Phase I/II Calcitriol in Lung Cancer

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00794547
• Collaborator: (none)
• Enrollment: 34
• Locations: 4
• Arms: 2
• Duration (Months): 56
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

According to the Cancer Atlas, lung cancer remains the major cancer among the 10.9 million new cases of cancer diagnosed annually worldwide. The mortality from lung cancer is greater than the combined mortality for breast, colon and prostate cancer combined. Most patients with metastatic non-small-cell lung cancer (NSCLC) are treated with platinum-based chemotherapy regimens. The drug combination of cisplatin and docetaxel is one of the commonly used regimens in metastatic NSCLC. Although both drugs are powerful disruptors of cell growth, positive therapeutic response rates to this therapy remain low for NSCLC patients, from 25% to 30%. While adding new biologics such as bevacizumab to the current treatment standard can improve treatment response, median survival for advanced NSCLC patients receiving this type of treatment remains low at under 12 months. Research studies have demonstrated that Vitamin D, and it's signaling pathways are important biological targets in cancer therapeutics. In vitro and in vivo calcitriol (1, 25 dihydroxycholecalciferol) is antiproliferative and potentiates the antitumor effects of cytotoxic agents (e.g. taxanes, platinum analogues). We have shown that administration of high doses of calcitriol and cisplatin is feasible and associated with complete tumor regressions in dogs with spontaneous cancers. Calcitriol has also shown to be synergistic with docetaxel both in preclinical as well as in a recent phase II clinical trial in prostate cancer. Based on these results and other supporting data from studies indicating that calcitriol functions as a potent and well tolerated anti-tumor agent when used in combination with drugs likes cisplatin and docetaxel, we hypothesize that introducing calcitriol into treatment regimes for NSCLC patients has the potential to demonstrably improve treatment response for these patients. The overall goals for conducting this phase I/II clinical study will be (1) to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of calcitriol in combination with cisplatin/docetaxel in patients with advanced NSCLC, (2) to assess the response rates of patients with advanced NSCLC to the combination of calcitriol with cisplatin/docetaxel, (3) to evaluate the pharmacokinetics (PK) of administering calcitriol intravenously at the MTD, and (4) to evaluate correlations between calcitriol PK and changes on specific coding regions of the gene associated with calcitriol breakdown.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Calcitriol; Drug: Calcitriol	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Clinical Trial of Intravenous (IV) Calcitriol With Fixed Dose of Cisplatin and Docetaxel in Advanced Non-Small Cell Lung Cancer
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 In the Phase I part of the study, we will test the safety of calcitriol along with standard chemotherapy. In addition, the goal is to see what effects (good and bad) it has on you and your type of Non-Small Cell Lung Cancer. This study is ongoing. In this portion of the study, we are testing increasing doses of calcitriol in combination with standard chemotherapy. If 2/3 patients at any dose level experience side effects that are limiting, we will call the dose level below that dose the maximum tolerated dose.	Drug: Calcitriol; Escalating dose of Calcitriol will be infused IV over 1 hour every 21 days.
Experimental: 2 In the Phase II part of the study, we will find out the response of subjects' cancer has to the combination of a fixed dose of calcitriol (determined in the phase I study) with standard chemotherapy.	Drug: Calcitriol; In this portion of the study, all patients will get the same dose of calcitriol (determined from the Phase I study) along with the standard chemotherapy

Outcome Measures

Primary Outcome Measures

1. MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) [5 years]

   The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.

2. Number of Participants That Experience Grade 3 or Greater Neutropenia [30 days after last dose]

   The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. Toxicity was assessed, in part, by noting the number of participants that experience grade 3 or greater neutropenia in each phase of the trial. Toxicities were recorded using NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 and were followed for 30 days after the date of withdrawal from study drug.

3. Median Time to Progression [5 years]

   The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, median time to progression was determined. Progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

4. Median Overall Survival [5 years]

   The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, overall survival was determined.

Secondary Outcome Measures

1. Mean AUC 1,25-D3 Concentration at 12 and 24 Hours [12 and 24 hours post dose]

   The mean AUC (area under the curve) concentrations of 1,25-D3 from 0-12 hours and 0-24 hours will be calculated.

Other Outcome Measures

1. To Correlate the Pharmacokinetic Parameters of Systemic Calcitriol Exposure (AUC) With SNPs of the 24-hydroxylase (CYP24), the Major Vitamin D3 Inactivating Enzyme. [3-6 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Proven histological or cytological diagnosis of stage IIIB (malignant pleural effusion) IV NSCLC.

2. Age more than 18 years

3. Performance status must be ECOG 0-1.

4. No prior or concurrent malignancy, except non-melanoma skin cancer, or CIS of the cervix, unless documented disease-free for more than 2 years.

5. No prior use of chemotherapy for stage IV NSCLC; Adjuvant therapy is permitted.

6. Adequate bone marrow, hepatic, and renal function, as evidenced by the following: WBC 3.0 x 109/L, neutrophils 1.5 x 109 /L; platelet count 100 x 109/L; Hgb> 10 g/dL (may be transfused to 10g/dL); total bilirubin within the upper limit of the institutional normal range; (transaminases SGOT or SGPT) 1.5 times the upper limit of the institutional normal range. Creatinine within the upper limit of the institutional normal range; creatinine clearance >50 ml/min

7. Patients must have measurable or evaluable disease (not required for the phase I part of the study)

8. Normal cardiac function with no history of uncontrolled heart disease

9. Female patients must not be pregnant; they must be post-menopausal or practicing an accepted form of birth control. If pregnancy is a possibility, a pregnancy test will be required prior to initiation of therapy.

10. Life expectancy of at least 12 weeks.

11. Patient and investigator signed study-specific consent form, indicating the investigational nature of the study

12. Patients must be accessible for treatment and follow-up.

13. No chemotherapy or radiotherapy within 3 weeks of study entry defined here as day 1 of therapy with calcitriol plus chemotherapy (6 weeks for mitomycin C or a nitrosourea).

14. No treatment with investigational drugs within 3 weeks of study entry.

15. No other serious illness or medical condition including unstable cardiac disease requiring treatment, new onset crescendo or rest angina; history of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures; or active infection are permitted. No evidence of grade > 2 peripheral neuropathy. No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80

16. Palliative radiation is permitted (as long as marrow exposed not greater than 10%; please see Appendix IV for reference) At least 1 week since the last palliative XRT.

17. Treated brain metastasis allowed with no waiting period following gamma knife and at least 2 weeks after whole brain XRT as long as neurologically stable.

Exclusion Criteria:

1. Known hypersensitivity to Vitamin D, docetaxel, cisplatin

2. Hypercalcemia (patients with serum albumin corrected calcium* > 10.7 mg/dL)

3. History of renal/bladder stones over the past 10 years

4. History of nephrectomy.

5. Uncontrolled heart disease, unstable angina, heart failure, current digoxin therapy

6. Thiazide, Digoxin or glucocorticoid therapy (except the pre-medication Dexamethasone used in the study as prescribed)

7. Unwillingness to stop calcium supplementation

8. Concurrent use of Phenytoin, Barbiturates, Rifampin, Carbamazepine, Phenobarbital or St John's wort.

9. Treatment with any investigational drug within 3 weeks before Day 1 of protocol

10. Any unresolved toxicity (NCI CTCAE version 3.0,>2) (Please see appendix V for link)

11. Pregnancy/Lactation

12. Patients with IIIB NSCLC who are eligible for definitive chemoradiation.

• Ca corrected = Ca (measured) + (0.8 x (4 - albumin))

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Ann Arbor Healthcare System	Ann Arbor	Michigan	United States	48105
2	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
3	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
4	Roswell Park Cancer Institute	Buffalo	New York	United States	14263

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Nithya Ramnath, MD, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00794547
• Other Study ID Numbers: UMCC 2008.042; HUM 21242; NCT00470431
• First Posted: Nov 20, 2008
• Last Update Posted: Dec 12, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by University of Michigan Rogel Cancer Center: lung cancer; nsclc
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Calcitriol

Study Results

Participant Flow

Arm/Group Title	Phase 1	Phase 2
Arm/Group Description	In the Phase I part of the study, we will test the safety of calcitriol along with standard chemotherapy. In addition, the goal is to see what effects (good and bad) it has on you and your type of Non-Small Cell Lung Cancer. This study is ongoing. In this portion of the study, we are testing increasing doses of calcitriol in combination with standard chemotherapy. If 2/3 patients at any dose level experience side effects that are limiting, we will call the dose level below that dose the maximum tolerated dose. Calcitriol: Escalating dose of Calcitriol will be infused IV over 1 hour every 21 days.	In the Phase II part of the study, we will find out the response of subjects' cancer has to the combination of a fixed dose of calcitriol (determined in the phase I study) with standard chemotherapy. Calcitriol: In this portion of the study, all patients will get the same dose of calcitriol (determined from the Phase I study) along with the standard chemotherapy
Period Title: Overall Study
STARTED	18	16
COMPLETED	18	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Overall Participants	34
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	22 64.7%
Male	12 35.3%
Region of Enrollment (participants) [Number]
United States	34 100%
Histology (participants) [Number]
Adenocarcinoma	21 61.8%
Squamous carcinoma	12 35.3%
NSCLC NOS	1 2.9%
Performance Status (participants) [Number]
Performance Status 0	16 47.1%
Performance Status 1	18 52.9%
Smoking Status (participants) [Number]
Never Smoker	2 5.9%
Ever Smoker	29 85.3%
Unknown	3 8.8%

Outcome Measures

1. Primary Outcome

Title	MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Description	The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Eighteen patients were enrolled, and 16 were evaluable for toxicity assessments. Two patients were not evaluable as they progressed prior to completion of cycle 1.

Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Measure Participants	16
Number [mcg/m^2]	60

2. Primary Outcome

Title	Number of Participants That Experience Grade 3 or Greater Neutropenia
Description	The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. Toxicity was assessed, in part, by noting the number of participants that experience grade 3 or greater neutropenia in each phase of the trial. Toxicities were recorded using NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 and were followed for 30 days after the date of withdrawal from study drug.
Time Frame	30 days after last dose

Outcome Measure Data

Analysis Population Description

Thirty-four patients were enrolled (18 in phase I and 16 in phase II). 16 of 18 patients enrolled in the Phase 1 portion of the study were evaluable for toxicity. One patient in the phase II study went to another therapy prior to the 30 day window for a confirmatory scan and was thus excluded from analysis.

Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Measure Participants	31
# of Phase 1 Participants w/ Grade 3+ Neutropenia	8 23.5%
# of Phase 2 Participants w/ Grade 3+ Neutropenia	9 26.5%

3. Primary Outcome

Title	Median Time to Progression
Description	The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, median time to progression was determined. Progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

22 patients were treated at the Maximum Tolerated Dose, including 6 phase I patients who received the MTD during the phase 1 component. 1 of 6 phase 1 patients was not evaluable due to toxicity. 1 patient (of 16) in the phase 2 study went to another therapy prior to the 30 day window and was excluded from analysis. 20 patients were analyzed.

Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Measure Participants	20
Median (95% Confidence Interval) [months]	5.8

4. Primary Outcome

Title	Median Overall Survival
Description	The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, overall survival was determined.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

22 patients were treated at the Maximum Tolerated Dose, including 6 phase I patients who received the MTD during the phase 1 component. 1 of 6 phase 1 patients was not evaluable due to toxicity. 1 patient (of 16) in the phase 2 study went to another therapy prior to the 30 day window and was excluded from analysis. 20 patients were analyzed.

Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Measure Participants	20
Median (95% Confidence Interval) [months]	8.7

5. Secondary Outcome

Title	Mean AUC 1,25-D3 Concentration at 12 and 24 Hours
Description	The mean AUC (area under the curve) concentrations of 1,25-D3 from 0-12 hours and 0-24 hours will be calculated.
Time Frame	12 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

Patients from the phase II portion of the study were included in the pharmacokinetics analysis

Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
Measure Participants	16
AUC 0-12 Hours	15.95 (0.92)
AUC 0-24 Hours	31.74 (1.92)

6. Other Pre-specified Outcome

Title	To Correlate the Pharmacokinetic Parameters of Systemic Calcitriol Exposure (AUC) With SNPs of the 24-hydroxylase (CYP24), the Major Vitamin D3 Inactivating Enzyme.
Time Frame	3-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Arm/Group Title	Calcitriol + Cisplatin + Docetaxel
Arm/Group Description	Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m^2 (every 21 days), along with Cisplatin, 75 mg/m^2 (every three weeks), and Docetaxel, 75 mg/m^2 (every three weeks).
All Cause Mortality
	Calcitriol + Cisplatin + Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Calcitriol + Cisplatin + Docetaxel
	Affected / at Risk (%)	# Events
Total	20/34 (58.8%)
Blood and lymphatic system disorders
Low Neutrophils/granulocytes (ANC/AGC)	2/34 (5.9%)	2
Cardiac disorders
Supraventricular and nodal arrhythmia	2/34 (5.9%)	2
Hypotension	2/34 (5.9%)	2
Pain-Chest	1/34 (2.9%)	1
Gastrointestinal disorders
Abdominal Pain	1/34 (2.9%)	1
Colitis	1/34 (2.9%)	1
Dehydration	3/34 (8.8%)	3
Diarrhea	3/34 (8.8%)	3
Esophagitis	1/34 (2.9%)	1
Nausea	2/34 (5.9%)	2
Vomiting	2/34 (5.9%)	2
Infections and infestations
Febrile neutropenia	3/34 (8.8%)	3
Lung Infection	2/34 (5.9%)	2
Upper Airway Infection	1/34 (2.9%)	1
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)	1/34 (2.9%)	1
Glomerular filtration rate	1/34 (2.9%)	1
Glucose, serum-low (hypoglycemia)	1/34 (2.9%)	1
Phosphate, serum-low (hypophosphatemia)	1/34 (2.9%)	1
Sodium, serum-low (hyponatremia)	1/34 (2.9%)	1
Musculoskeletal and connective tissue disorders
Pain-Back	1/34 (2.9%)	1
Nervous system disorders
Syncope (fainting)	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory	1/34 (2.9%)	1
Dyspnea (shortness of breath)	1/34 (2.9%)	1
Vascular disorders
Thrombosis/thrombus/embolism	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Calcitriol + Cisplatin + Docetaxel
	Affected / at Risk (%)	# Events
Total	34/34 (100%)
Blood and lymphatic system disorders
Low Hemoglobin	14/34 (41.2%)	23
Low Leukocytes (total WBC)	14/34 (41.2%)	24
Lymphopenia	11/34 (32.4%)	24
Low Neutrophils/granulocytes (ANC/AGC)	14/34 (41.2%)	23
Low Platelets	8/34 (23.5%)	15
Cardiac disorders
Atrial fibrillation	3/34 (8.8%)	5
Sinus tachycardia	4/34 (11.8%)	6
Hypertension	3/34 (8.8%)	3
Hypotension	7/34 (20.6%)	10
Chest Pain	3/34 (8.8%)	4
Ear and labyrinth disorders
Tinnitus	4/34 (11.8%)	5
Eye disorders
Vision-blurred vision	3/34 (8.8%)	3
Gastrointestinal disorders
Anorexia	15/34 (44.1%)	17
Constipation	7/34 (20.6%)	7
Dehydration	6/34 (17.6%)	10
Diarrhea	10/34 (29.4%)	15
Dysphagia (difficulty swallowing)	3/34 (8.8%)	4
Mucositis/stomatitis	7/34 (20.6%)	7
Nausea	21/34 (61.8%)	29
Taste alteration (dysgeusia)	9/34 (26.5%)	13
Vomiting	12/34 (35.3%)	16
Abdominal Pain	6/34 (17.6%)	10
Throat Pain	5/34 (14.7%)	5
General disorders
Fatigue	17/34 (50%)	28
Fever	3/34 (8.8%)	3
Rigors/chills	4/34 (11.8%)	4
Edema: limb	4/34 (11.8%)	7
Pain NOS	3/34 (8.8%)	3
Infections and infestations
Febrile neutropenia	4/34 (11.8%)	4
Investigations
Weight loss	4/34 (11.8%)	7
Metabolism and nutrition disorders
Elevated ALT, SGPT (serum glutamic pyruvic transaminase)	5/34 (14.7%)	15
Elevated AST, SGOT(serum glutamic oxaloacetic transaminase)	9/34 (26.5%)	13
Albumin, serum-low (hypoalbuminemia)	11/34 (32.4%)	15
Elevated Alkaline phosphatase	7/34 (20.6%)	12
Bilirubin (hyperbilirubinemia)	4/34 (11.8%)	5
Calcium, serum-low (hypocalcemia)	7/34 (20.6%)	11
Elevated Creatinine	4/34 (11.8%)	6
Glucose, serum-high (hyperglycemia)	17/34 (50%)	42
Phosphate, serum-low (hypophosphatemia)	4/34 (11.8%)	6
Potassium, serum-high (hyperkalemia)	6/34 (17.6%)	6
Potassium, serum-low (hypokalemia)	6/34 (17.6%)	8
Sodium, serum-low (hyponatremia)	14/34 (41.2%)	20
Musculoskeletal and connective tissue disorders
Muscle weakness	5/34 (14.7%)	6
Back Pain	7/34 (20.6%)	10
Bone Pain	3/34 (8.8%)	3
Limb Pain	3/34 (8.8%)	4
Nervous system disorders
Dizziness	7/34 (20.6%)	8
Neuropathy: sensory	4/34 (11.8%)	5
Head Pain	5/34 (14.7%)	6
Psychiatric disorders
Insomnia	3/34 (8.8%)	5
Renal and urinary disorders
Urinary retention	3/34 (8.8%)	3
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/34 (11.8%)	5
Bronchospasm, wheezing	3/34 (8.8%)	3
Cough	9/34 (26.5%)	11
Dyspnea	8/34 (23.5%)	14
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	5/34 (14.7%)	5
Rash/desquamation	7/34 (20.6%)	7

Limitations/Caveats

[Not Specified]

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.