A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03115801
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 47.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder) carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by intensity modulation radiation therapy/Image-guided radiation therapy (IMRT/IGRT) to maximally spare normal tissue), to one of their measurable lesions.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma; Metastatic Urothelial Carcinoma	Drug: Nivolumab; Drug: Atezolizumab; Radiation: Radiation & immunotherapy; Drug: Pembrolizumab	Phase 2

Detailed Description

The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder) carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by IMRT/IGRT to maximally spare normal tissue), to one of their measurable lesions. For patients assigned to the immunotherapy plus radiotherapy arm, immunotherapy treatment starts with the first radiotherapy fraction. Nivolumab will be given every 2 weeks for patients with metastatic renal cell cancer and atezolizumab/pembrolizumab will be given every 3 weeks for patients with metastatic urothelial cancer. Patients will be re-imaged at 9 week (year 1) or 12 week (years 2-3) intervals and evaluated for response (defined as an objective response of measurable metastatic sites outside the radiation field). This response will be evaluated with CT scans in non-irradiated measurable metastatic sites per RECIST version 1.1. Patients will continue to receive their respective immunotherapies for up to three years or until disease progression or until a dose limiting toxicity is reached.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Controlled Trial of Programmed Death -1/Programmed Death Ligand-1(PD-1/PDL-1) Axis Blockade Versus PD-1/PDL-1 Axis Blockade Plus Radiotherapy in Metastatic Genitourinary (Renal/Urothelial) Malignancies
• Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Oct 13, 2020
• Actual Study Completion Date: Oct 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A - immunotherapy alone Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64.	Drug: Nivolumab; Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.; Other Names: Immunotherapy ; Drug: Atezolizumab; Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.; Other Names: Tecentriq ; Drug: Pembrolizumab; Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.; Other Names: Keytruda
Active Comparator: Arm B - Radiation & immunotherapy Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days.	Drug: Nivolumab; Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.; Other Names: Immunotherapy ; Drug: Atezolizumab; Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.; Other Names: Tecentriq ; Radiation: Radiation & immunotherapy; Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Best Overall Response Rates of Immunotherapy Alone and of Immunotherapy Plus Radiotherapy (to a Single Metastatic Site). [from 96 weeks]

2. Assess the Difference in Participants for the Best Overall Response Between the Two Groups, Immunotherapy Alone and of Immunotherapy Plus Radiotherapy(to a Single Metastatic Site). [from 96 weeks]

Secondary Outcome Measures

1. Number of Participants With Progression Free Survival [from 96 weeks]

2. Number of Participants Who Experienced Toxicities Related to Immunotherapy and Immunotherapy Plus Radiotherapy Treatment Groups [from 96 weeks]

3. Participants Will be Measured for Overall Survival [from 96 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent document;

2. Any prior therapy is permitted except prior therapy with PD1/PDL1 inhibitor.

3. Histologic diagnosis of metastatic renal cell carcinoma or urothelial cancer;

4. Patients must have at least 2 distinct measurable metastatic sites at least 1 cm or larger in their largest diameter per RECIST 1.1

5. Patients must have adequate organ and marrow function as defined by initial laboratory tests.

6. At least 2 weeks since last chemotherapy and 4 weeks since last immunotherapy treatment.

7. Performance status Eastern cooperative oncology group (ECOG) 0-1

8. Men and women, ages > 18 years of age.

9. Life expectancy > 3 months

10. Stable brain metastases for at least 4 weeks and not steroid dependent

11. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Should a woman become pregnant or suspect she is pregnant while she is enrolled in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;

2. Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix;

3. Autoimmune/auto inflammatory disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis];

4. Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea;

5. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of PD-1/PDL-1 blocking antibody).

6. A history of prior treatment with PD-1/PDL-1blocking antibody;

7. Patients who have had immunotherapy within 4 weeks prior to entering the study.

8. Concomitant therapy with any of the following: interleukin -2 (IL-2), interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids;

9. Patients undergoing therapy with other investigational agents or other chemotherapy agents;

10. Women who:

11. are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after cessation of study drug, or

12. have a positive pregnancy test at baseline, or

13. are pregnant or breastfeeding

14. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medicine - New York Presbyterian Hospital	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

• Principal Investigator: Himanshu Nagar, M.D., Weill Cornell Medicine - New York Presbyterian Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 20, 2020

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03115801
• Other Study ID Numbers: 1606017369
• First Posted: Apr 14, 2017
• Last Update Posted: Sep 22, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Pembrolizumab; Nivolumab; Atezolizumab; Immunologic Factors

Study Results

Participant Flow

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
Period Title: Overall Study
STARTED	4	2
COMPLETED	1	0
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy	Total
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.	Total of all reporting groups
Overall Participants	4	2	6
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56.25	69	60.5
Sex: Female, Male (Count of Participants)
Female	1 25%	1 50%	2 33.3%
Male	3 75%	1 50%	4 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 50%	1 16.7%
Not Hispanic or Latino	3 75%	0 0%	3 50%
Unknown or Not Reported	1 25%	1 50%	2 33.3%
Region of Enrollment (participants) [Number]
United States	4 100%	2 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Best Overall Response Rates of Immunotherapy Alone and of Immunotherapy Plus Radiotherapy (to a Single Metastatic Site).
Time Frame	from 96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
Measure Participants	4	2
Count of Participants [Participants]	4 100%	2 100%

2. Primary Outcome

Title	Assess the Difference in Participants for the Best Overall Response Between the Two Groups, Immunotherapy Alone and of Immunotherapy Plus Radiotherapy(to a Single Metastatic Site).
Time Frame	from 96 weeks

Outcome Measure Data

Analysis Population Description

3 participants on ARM A and 2 participants on ARM B could not be analyzed because they were withdrawn from the trial for disease progression.

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
Measure Participants	1	0
Count of Participants [Participants]	1 25%	0 0%

3. Secondary Outcome

Title	Number of Participants With Progression Free Survival
Time Frame	from 96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
Measure Participants	4	2
Count of Participants [Participants]	1 25%	0 0%

4. Secondary Outcome

Title	Number of Participants Who Experienced Toxicities Related to Immunotherapy and Immunotherapy Plus Radiotherapy Treatment Groups
Time Frame	from 96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
Measure Participants	4	2
Count of Participants [Participants]	1 25%	1 50%

5. Secondary Outcome

Title	Participants Will be Measured for Overall Survival
Time Frame	from 96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Immunotherapy Alone	Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.	Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
Measure Participants	4	2
Count of Participants [Participants]	4 100%	2 100%

Adverse Events

Time Frame	2 years
Arm/Group Title	Arm A - Immunotherapy Alone		Arm B - Radiation & Immunotherapy
Arm/Group Description	Patients with Renal Cell carcinoma will receive Nivolumab alone Days 1, 15, 29, 43 and 57. Patients with Urothelial cancer will receive Atezolizumab or Pembrolizumab on Days 1, 22, 43 and 64. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Pembrolizumab: Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.		Radiation is given to one lesion, 30 Gy in 3 fractions of 10 Gy, every other day. On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Nivolumab: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57. Atezolizumab: Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64. Radiation & immunotherapy: Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.
All Cause Mortality
	Arm A - Immunotherapy Alone		Arm B - Radiation & Immunotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/2 (0%)
Serious Adverse Events
	Arm A - Immunotherapy Alone		Arm B - Radiation & Immunotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		1/2 (50%)
Blood and lymphatic system disorders
Hyperglycemia	0/4 (0%)	0	1/2 (50%)	1
Gastrointestinal disorders
Abdominal Pain	1/4 (25%)	3	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Hip Fracture	1/4 (25%)	3	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea on Exertion	1/4 (25%)	3	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A - Immunotherapy Alone		Arm B - Radiation & Immunotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		1/2 (50%)
Blood and lymphatic system disorders
Neutropenia	1/4 (25%)	1	0/2 (0%)	0
Elevated Alkaline Phosphate	0/4 (0%)	0	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
Back Pain	1/4 (25%)	1	0/2 (0%)	0
Intermittent discomfort in the right buttock	1/4 (25%)	1	0/2 (0%)	0

Limitations/Caveats

The clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.

More Information

Certain Agreements

All Principal Investigators ARE 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.