S0916, MLN1202 in Treating Patients With Bone Metastases

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01015560
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 44
• Locations: 47
• Arm: 1
• Duration (Months): 33.1
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such MLN1202, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase II trial is studying how well MLN1202 works in treating patients with bone metastases.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific	Drug: anti-CCR2 monoclonal antibody MLN1202; Genetic: polymorphism analysis; Other: laboratory biomarker analysis	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the urinary n-telopeptide (uNTX) response to anti-CCR2 monoclonal antibody MLN1202 in patients with bone metastases.

Secondary

• To assess the feasibility of performing cross-disease site trials within the Southwest Oncology Group.

• To explore the effect of anti-CCR2 monoclonal antibody MLN1202 on markers of tumor cell proliferation, monocytes/macrophage trafficking, and osteoclast maturation.

• To estimate allele frequencies of defined SNPs occurring in the CCL2 and CCR2 genes in these patients.

OUTLINE: This is a multicenter study.

Patients receive anti-CCR2 monoclonal antibody MLN1202 IV over 1 hour on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity.

Patients undergo urine and blood sample collection at baseline and on days 15, 29, and 43 for correlative biomarker and polymorphism studies.

After completion of study treatment, patients are followed up for ≥ 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: S0916, A Phase II, Window Trial of the Anti-CCR2 Antibody MLN1202 in Patients With Bone Metastases
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment MLN1202 8mg/kg IV Days 1, 15, 29 given as 1 6 week cycle	Drug: anti-CCR2 monoclonal antibody MLN1202; Genetic: polymorphism analysis; Other: laboratory biomarker analysis

Outcome Measures

Primary Outcome Measures

1. uNTX Response Rate at 43 Days [43 days]

   Urinary n-telopeptide (uNTX) response is defined as a 25% reduction from baseline levels. Patients with missing response data were included as non-responders.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Radiographically documented metastases to the bone by bone scan, x-ray, CT scan, MRI, or PET scan within the past 42 days

• Documentation of progression of metastatic disease by serial scans is not required for study entry

• No untreated or progressive brain metastases

• History of brain metastases allowed provided they have been treated and remain controlled

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Must consent to urine and blood specimen submissions

• No concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with the study requirements

• No known hypersensitivity to anti-CCR2 monoclonal antibody MLN1202 or other recombinant human antibodies

PRIOR CONCURRENT THERAPY:

• At least 14 days since prior radiotherapy and recovered (≤ grade 1 from all related toxicities)

• At least 84 days since prior radionuclide therapy (e.g., strontium, samarium) and recovered (≤ grade 1 from all related toxicities)

• More than 14 days since prior investigational agents, chemotherapeutic agents, or other anticancer agents

• Concurrent bisphosphonate therapy for bone metastases allowed provided treatment was initiated ≥ 28 days before study entry

• No initiation of bisphosphonates during study treatment

• Concurrent hormonal therapy (e.g., anti-estrogens or anti-androgens) or stable doses of steroids for cancer allowed provided treatment was initiated > 14 days before study entry

• No concurrent G-CSF or other growth factor support

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Glendale Memorial Hospital Comprehensive Cancer Center	Glendale	California	United States	91204
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
3	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
4	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
5	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
6	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
7	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
8	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
9	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
10	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
11	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
12	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
13	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67905
14	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
15	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
16	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
17	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
18	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
19	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
20	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
21	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
22	CCOP - Wichita	Wichita	Kansas	United States	67214
23	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
24	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
25	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
26	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
27	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
28	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
29	University of New Mexico Cancer Center - South	Las Cruces	New Mexico	United States	88011
30	Grandview Hospital	Dayton	Ohio	United States	45405
31	Good Samaritan Hospital	Dayton	Ohio	United States	45406
32	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
33	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
34	CCOP - Dayton	Dayton	Ohio	United States	45420
35	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
36	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
37	Wayne Hospital	Greenville	Ohio	United States	45331
38	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
39	MedCentral - Mansfield Hospital	Mansfield	Ohio	United States	44903
40	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
41	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
42	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
43	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
44	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78209
45	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
46	Cancer Therapy and Research Center	San Antonio	Texas	United States	78229
47	University Hospital - San Antonio	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kenneth J. Pienta, MD, FACP, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT01015560
• Other Study ID Numbers: S0916; S0916; U10CA032102
• First Posted: Nov 18, 2009
• Last Update Posted: Aug 9, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Southwest Oncology Group: bone metastases; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Neoplasm Metastasis; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	MLN 1202
Arm/Group Description	MLN1202 8mg/kg IV Days 1, 15, 29 given as one 6-week cycle
Period Title: Overall Study
STARTED	44
Eligible and Analyzable	43
COMPLETED	41
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	MLN 1202
Arm/Group Description	MLN1202 8mg/kg IV Days 1, 15, 29 given as one 6-week cycle
Overall Participants	43
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	24 55.8%
Male	19 44.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.3%
Not Hispanic or Latino	30 69.8%
Unknown or Not Reported	12 27.9%
Race/Ethnicity, Customized (participants) [Number]
White	39 90.7%
Black	4 9.3%

Outcome Measures

1. Primary Outcome

Title	uNTX Response Rate at 43 Days
Description	Urinary n-telopeptide (uNTX) response is defined as a 25% reduction from baseline levels. Patients with missing response data were included as non-responders.
Time Frame	43 days

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients

Arm/Group Title	MLN 1202
Arm/Group Description	MLN1202 8mg/kg IV Days 1, 15, 29 given as one 6-week cycle
Measure Participants	43
Number (95% Confidence Interval) [percentage of participants]	14 32.6%

Adverse Events

Time Frame	Minimum of 30 days after the last dose of protocol therapy, or every 4 to 6 weeks until all protocol therapy-related toxicities resolve, return to baseline, or are deemed irreversible, whichever is longer.
Adverse Event Reporting Description	Only eligible and analyzable patients that were assessed for adverse events are included. One patient was not assessed for adverse events and is not included in this analysis.
Arm/Group Title	MLN 1202
Arm/Group Description	MLN1202 8mg/kg IV Days 1, 15, 29 given as one 6-week cycle
All Cause Mortality
	MLN 1202
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	MLN 1202
	Affected / at Risk (%)	# Events
Total	3/42 (7.1%)
Gastrointestinal disorders
Nausea	1/42 (2.4%)
Vomiting	1/42 (2.4%)
Injury, poisoning and procedural complications
Fracture	1/42 (2.4%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/42 (2.4%)
Vascular disorders
Hypertension	1/42 (2.4%)
Other (Not Including Serious) Adverse Events
	MLN 1202
	Affected / at Risk (%)	# Events
Total	30/42 (71.4%)
Blood and lymphatic system disorders
Anemia	10/42 (23.8%)
Gastrointestinal disorders
Diarrhea	3/42 (7.1%)
General disorders
Edema limbs	5/42 (11.9%)
Fatigue	15/42 (35.7%)
Investigations
Alanine aminotransferase increased	3/42 (7.1%)
Alkaline phosphatase increased	4/42 (9.5%)
CD4 lymphocytes decreased	4/42 (9.5%)
Creatinine increased	8/42 (19%)
White blood cell decreased	4/42 (9.5%)
Metabolism and nutrition disorders
Anorexia	3/42 (7.1%)
Hyperglycemia	10/42 (23.8%)
Musculoskeletal and connective tissue disorders
Bone pain	7/42 (16.7%)
Generalized muscle weakness	3/42 (7.1%)
Nervous system disorders
Peripheral sensory neuropathy	4/42 (9.5%)
Renal and urinary disorders
Urinary frequency	3/42 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/42 (7.1%)
Vascular disorders
Hot flashes	5/42 (11.9%)
Hypertension	5/42 (11.9%)

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.