Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03007979
• Collaborator: Pfizer (Industry)
• Enrollment: 55
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 66.5
• Patients Per Site: 27.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The investigators propose to conduct a study to test an alternative dosing schedule of palbociclib. With the current three-week on and one week off schedule, a significant number of patients develop grade 3 or higher degree of neutropenia and require dose reduction and sometimes discontinuation. This potentially compromises the efficacy of the drug. In addition, as the half-life of palbociclib is 27 hours, 1 week break with the standard 3 weeks on and 1 week off dosing schedule could potentially lead to recovery of Rb phosphorylation during the off week. Hence, the investigators propose a 5 days on and 2 days off schedule each week without any weeks off drug. Although the cumulative doses each 28-day cycle is roughly the same with this schedule compared to conventional dosing, the bone marrow is not exposed to the drug continuously for 21 days and rather gets frequent breaks from therapy. The investigators hypothesize that the 5 days on and 2 days off schedule is more tolerable with less frequent high grade neutropenia and dose interruption/reduction. In addition, this schedule also provides for a more continuous drug delivery to the patient since there is not a week's break in therapy, which could ultimately prove to be more efficacious.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Breast Carcinoma; Cancer of Breast; Malignant Tumor of Breast	Drug: Palbociclib; Drug: Letrozole; Drug: Fulvestrant; Procedure: Optional research biopsy; Drug: Goserelin; Procedure: Research blood draw; Procedure: Circulating tumor cell blood draw; Procedure: Tumor biopsy (optional)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer
• Actual Study Start Date: Jun 15, 2017
• Actual Primary Completion Date: Mar 13, 2020
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Palbociclib + letrozole or + fulvestrant Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. Optional research biopsy at baseline and progression Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression

Drug: Palbociclib; Palbociclib at a dose of 125 mg should be taken by mouth with food on a 5 days on/2 days off schedule; Other Names: Ibrance ; Drug: Letrozole; Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle, at a dose of 2.5 mg.; Other Names: Femara ; Drug: Fulvestrant; Patients who are receiving fulvestrant will receive it at a dose of 500 mg as two 5 mL intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter.; Other Names: Faslodex ; Procedure: Optional research biopsy; Patients may consent to paired tumor biopsies at baseline and time of progression.; Drug: Goserelin; Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- and peri-menopausal women only.; Other Names: Zoladex ; Procedure: Research blood draw; -Blood will be drawn at the following time points for serum, plasma, cfDNA, and germline DNA (only at baseline): Baseline C1D15 C2D1 Every 2-3 months thereafter (to coincide with imaging studies) Time of progression; Procedure: Circulating tumor cell blood draw; -Baseline, cycle 2 day 1, post 2 or 3 months of therapy (to coincide with first tumor imaging), and progression; Procedure: Tumor biopsy (optional); -Baseline and progression

Outcome Measures

Primary Outcome Measures

1. Rate of Grade 3 or Higher Neutropenia [Through the first 29 days of treatment]

   The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. Grade 3 neutropenia: <1000-500/mm^3; <1.0-0.5 x 10e9/L Grade 4 neutropenia: <500/mm^3; <0.5 x 10e9/L

Secondary Outcome Measures

1. Rate of Grade 3 or Higher Neutropenia [Through 30 day follow-up (estimated to be 25 months)]

   The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. Grade 3 neutropenia: <1000-500/mm^3; <1.0-0.5 x 10e9/L Grade 4 neutropenia: <500/mm^3; <0.5 x 10e9/L

2. Rate of Palbociclib Dose Reduction [Through the completion of treatment (estimated to be 24 months)]

   -Percentage of participants who have a palbociclib dose reduction during treatment

3. Rate of Palbociclib Dose Interruption [Through the completion of treatment (estimated to be 24 months)]

   -Percentage of participants who have a palbociclib dose interruption during treatment

4. Rate of Palbociclib Discontinuation [Through the completion of treatment (estimated to be 24 months)]

   -Percentage of participants who discontinue palbociclib

5. Adverse Event Profile of Palbociclib [Through the 30 day follow-up (estimated to be 25 months)]

   -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

6. Progression-free Survival (PFS) [1 year]

   PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

7. Overall Response Rate (Complete Response + Partial Response) [Time of progression (estimated to be 24 months)]

   Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

8. Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months) [Time of progression (estimated to be 24 months)]

   Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed metastatic ER+ and/or PR+ and HER2- breast cancer who are candidates for palbociclib in combination with either letrozole or fulvestrant per treating physician.

• Presence of measurable or non-measurable disease by RECIST 1.1 criteria.

• One prior systemic therapy in the metastatic setting is allowed, but patients who have not had any prior systemic therapies in the metastatic setting are also eligible.

*Note: patients who were started on endocrine therapy monotherapy as their 1st line or 2nd line systemic therapy in the metastatic setting for no more than 28 days and without clinical progression prior to the initiation of the study drug therapy are allowed to enroll on the study as their 1st line or 2nd line therapy, respectively.

• At least 18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Normal bone marrow and organ function as defined below:

• Absolute neutrophil count ≥ 1,500/mcl

• Platelets ≥ 100,000/mcl

• Total bilirubin ≤ institutional upper limit of normal (IULN) or total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with documented Gilbert's syndrome

• AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN (up to 5 x IULN in patients with liver disease)

• Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional normal (calculated by Creatinine Clearance Estimate by Cockcroft-Gault Equation)

• Pre- or post-menopausal women are allowed. If pre- or peri-menopausal, concurrent ovarian suppression for pre- or peri-menopausal women is required.

• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Able to swallow and retain oral medication.

• Washout of at least 3 weeks from prior chemotherapy or targeted therapy that induces myelosuppression and recovery of treatment related adverse events to grade 1 or less, with the exception of alopecia, is required prior to the start of palbociclib.

• Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Prior therapy with any CDK inhibitor.

• Currently receiving any other investigational agents.

• Currently receiving exogenous estrogen replacement (topical vaginal estrogen therapy is allowed).

• Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis which could affect the evaluation of all-cycle adverse events.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in the study.

• Receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days prior to registration.

• Clinically significant history of liver disease.

• A condition that would interfere with enteric absorption.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.

• Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with palbociclib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
2	University of Nebraska	Lincoln	Nebraska	United States	68588

Sponsors and Collaborators

• Washington University School of Medicine
• Pfizer

Investigators

• Principal Investigator: Cynthia X Ma, M.D., Ph.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 12, 2019

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03007979
• Other Study ID Numbers: 201612098
• First Posted: Jan 2, 2017
• Last Update Posted: Jul 22, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Breast Neoplasms; Neoplasms; Letrozole; Fulvestrant; Palbociclib; Goserelin

Study Results

Participant Flow

Arm/Group Title	Palbociclib + Letrozole or + Fulvestrant
Arm/Group Description	Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. Optional research biopsy at baseline and progression Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression
Period Title: Overall Study
STARTED	55
COMPLETED	54
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Palbociclib + Letrozole or + Fulvestrant
Arm/Group Description	Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. Optional research biopsy at baseline and progression Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression
Overall Participants	55
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	55 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	55 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 18.2%
White	45 81.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	55 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Grade 3 or Higher Neutropenia
Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. Grade 3 neutropenia: <1000-500/mm^3; <1.0-0.5 x 10e9/L Grade 4 neutropenia: <500/mm^3; <0.5 x 10e9/L
Time Frame	Through the first 29 days of treatment

Outcome Measure Data

Analysis Population Description

The following participants were not evaluable for this outcome measure: 4 participants did not take palbociclib dose as per protocol and were without dose-limiting toxicity; 2 participants withdrew in cycle 1, and 1 participant went off treatment in cycle 1 due to adverse events unrelated to the study.

Arm/Group Title	Palbociclib + Letrozole or + Fulvestrant
Arm/Group Description	Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. Optional research biopsy at baseline and progression Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression
Measure Participants	47
Count of Participants [Participants]	10 18.2%

2. Secondary Outcome

Title	Rate of Grade 3 or Higher Neutropenia
Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. Grade 3 neutropenia: <1000-500/mm^3; <1.0-0.5 x 10e9/L Grade 4 neutropenia: <500/mm^3; <0.5 x 10e9/L
Time Frame	Through 30 day follow-up (estimated to be 25 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Rate of Palbociclib Dose Reduction
Description	-Percentage of participants who have a palbociclib dose reduction during treatment
Time Frame	Through the completion of treatment (estimated to be 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Rate of Palbociclib Dose Interruption
Description	-Percentage of participants who have a palbociclib dose interruption during treatment
Time Frame	Through the completion of treatment (estimated to be 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Rate of Palbociclib Discontinuation
Description	-Percentage of participants who discontinue palbociclib
Time Frame	Through the completion of treatment (estimated to be 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Adverse Event Profile of Palbociclib
Description	-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Time Frame	Through the 30 day follow-up (estimated to be 25 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Overall Response Rate (Complete Response + Partial Response)
Description	Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
Time Frame	Time of progression (estimated to be 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months)
Description	Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame	Time of progression (estimated to be 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected from start of treatment through 30 days following completion of treatment.
Arm/Group Title	Palbociclib + Letrozole or + Fulvestrant
Arm/Group Description	Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. Optional research biopsy at baseline and progression Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression
All Cause Mortality
	Palbociclib + Letrozole or + Fulvestrant
	Affected / at Risk (%)	# Events
Total	3/54 (5.6%)
Serious Adverse Events
	Palbociclib + Letrozole or + Fulvestrant
	Affected / at Risk (%)	# Events
Total	11/54 (20.4%)
Cardiac disorders
Asystole	1/54 (1.9%)
Gastrointestinal disorders
Constipation	1/54 (1.9%)
Nausea	1/54 (1.9%)
Vomiting	2/54 (3.7%)
General disorders
Fever	1/54 (1.9%)
Generalized weakness	1/54 (1.9%)
Pain	3/54 (5.6%)
Infections and infestations
Sepsis	1/54 (1.9%)
Urinary tract infection	2/54 (3.7%)
Metabolism and nutrition disorders
Failure to thrive	1/54 (1.9%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/54 (1.9%)
Nervous system disorders
Intracranial hemorrhage	1/54 (1.9%)
Renal and urinary disorders
Acute kidney injury	1/54 (1.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/54 (1.9%)
Vascular disorders
Cellulitis	1/54 (1.9%)
Hypotension	1/54 (1.9%)
Superficial thrombophlebitis	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	Palbociclib + Letrozole or + Fulvestrant
	Affected / at Risk (%)	# Events
Total	54/54 (100%)
Blood and lymphatic system disorders
Anemia	41/54 (75.9%)
Gout	1/54 (1.9%)
Cardiac disorders
Chest pain - cardiac	2/54 (3.7%)
Heart failure	1/54 (1.9%)
Mitral valve disease	1/54 (1.9%)
Ear and labyrinth disorders
Tinnitus	1/54 (1.9%)
Vertigo	3/54 (5.6%)
Vestibular schwannoma	1/54 (1.9%)
Endocrine disorders
Hypothyroidism	2/54 (3.7%)
Eye disorders
Blurred vision	3/54 (5.6%)
Cataract	1/54 (1.9%)
Dry eye	2/54 (3.7%)
Eye lid pain/soreness	1/54 (1.9%)
Photophobia	1/54 (1.9%)
Red eye	3/54 (5.6%)
Watering eyes	2/54 (3.7%)
Gastrointestinal disorders
Abdominal pain	1/54 (1.9%)
Broken tooth	2/54 (3.7%)
C. difficile	1/54 (1.9%)
Constipation	17/54 (31.5%)
Diarrhea	28/54 (51.9%)
Dry lips	1/54 (1.9%)
Dry mouth	2/54 (3.7%)
Dyspepsia	13/54 (24.1%)
Dysphagia	5/54 (9.3%)
Gastric ulcer	1/54 (1.9%)
Gastroesophageal reflux disease	5/54 (9.3%)
Gingival pain	1/54 (1.9%)
Gout	3/54 (5.6%)
Hematochezia	1/54 (1.9%)
Hemorrhoidal hemorrhage	1/54 (1.9%)
Hemorrhoids	1/54 (1.9%)
Mucositis oral	14/54 (25.9%)
Nausea	31/54 (57.4%)
Oral dysesthesia	1/54 (1.9%)
Oral pain	1/54 (1.9%)
Stomach pain	1/54 (1.9%)
Toothache	1/54 (1.9%)
Ulcerative colitis	1/54 (1.9%)
Vomiting	15/54 (27.8%)
General disorders
Body aches	3/54 (5.6%)
Breast pain	6/54 (11.1%)
Buttock pain	3/54 (5.6%)
Chills	12/54 (22.2%)
Cold sensitivity	1/54 (1.9%)
Common cold	4/54 (7.4%)
Dilation of appendix with periappendiceal fat stranding seen on CT	1/54 (1.9%)
Edema face	1/54 (1.9%)
Edema limbs	17/54 (31.5%)
Edema trunk	2/54 (3.7%)
Fatigue	45/54 (83.3%)
Fever	7/54 (13%)
Flu-like symptoms	2/54 (3.7%)
Gait disturbance	1/54 (1.9%)
Hyperhidrosis	1/54 (1.9%)
Itchy scalp	1/54 (1.9%)
Mole pain	1/54 (1.9%)
Non-cardiac chest pain	3/54 (5.6%)
Pain	19/54 (35.2%)
Peeling lips	1/54 (1.9%)
Right arm numbness	2/54 (3.7%)
Right thumb bump	2/54 (3.7%)
Sciatic pain	1/54 (1.9%)
Tick bite	2/54 (3.7%)
Immune system disorders
Allergic reaction	2/54 (3.7%)
Infections and infestations
Acute bronchitis	1/54 (1.9%)
Bronchitis	3/54 (5.6%)
COVID-19	1/54 (1.9%)
Extremity infection	2/54 (3.7%)
Lung infection	3/54 (5.6%)
Otitis media	1/54 (1.9%)
Paronychia - infection right middle	1/54 (1.9%)
Pharyngitis	1/54 (1.9%)
Respiratory syncytial virus (RSV)	3/54 (5.6%)
Sinusitis	10/54 (18.5%)
Skin infection	5/54 (9.3%)
Tooth infection	1/54 (1.9%)
Upper respiratory infection	8/54 (14.8%)
Urinary tract infection	6/54 (11.1%)
Yeast infection under right breast	1/54 (1.9%)
Injury, poisoning and procedural complications
Bruising	2/54 (3.7%)
Bug bite	2/54 (3.7%)
Burn - left hand	2/54 (3.7%)
Fall	9/54 (16.7%)
Fracture	1/54 (1.9%)
Head injury - upper left occipital swelling	1/54 (1.9%)
Left hand puncture wound	1/54 (1.9%)
Radiation recall reaction (dermatologic)	1/54 (1.9%)
Snake bite	1/54 (1.9%)
Spinal fracture	1/54 (1.9%)
Wrist fracture	1/54 (1.9%)
Investigations
Activated partial thromboplastin time prolonged	1/54 (1.9%)
Alanine aminotransferase increased	15/54 (27.8%)
Alkaline phosphatase increased	15/54 (27.8%)
Aspartate aminotransferase increased	16/54 (29.6%)
Creatinine increased	18/54 (33.3%)
Hemoglobin increased	2/54 (3.7%)
INR increased	1/54 (1.9%)
Lymphocyte count decreased	39/54 (72.2%)
Lymphocyte count increased	1/54 (1.9%)
Neutrophil count decreased	47/54 (87%)
Platelet count decreased	18/54 (33.3%)
Weight gain	1/54 (1.9%)
Weight loss	3/54 (5.6%)
White blood cell count decreased	49/54 (90.7%)
Metabolism and nutrition disorders
Anorexia	22/54 (40.7%)
Hypercalcemia	19/54 (35.2%)
Hyperglycemia	11/54 (20.4%)
Hyperkalemia	16/54 (29.6%)
Hypernatremia	5/54 (9.3%)
Hypoalbuminemia	8/54 (14.8%)
Hypocalcemia	15/54 (27.8%)
Hypoglycemia	2/54 (3.7%)
Hypokalemia	9/54 (16.7%)
Hypomagnesemia	1/54 (1.9%)
Hyponatremia	17/54 (31.5%)
Hypophosphatemia	4/54 (7.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	24/54 (44.4%)
Arthritis	6/54 (11.1%)
Back pain	29/54 (53.7%)
Bilateral leg pain	1/54 (1.9%)
Bone pain	6/54 (11.1%)
Chest wall pain	1/54 (1.9%)
Flank pain	1/54 (1.9%)
Generalized muscle weakness	2/54 (3.7%)
Hand cramps	1/54 (1.9%)
Hip pain	2/54 (3.7%)
Knee pain	5/54 (9.3%)
Left sided flank pain	1/54 (1.9%)
Leg stiffness	3/54 (5.6%)
Muscle cramp	2/54 (3.7%)
Muscle spasm	2/54 (3.7%)
Muscle weakness lower limb	1/54 (1.9%)
Myalgia	9/54 (16.7%)
Neck pain	4/54 (7.4%)
Osteonecrosis of jaw	1/54 (1.9%)
Osteopenia	3/54 (5.6%)
Pain in extremity	5/54 (9.3%)
Right arm pain	1/54 (1.9%)
Sacroliac joint pain	3/54 (5.6%)
Shoulder pain	3/54 (5.6%)
Sternum pain	1/54 (1.9%)
Nervous system disorders
Acoustic neuroma	1/54 (1.9%)
Dizziness	22/54 (40.7%)
Dysgeusia	11/54 (20.4%)
Facial nerve disorder	1/54 (1.9%)
Headache	24/54 (44.4%)
Paresthesia	1/54 (1.9%)
Peripheral motor neuropathy	2/54 (3.7%)
Peripheral sensory neuropathy	15/54 (27.8%)
Right arm numbness	1/54 (1.9%)
Sinus pain	2/54 (3.7%)
Spasticity	1/54 (1.9%)
Syncope	1/54 (1.9%)
Psychiatric disorders
ADHD	1/54 (1.9%)
Anxiety	14/54 (25.9%)
Confusion	1/54 (1.9%)
Depression	15/54 (27.8%)
Hallucinations	1/54 (1.9%)
Insomnia	21/54 (38.9%)
Mood swings	1/54 (1.9%)
Renal and urinary disorders
Urinary frequency	2/54 (3.7%)
Urinary retention	1/54 (1.9%)
Urine discoloration	1/54 (1.9%)
Reproductive system and breast disorders
Vaginal discharge	1/54 (1.9%)
Vaginal dryness	2/54 (3.7%)
Vaginal itch	1/54 (1.9%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	9/54 (16.7%)
Asthma	1/54 (1.9%)
Cough	23/54 (42.6%)
Dyspnea	17/54 (31.5%)
Epistaxis	6/54 (11.1%)
Hoarseness	1/54 (1.9%)
Laryngeal inflammation	1/54 (1.9%)
Nasal congestion	5/54 (9.3%)
Nasal drainage	1/54 (1.9%)
Nasal dryness	1/54 (1.9%)
Pleural effusion	5/54 (9.3%)
Postnasal drip	4/54 (7.4%)
Productive cough	1/54 (1.9%)
Rhinovirus	1/54 (1.9%)
Sleep apnea	2/54 (3.7%)
Sore throat	9/54 (16.7%)
Voice alteration	1/54 (1.9%)
Skin and subcutaneous tissue disorders
Alopecia	23/54 (42.6%)
Blister	3/54 (5.6%)
Brittle nail	2/54 (3.7%)
Dry skin	10/54 (18.5%)
Erythema multiforme	1/54 (1.9%)
Erythema right breast	1/54 (1.9%)
Eye lid pain	1/54 (1.9%)
Hyperhidrosis	7/54 (13%)
Itchy skin	4/54 (7.4%)
Nail loss	1/54 (1.9%)
Nodule	2/54 (3.7%)
Open cutaneous area left breast	1/54 (1.9%)
Oral fissure	1/54 (1.9%)
Peeling skin palms of hands	1/54 (1.9%)
Psoriasis	3/54 (5.6%)
Rash acneiform	3/54 (5.6%)
Rash maculopapular	12/54 (22.2%)
Skin bumps	1/54 (1.9%)
Skin hypopigmentation	1/54 (1.9%)
Sores bilateral nares	1/54 (1.9%)
Stomach rash	1/54 (1.9%)
Tender nail bed	1/54 (1.9%)
Vascular disorders
Hot flashes	28/54 (51.9%)
Hypertension	47/54 (87%)
Lymphedema	6/54 (11.1%)
Thromboembolic event	4/54 (7.4%)

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.