S1200: Acupuncture, Sham Acupuncture, or Wait List for Joint Symptoms Related to Aromatase Inhibitors in Pts W/Early-Stage Breast Cancer

Sponsor

Southwest Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT01535066

Collaborator

National Cancer Institute (NCI) (NIH), National Center for Complementary and Integrative Health (NCCIH) (NIH)

226

Enrollment

Locations

Arms

75.1

Actual Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Acupuncture may help relieve joint pain.

PURPOSE: This randomized phase III trial studies acupuncture to see how well it works compared to sham acupuncture or waitlist in treating patients with joint pain related to aromatase inhibitors in patients with early-stage breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Pain	Procedure: acupuncture therapy Procedure: sham acupuncture	N/A

Detailed Description

OBJECTIVES:

Primary

To determine whether true acupuncture administered twice weekly for 6 weeks (8-12 sessions) compared to sham acupuncture and waitlist control causes a significant reduction in joint pain related to aromatase inhibitors (AIs) in women with early-stage breast cancer as measured by the Brief Pain Inventory-Short Form (BPI-SF) worst pain score at 6 weeks.

Secondary

To investigate the effects of true acupuncture administered twice weekly for 6 weeks (8-12 sessions) followed by 6 weekly treatments (4-6 sessions) of maintenance (12-18 sessions total over 12 weeks) compared to sham acupuncture and waitlist control in this study population; the evaluations at 12 and 24 weeks are to determine the benefit of additional 6 weekly acupuncture treatments for maintenance and to determine the durability of response after stopping acupuncture, respectively; the evaluation at 52 weeks is to determine the long-term effects of acupuncture and adherence to AIs.
To evaluate the effects of acupuncture on the BPI-SF worst pain, worst stiffness, pain severity, and pain-related interference scores at 6, 12, 16, 20, 24, and 52 weeks.
To evaluate the effects of acupuncture on Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (pain, stiffness, and function) for the hips and knees at 6, 12, 24, and 52 weeks.
To evaluate the effects of acupuncture on Modified-Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) (pain, stiffness, and function) at 6, 12, 24, and 52 weeks.
To evaluate the effects of acupuncture on the PROMIS Pain Impact-Short Form (PROMIS PI-SF) at 6, 12, 24, and 52 weeks.
To evaluate the effects of acupuncture on quality of life (QOL) as assessed by the Functional Assessment of Cancer Therapy-Endocrine Subscales (FACT-ES) at 6, 12, 24, and 52 weeks.
To evaluate the effects of acupuncture on functional testing with grip strength and "Timed Get Up and Go" (TGUG) test at 6, 12, 24, and 52 weeks.
To evaluate the effects of acupuncture on analgesic and opioid use at 2, 4, 6, 12, 16, 20, 24, and 52 weeks.
To evaluate the effects of acupuncture on self-reported AI adherence at 12, 24, and 52 weeks.
To assess AI adherence via urine AI metabolites at baseline, 24, and 52 weeks.
To evaluate the effects of acupuncture on serum hormones (estradiol, FSH, LH) and inflammatory biomarkers (serum TNFα, IL-6, IL-12, CRP, and urine c-telopeptides of Type II collagen (CTX-II) at 6, 12, and 24 weeks. (Exploratory)
To evaluate whether polymorphisms in CYP19A1 aromatase gene predict severity of AI-related joint symptoms. (Exploratory)
To assess the safety and tolerability of acupuncture in this study population.

OUTLINE: This is a multicenter study. Patients are stratified according to study site. Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive acupuncture twice weekly for 6 weeks and then once weekly for 6 weeks.
Arm II: Patients receive sham acupuncture twice weekly for 6 weeks and then once weekly for 6 weeks.
Arm III: Patients are assigned to a waiting list for 12 weeks. Patients complete the Brief Pain Inventory-Short Form (BPI-SF), the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, the Modified-Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the PROMIS Pain Impact-Short Form (PROMIS PI-SF), the FACT-ES Trial Outcome Index, and the Aromatase Inhibitor Usage Form questionnaires at baseline and at 6, 12, 24 and 52 weeks.

Patients undergo blood sample collection at baseline and at 6, 12, and 24 weeks for serum hormones (estradiol, FSH, LH) levels, inflammatory markers (TNFα, IL-6, IL-12, CRP), and DNA analysis. Urine samples are also collected at baseline and at 24 and 52 weeks for c-telopeptides of Type II collagen and aromatase inhibitor metabolites analysis.

After completion of study treatment, patients are followed up at 24 and 52 weeks.

Study Design

Study Type:

Interventional

Actual Enrollment :

226 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Participant)

Primary Purpose:

Supportive Care

Official Title:

Randomized Blinded Sham- and Waitlist-Controlled Trial of Acupuncture for Joint Symptoms Related to Aromatase Inhibitors in Women With Early Stage Breast Cancer

Actual Study Start Date :

Mar 27, 2012

Actual Primary Completion Date :

Jun 15, 2017

Actual Study Completion Date :

Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive acupuncture therapy twice weekly for 6 weeks and then once weekly for 6 weeks.	Procedure: acupuncture therapy Receive acupuncture
Sham Comparator: Arm II Patients receive sham acupuncture twice weekly for 6 weeks and then once weekly for 6 weeks.	Procedure: sham acupuncture Receive sham acupuncture
No Intervention: Arm III Patients are assigned to a waiting list for 12 weeks with standard follow-up care.

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive acupuncture therapy twice weekly for 6 weeks and then once weekly for 6 weeks.

Procedure: acupuncture therapy

Receive acupuncture

Sham Comparator: Arm II

Patients receive sham acupuncture twice weekly for 6 weeks and then once weekly for 6 weeks.

Procedure: sham acupuncture

Receive sham acupuncture

No Intervention: Arm III

Patients are assigned to a waiting list for 12 weeks with standard follow-up care.

Outcome Measures

Primary Outcome Measures

Decrease of joint pain associated with the use of AIs as measured by BPI-SF [6 weeks]

Secondary Outcome Measures

Benefit of acupuncture maintenance as assessed by BPI-SF, WOMAC, M-SACRAH, PROMIS PI-SF, FACT-ES, and TGUG [6, 12, 16, 20, and 24 weeks]
Durability of response as assessed by BPI-SF, WOMAC, M-SACRAH, PROMIS PI-SF, FACT-ES, and TGUG [52 weeks.]
Long-term effects of acupuncture as assessed by BPI-SF, WOMAC, M-SACRAH, PROMIS PI-SF, FACT-ES, and TGUG [52 weeks]
Analgesic and opioid use [2, 4, 6, 12, 16, 20, 24, and 52 weeks]
AI adherence [12, 24, and 52 weeks]
Safety and tolerability of acupuncture [2, 4, 6, 12, 16, 20, 24, and 52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Patients must be women with histologically confirmed primary invasive carcinoma of the breast (Stage I, II, or III) with no evidence of metastatic disease (M0); patients must have undergone modified radical mastectomy or breast-sparing surgery; patients must have recovered from all side-effects of the surgery
Patients must be positive for estrogen receptor (ER) and/or progesterone receptor (PgR) as determined by institutional standard
Patients must currently be taking a third-generation aromatase inhibitor (AI) - anastrozole, letrozole, or exemestane for at least the previous 90 days prior to registration with plans to continue for at least an additional 1 year after registration; patients may have switched AIs provided that they have been on a stable dose for at least 90 days; concurrent trastuzumab (Herceptin) is allowed
Patients must have completed the S1200 Brief Pain Inventory-Short Form (BPI-SF) within 14 days prior to registration; patients must have a worst pain score of at least 3 on the Brief Pain Inventory (item #2) that has started or increased since starting AI therapy
Patients must be willing to submit blood and urine samples for serum hormones (estradiol, FSH, LH), inflammatory biomarkers (serum TNFα, IL-6, IL-12, CRP and urine CTX-II), urine AI metabolites, and DNA analysis (CYP19A1), and must be given the option to consent to use of remaining specimens for future translational medicine studies; baseline samples must be obtained prior to beginning intervention

PATIENT CHARACTERISTICS:

Patients must be postmenopausal, as defined by at least one of the following:
≥ 12 months since the last menstrual period
Prior bilateral oophorectomy
Current use of a gonadotropin-releasing hormone (GnRH) agonist
Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND follicle-stimulating hormone (FSH) values consistent with the institutional normal values for the postmenopausal state; if patient is under the age of 55, FSH levels must be obtained within 28 days prior to registration
Patients must have a Zubrod performance status of 0 to 1
Patients must not have a severe bleeding disorder
Patients must not have concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including: inflammatory arthritis (e.g., rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis, polymyalgia rheumatica), gout, episodes of acute monoarticular arthritis clinically consistent with pseudogout, Paget disease affecting the study joint (knees/hands), a history of septic arthritis or avascular necrosis or intra-articular fracture of the study joint, Wilson disease, hemochromatosis, alkaptonuria, or primary osteochondromatosis
Patients must not have a history of bone fracture or surgery of the afflicted knees and/or hands within 6 months prior to registration
Patients must not have a history of illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the patient
Patients must be able to complete study questionnaires in English or Spanish
No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ [DCIS], adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for > 5 years

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Patients must not have had prior acupuncture treatment within the past 12 months or for AI-induced joint symptoms at any time
Patients must not be on narcotics within 14 days of registration
Patients must not have received oral corticosteroids, intramuscular corticosteroids, or intra-articular steroids within 28 days prior to registration
Patients must not have received topical analgesics (e.g., capsaicin preparations) or any other analgesics (e.g., opiates or tramadol, with the exception of nonsteroidal anti-inflammatory drugs [NSAIDs] and acetaminophen) within 14 days prior to registration
Patients must not have received or implemented any other medical therapy, alternative therapy, or physical therapy for the treatment of joint pain/stiffness within 28 days prior to registration; therapeutic massage is allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
2	Kaiser Permanente, Fremont	Fremont	California	United States	94538
3	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	Kaiser Permanente-Oakland	Oakland	California	United States	94611
5	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
6	Kaiser Permanente-Richmond	Richmond	California	United States	94801
7	Kaiser Permanente-Roseville	Roseville	California	United States	95661
8	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
9	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
10	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
11	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
12	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
13	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
14	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
15	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
16	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
17	Kaiser Permanente-Stockton	Stockton	California	United States	95210
18	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
19	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
20	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
21	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
22	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
23	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
24	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
25	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
26	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
27	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
28	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
29	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
30	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
31	Munson Medical Center	Traverse City	Michigan	United States	49684
32	Columbia University Medical Center	New York	New York	United States	10032
33	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
34	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
35	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
36	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29605
37	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina	United States	29605
38	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
39	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
40	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina	United States	29615
41	Greenville Health System Cancer Institute-Greer	Greer	South Carolina	United States	29650
42	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina	United States	29672
43	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
44	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
45	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
46	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
47	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686