Chemokine-Modulatory Regimen for Recurrent Resectable Colorectal Cancer

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01545141
• Collaborator: AIM ImmunoTech Inc. (Industry)
• Enrollment: 15
• Location: 1
• Arms: 4
• Duration (Months): 54.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Determine the safety of a combination of IFN, celecoxib, and rintatolimod for patients with recurrent colorectal cancer. This will also test whether the above combination can help the immune system to fight the tumors. The results will allow the investigators to determine the "preferred" combination for subsequent extended studies.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal	Drug: Chemokin Modulatory Regimen (5 MU/m2); Drug: Chemokin Modulatory Regimen (10 MU/m2); Drug: Chemokin Modulatory Regimen (20 MU/m2)	Phase 1/Phase 2

Detailed Description

A previously-demonstrated correlation between the density of CRC-infiltrating effector T cells and long-term outcomes (Galon et al., 2006; Pages et al., 2005) has been established. In preclinical ex vivo studies performed using explants of resected metastatic CRC, the combination of IFNα with nonselective or COX2-selective inhibitors of prostaglandin synthesis resulted in elevated production of the effector T cell-attracting chemokines CXCL10 and CCL5. This was associated with concomitant suppression of the intratumoral expression of CCL22, a Treg-attracting chemokine (Muthuswamy et al 2008 Canc Res, and Muthuswamy et al, submitted to Canc Res 2011). However, in a subset of patients, the optimal results, particularly with regard to CCL5 induction, required additional stimulation by a third agent, poly-I:C (a toll-like receptor -TLR Ligand).

Therefore, the investigators seek to establish the safety profile of a novel chemokine regimen consisting of IFN, celecoxib and poly-I:C. The investigators also hypothesize that the proposed neoadjuvant chemokine modulation treatment in recurrent CRC patients undergoing tumor resection may increase the density of tumor infiltrating lymphocytes (TILS).

In addition, treatment in the neoadjuvant setting will allow a comparative analysis of the effect of chemokine modulation on the local recruitment of effector-type T cells and the de-recruitment of Treg within resected tumor tissues; helping to determine the "preferred" chemokine-modulating regimen for subsequent extended studies. Such prospective studies will focus on using combinations of chemokine modulation and cancer vaccines in patients with CRC. The investigators have, for example, recently observed that αDC1, a new type of DC vaccine (Kalinski and Okada, 2010; Mailliard et al., 2004) is particularly effective in inducing the effector pathway of T cells differentiation. This was manifested by the induction of tumor-killing function and the induction of effector-type chemokine receptors (CXCR3 and CCR5) (Kalinski and Okada, 2010; Watchmaker et al., 2010). Combining the αDC1 vaccine to a safe, tolerable and efficacious CKM regimen may hold promise for patients with poor prognostic CRC.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase 1/2 Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Apr 8, 2016
• Actual Study Completion Date: Apr 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Surgery only Surgical resection only, performed as standard of care for the disease
Experimental: Chemokin Modulatory Regimen (5 MU/m2) Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days	Drug: Chemokin Modulatory Regimen (5 MU/m2); Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.; Other Names: Celebrex INTRON A Interferon-alpha 2b IFN-alpha Ampligen rintatolimod
Experimental: Chemokin Modulatory Regimen (10 MU/m2) Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 10 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days	Drug: Chemokin Modulatory Regimen (10 MU/m2); Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery; Other Names: Celebrex INTRON A Interferon-alpha 2b IFN-alpha Ampligen rintatolimod
Experimental: Chemokin Modulatory Regimen (20 MU/m2) Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days	Drug: Chemokin Modulatory Regimen (20 MU/m2); Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery; Other Names: Celebrex INTRON A Interferon-alpha 2b IFN-alpha Ampligen rintatolimod

Outcome Measures

Primary Outcome Measures

1. Change in the Number of Tumor-infiltrating CD8+ Cells. [Day of surgery: day 8-10]

   This will be assessed by the increase in the total number of tumor-infiltrating CD8+ T cells in the resected, recurrent CRC lesions (measured as the ratio between the CD8 mRNA message and the expression of the housekeeping gene HPRT), comparing Arm A and Arm B.

Secondary Outcome Measures

1. Treatment Related Adverse Events [1 week]

   The number of adverse events experienced within 1 week of treatment. This was completed for the Phase II portion of the study.

Eligibility Criteria

Criteria

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

Inclusion:

• Recurrent and/or metastatic resectable colorectal cancer, including disease within the abdomen and pelvis with no evidence of extra-abdominal metastases. Isolated resectable pulmonary metastasis are allowable in the absence of intra-abdominal metastasis. Intra-abdominal disease includes: isolated hepatic metastasis/metastases (see next inclusion criteria point), isolated peritoneal metastasis, peritoneal carcinomatosis (including patients undergoing cytoreductive surgery alone or in combination with hyperthermic intraperitoneal chemoperfusion - HIPEC), or a combination of hepatic and extrahepatic metastasis.

• Patients with isolated hepatic metastasis must satisfy a Clinical Risk Score of 3 or higher (see Appendix C)

• Eligible patients are expected to have a complete resection based on preoperative imaging. Any patient not found to be able to have complete resection will not be eligible for this study.

• No chemotherapy, radiotherapy, major surgery, or biologic therapy within 3 weeks of protocol treatment

• An ECOG performance status of 0, 1, or 2.

• Age equal to 18 years or older.

• Must have normal organ and marrow function as defined below:

• Platelet ≥ 75,000/µL

• Hemoglobin ≥ 9.0 g/dL

• Hematocrit ≥ 27.0%

• Absolute Neutrophil Count (ANC) ≥ 1500/µL

• Creatinine < institutional upper limit of normal (ULN) OR

• Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels greater than ULN

• Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN)

• AST(SGOT) and ALT(SGPT) ≤ 2.5 X institutional upper limit of normal (ULN)

• Serum amylase and lipase within normal limits.

• Patient must be able to understand and be willing to sign a written informed consent document.

Exclusion:

• Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment.

• Patients with active autoimmune disease or history of transplantation.

• Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening.

• Patients with comorbid medical conditions that render them unfit for surgery.

• Metastatic or recurrent disease that is deemed partially resectable or unresectable based on preoperative imaging.

• Metastatic disease outside the confines of the abdomen, pelvis and thorax (e.g bone, brain)

• Cardiac risk factors including:

• Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent

• Patients with a New York Heart Association classification of III or IV (Appendix

• History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years. Patients with ulceration, bleeding or perforation in the lower bowel are not excluded.

• Prior allergic reaction or hypersensitivity to sulfonamides, celecoxib, or NSAIDs.

• Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Roswell Park Cancer Institute
• AIM ImmunoTech Inc.

Investigators

• Principal Investigator: Amer H Zureikat, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT01545141
• Other Study ID Numbers: 10-131; 10-131
• First Posted: Mar 6, 2012
• Last Update Posted: Sep 9, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Roswell Park Cancer Institute: metastatic; recurrent; peritoneal metastasis; cytoreductive surgery; hyperthermic intraperitoneal chemoperfusion; HIPEC; hepatic metastasis; extrahepatic metastasis; vaccine
• Additional relevant MeSH terms: Colorectal Neoplasms; Interferons; Interferon-alpha; Interferon alpha-2; Interferon-alfa-1b; poly(I).poly(c12,U); Poly I-C; Celecoxib

Study Results

Participant Flow

Recruitment Details	9 Patients were enrolled in Phase I. 6 Patients were enrolled in Phase II prior to study termination (funding).

Arm/Group Title	Surgery Only	Chemokin Modulatory Regimen (5 MU/m2)	Chemokin Modulatory Regimen (10 MU/m2)	Chemokin Modulatory Regimen (20 MU/m2)
Arm/Group Description	Surgical resection only, performed as standard of care for the disease	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days
Period Title: Overall Study
STARTED	2	3	3	7
COMPLETED	2	3	3	7
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Surgery Only	Chemokine Modulatory Regimen (5 MU/m2)	Chemokine Modulatory Regimen (10 MU/m2)	Chemokine Modulatory Regimen (20 MU/m2)	Total
Arm/Group Description	Surgical resection only, performed as standard of care for the disease	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.	Total of all reporting groups
Overall Participants	2	3	3	7	15
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 50%	1 33.3%	1 33.3%	6 85.7%	9 60%
>=65 years	1 50%	2 66.7%	2 66.7%	1 14.3%	6 40%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (4.2)	62.7 (13.7)	60.0 (15.9)	47.1 (15.3)	55.1 (15.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 66.7%	0 0%	4 57.1%	6 40%
Male	2 100%	1 33.3%	3 100%	3 42.9%	9 60%
Region of Enrollment (participants) [Number]
United States	2 100%	3 100%	3 100%	7 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Change in the Number of Tumor-infiltrating CD8+ Cells.
Description	This will be assessed by the increase in the total number of tumor-infiltrating CD8+ T cells in the resected, recurrent CRC lesions (measured as the ratio between the CD8 mRNA message and the expression of the housekeeping gene HPRT), comparing Arm A and Arm B.
Time Frame	Day of surgery: day 8-10

Outcome Measure Data

Analysis Population Description

The study was terminated prior to completion of enrollment for Phase II and the T-cell analysis was not completed.

Arm/Group Title	Surgery Only	Chemokin Modulatory Regimen Prior to Surgery (20 MU/m2)
Arm/Group Description	Surgical resection only, performed as standard of care for the disease	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 2 dose of and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.
Measure Participants	0	0

2. Secondary Outcome

Title	Treatment Related Adverse Events
Description	The number of adverse events experienced within 1 week of treatment. This was completed for the Phase II portion of the study.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

The study was terminated prior to completion of enrollment for Phase II. The Phase II portion of the study involved Surgery alone and Chemokin Modulatory Regimen prior to surgery at 20 MU/m2.

Arm/Group Title	Surgery Only	Chemokin Modulatory Regimen Prior to Surgery (20 MU/m2)
Arm/Group Description	Surgical resection only, performed as standard of care for the disease	Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 2 dose of 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.
Measure Participants	2	4
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	The adverse events were measured for 30 days after treatment.
Adverse Event Reporting Description	Definitions are as described in clinicaltrials.gov
Arm/Group Title	Surgery Only		Chemokin Modulatory Regimen Prior to Surgery (5 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (10 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (20 MU/m2)
Arm/Group Description	Surgical resection only, performed as standard of care for the disease		Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.		Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.		Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5, 10, and 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Chemokine modulatory regimen: Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.
All Cause Mortality
	Surgery Only		Chemokin Modulatory Regimen Prior to Surgery (5 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (10 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (20 MU/m2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)		0/3 (0%)		0/7 (0%)
Serious Adverse Events
	Surgery Only		Chemokin Modulatory Regimen Prior to Surgery (5 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (10 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (20 MU/m2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)		1/3 (33.3%)		1/7 (14.3%)
Investigations
Neutrophil count decreased	0/2 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Surgery Only		Chemokin Modulatory Regimen Prior to Surgery (5 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (10 MU/m2)		Chemokin Modulatory Regimen Prior to Surgery (20 MU/m2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		3/3 (100%)		3/3 (100%)		6/7 (85.7%)
Blood and lymphatic system disorders
Anemia	0/2 (0%)	0	3/3 (100%)	6	1/3 (33.3%)	1	2/7 (28.6%)	2
Cardiac disorders
Sinus tachycardia	0/2 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2	0/7 (0%)	0
Gastrointestinal disorders
Gastroesophageal reflux disease	0/2 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0
Nausea	0/2 (0%)	0	3/3 (100%)	3	1/3 (33.3%)	1	3/7 (42.9%)	3
Vomiting	0/2 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	2/7 (28.6%)	2
General disorders
Chills	0/2 (0%)	0	3/3 (100%)	4	3/3 (100%)	3	3/7 (42.9%)	3
Fatigue	0/2 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2	4/7 (57.1%)	4
Fever	0/2 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	2/7 (28.6%)	2
Flu like symptoms	0/2 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0
Pain	0/2 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/7 (14.3%)	1
Investigations
Aspartate aminotransferase increased	0/2 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/7 (28.6%)	2
Lymphocyte count decreased	0/2 (0%)	0	3/3 (100%)	3	0/3 (0%)	0	0/7 (0%)	0
Neutrophil count decreased	0/2 (0%)	0	1/3 (33.3%)	1	3/3 (100%)	4	3/7 (42.9%)	3
Platelet count decreased	0/2 (0%)	0	3/3 (100%)	3	1/3 (33.3%)	1	1/7 (14.3%)	1
Serum amylase increased	0/2 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	1/7 (14.3%)	1
White blood cell decreased	0/2 (0%)	0	2/3 (66.7%)	2	3/3 (100%)	4	2/7 (28.6%)	2
Metabolism and nutrition disorders
Anorexia	0/2 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0	0/7 (0%)	0
Dehydration	0/2 (0%)	0	2/3 (66.7%)	2	2/3 (66.7%)	2	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/2 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1
Myalgia	0/2 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/7 (14.3%)	1
Nervous system disorders
Headache	0/2 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1
Vascular disorders
Flushing	0/2 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0
Hypertension	0/2 (0%)	0	2/3 (66.7%)	2	2/3 (66.7%)	3	0/7 (0%)	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.