%)
Nervous system disorders
Cord compression	1/11 (9.1%)		0/12 (0%)
Neuropathy	1/11 (9.1%)		0/12 (0%)
Neuropathy- Lower Extremities	1/11 (9.1%)		0/12 (0%)
Hepatic Encephalopathy	1/11 (9.1%)		0/12 (0%)
Reproductive system and breast disorders
Pain (under R breast)	1/11 (9.1%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/11 (0%)		1/12 (8.3%)
Pleural Effusion	0/11 (0%)		1/12 (8.3%)
Pneumonia	0/11 (0%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Spinal Edema	1/11 (9.1%)		0/12 (0%)
Cellulitis	1/11 (9.1%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.