HELEX: Extension Study of Lapatinib Plus Herceptin With or Without Endocrine Therapy

• Sponsor: Baylor Breast Care Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00999804
• Collaborator: Translational Breast Cancer Research Consortium (Other), GlaxoSmithKline (Industry)
• Enrollment: 128
• Locations: 8
• Arms: 2
• Anticipated Duration (Months): 147
• Patients Per Site: 16
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Breast cancer is the most common malignancy in the U.S. Targeted therapies such as tamoxifen have been revolutionary in reducing tumor recurrences and mortality in early breast cancer. Using this successful paradigm, there has been a continued search for other targeted biologic therapies directed at receptors with known potential for promoting tumor growth.

The estrogen receptor (ER) and/or the HER signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. Molecular targets of these pathways provide the most effective therapies in appropriately selected patients. However, de novo and acquired resistance remain major obstacles to successful treatment, and understanding the molecular pathways responsible for this resistance would enable the discovery of new strategies to overcome it.

The superiority of multi-drug HER2-targeted therapy over single agent therapy has been demonstrated in the preclinical setting using mouse xenografts. Trastuzumab, pertuzumab, lapatinib, and gefitinib, represent a group of therapeutic agents that target the HER family by different molecular mechanisms. Used as single agents in the MCF7/HER2-18 xenograft model, these drugs restored or enhanced sensitivity to tamoxifen. However, tumor growth inhibition lasted only 2-3 months before resistance to treatments occurred. However, when gefitinib, a HER1 inhibitor, was added to the two-antibody (T+P) regimen to block signals from HER1 dimers, a complete disappearance of nearly all xenograft tumors was observed; moreover, there was evidence of complete tumor eradication in 50% of the mice. The combination of lapatinib + trastuzumab was also highly effective in eradication of tumor burden, with no evidence of re-growth after 200 days. These xenograft models demonstrate that multi-drug HER2-targeted therapy more effectively induces apoptosis and inhibits proliferation, thereby resulting in tumor regression. Furthermore, HER2 combination therapy appears to more effectively reduce levels of phosphorylated pAKT and MAPK, thus resulting in sustained tumor inhibition.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Lapatinib; Drug: Letrozole; Drug: Trastuzumab	Phase 2

Detailed Description

Breast cancer cells have certain characteristics or traits--these traits are called biomarkers. There are three biomarkers that help doctors decide which treatment to give any given patient. These biomarkers are the estrogen receptor (ER), progesterone receptor (PgR), and HER2 protein. Breast cancer cells that have a large number of estrogen or progesterone receptors are called ER and/or PgR positive. Cancers that are ER and/or PgR positive use the hormones estrogen and progesterone to help them grow. Not all breast cancers are ER or PgR positive. Patients are being asked to take part in this study that have a special type of breast cancer called HER2 positive breast cancer. HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor-2 (HER2). HER2 is located on the outer surface of a cancer cell. The HER2 protein sends a signal to the inside of the cancer cells telling it to grow and divide.

Two medications that directly target this HER2 protein. One is called trastuzumab(Herceptin), and the other is called lapatinib (Tykerb). Both medications are FDA-approved for the treatment of women with HER2+ breast cancer. Each medication attaches to the protein so that it can no longer function. Once the protein stops working, the cancer cells can no longer make copies of themselves. This makes cancer shrink. Both drugs target HER2; however each drug works a little bit differently.

Some patients respond better to Herceptin, and some patients respond better to Tykerb. Right now, we are not sure why some patients respond to one drug but do not respond to the other drug. One possibility is that in some patients, the HER2 protein finds another way to send its message to the inside of the cell (similar to a road detour). For example, when one path is "closed" because the drug is blocking it, the HER2 protein finds a different way to send its signal. We think that we can completely block the HER2 protein by giving patients both Tykerb and Herceptin.

Some patients with HER positive breast cancer are also ER and/or PgR positive. Even after HER2 is completely blocked, these types of cancer cells can still grow by using the estrogen or progesterone receptor. If a patient is told they are ER and/or PgR positive, they will also take an anti-estrogen pill along with Tykerb and Herceptin. We think that we can stop cancer growth more completely by blocking both the HER2 protein and the ER/PR receptors.

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TBCRC 023: A Randomized Multicenter Phase II Neoadjuvant Trial of Lapatinib Pus Trastuzumab, With or Without Endocrine Therapy for 12 Weeks vs. 24 Weeks in Patients With HER2 Overexpressing Breast Cancer
• Actual Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Nov 1, 2014
• Anticipated Study Completion Date: Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 24-week arm Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.	Drug: Lapatinib; 1000 mg of Lapatinib by mouth daily; Other Names: TyKerb ; Drug: Letrozole; Letrozole, 2.5 mg by mouth daily (for hormone receptor positive participants only); Other Names: Femara ; Drug: Trastuzumab; 6 mg/kg intravenously, every 3 weeks; Other Names: Herceptin
Active Comparator: 12-week arm Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy.	Drug: Lapatinib; 1000 mg of Lapatinib by mouth daily; Other Names: TyKerb ; Drug: Letrozole; Letrozole, 2.5 mg by mouth daily (for hormone receptor positive participants only); Other Names: Femara ; Drug: Trastuzumab; 6 mg/kg intravenously, every 3 weeks; Other Names: Herceptin

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response [12 or 24 week depending the arm assignment]

   Pathologic complete response was defined as no residual invasive cancer in the breast, after 12 or 24 weeks of lapatinib/trastuzumab with or without endocrine therapy. This outcome is based on patient's pathological report. We are not measuring the clinical response. Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [12 week or 24 weeks depending on arm assignment]

   the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy

2. Total Pathologic Complete Response [12 weeks or 24 weeks depending on arm assignment]

   pathologic complete response was defined as no residual invasive cancer in the breast and the axillary lymph nodes.

3. Clinical Response [12 weeks or 24 weeks depending on arm assignment]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. All patients must be female and at least 18 years of age.

2. Signed informed consent.

3. Locally advanced breast cancers are eligible. Locally advanced cancers must be of clinical and/or radiologic size >3 cm, or >2 cm with clinical evidence of axillary nodal involvement*. (If tumors are less than 3 cm, we will use the radiologically measured tumor size to determine if the tumor meets the minimal size requirements.)

4. Patients must have histologically confirmed invasive mammary carcinoma that is HER2 overexpressing, defined as 3+ by immunohistochemistry, or a FISH/CEP ratio greater than 2.

5. Negative serum pregnancy test (HCG) within 7 days of starting study drug, if of child-bearing potential.

6. Kidney and liver function tests - all within 1.5 times the institutional upper limit of normal.

7. Performance status (WHO/ECOG scale) 0-1 and life expectancy >6 months.

8. No evidence of brain or leptomeningeal disease, or any other Stage IV disease.

9. No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.

Exclusion Criteria:

1. Patients with bilateral breast cancer.

2. Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.

3. Severe underlying chronic illness or disease.

4. Cardiomyopathy or baseline LVEF less than 50%.

5. Other investigational drugs while on study.

6. Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.

7. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded

8. Taking any lapatinib prohibited medication(s)

9. Inability or unwillingness to comply with, or follow study procedures.

10. Patients who have received any form of treatment for breast cancer within the past five years, including surgical resection, chemotherapy, endocrine therapy, or biologic therapy.

11. Patients with a prior history of ipsilateral invasive breast cancer or carcinoma in situ who present with a new primary.

12. Patients with known active, infectious Hepatitis B, Hepatitis C, or HIV.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Birmingham	Birmingham	Alabama	United States	35294
2	University of Chicago	Chicago	Illinois	United States	60637
3	Indiana University	Indianapolis	Indiana	United States	46202
4	Johns Hopkins	Baltimore	Maryland	United States	21231
5	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02130
6	Duke University	Durham	North Carolina	United States	27705
7	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
8	Baylor College of Medicine Lester and Sue Smith Breast Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor Breast Care Center
• Translational Breast Cancer Research Consortium
• GlaxoSmithKline

Investigators

• Principal Investigator: Mothaffar Rimawi, MD, Baylor College of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mothaffar Rimawi, Professor, Baylor Breast Care Center
• ClinicalTrials.gov Identifier: NCT00999804
• Other Study ID Numbers: H-25846
• First Posted: Oct 22, 2009
• Last Update Posted: Jun 2, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mothaffar Rimawi, Professor, Baylor Breast Care Center: Locally Advanced Breast Cancer Neoadjuvant Endocrine
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Letrozole; Lapatinib

Study Results

Participant Flow

Recruitment Details	Participants were recruited between October 2011 and July 2014 at 10 study sites: Baylor College of Medicine, UAB, University of Chicago, Johns Hopkins, Duke, Indiana University, Vanderbilt, MDACC, DFCI, and Mayo Clinic.
Pre-assignment Detail	Participants screened up to 28-day period.

Arm/Group Title	24-week Arm	12-week Arm
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Period Title: Overall Study
STARTED	85	43
COMPLETED	64	38
NOT COMPLETED	21	5

Baseline Characteristics

Arm/Group Title	24-week Arm	12-week Arm	Total
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Total of all reporting groups
Overall Participants	85	43	128
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50	57	52
Sex: Female, Male (Count of Participants)
Female	85 100%	43 100%	128 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 17.6%	9 20.9%	24 18.8%
Not Hispanic or Latino	69 81.2%	33 76.7%	102 79.7%
Unknown or Not Reported	1 1.2%	1 2.3%	2 1.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 3.5%	2 4.7%	5 3.9%
Native Hawaiian or Other Pacific Islander	1 1.2%	0 0%	1 0.8%
Black or African American	11 12.9%	10 23.3%	21 16.4%
White	68 80%	31 72.1%	99 77.3%
More than one race	1 1.2%	0 0%	1 0.8%
Unknown or Not Reported	1 1.2%	0 0%	1 0.8%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response
Description	Pathologic complete response was defined as no residual invasive cancer in the breast, after 12 or 24 weeks of lapatinib/trastuzumab with or without endocrine therapy. This outcome is based on patient's pathological report. We are not measuring the clinical response. Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable.
Time Frame	12 or 24 week depending the arm assignment

Outcome Measure Data

Analysis Population Description

Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participant were not evaluable: 3 participant were found ineligible for the study and one participant died before surgery.

Arm/Group Title	24-week Arm	12-week Arm
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Measure Participants	81	43
pathologic complete response	20 23.5%	5 11.6%
non-complete pathologic response	61 71.8%	38 88.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	24-week Arm
	Comments	The study was planned to enroll 136 patients if the original cohort (n=90) was deemed successful. The 24 weeks arm ran as a single arm, using an admissible Simon-like two-stage design. The 12 weeks arm accrued as long as the 24 weeks arm is open. The analysis of the first cohort indicated that 15 pCR were observed , which did not meet the required 20 or more responses. The accrual was closed early and the study has a total of 128 participants.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of pCR
	Estimated Value	0.25
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	No comparison is required between the 24 weeks arm and 12 weeks arm. The study is designed as the 24 weeks arm ran as a single arm, using an admissible Simon-like two-stage design and required 20 or more responses in the first 55 evaluable patients.

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy
Time Frame	12 week or 24 weeks depending on arm assignment

Outcome Measure Data

Analysis Population Description

Participants who started the study treatment will be evaluable for safety analysis

Arm/Group Title	24-week Arm	12-week Arm
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Measure Participants	85	43
Number [participants]	61 71.8%	26 60.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	24-week Arm
	Comments	This outcome is to establish the safety and tolerability of an extended regimen of lapatinib + trastuzumab, with or without endocrine therapy. No comparison between the 2 arms is required.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of patients with AE
	Estimated Value	0.72
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	61 out of 85 patients (72%) in the 24-week arm had at least 1 adverse events.

3. Secondary Outcome

Title	Total Pathologic Complete Response
Description	pathologic complete response was defined as no residual invasive cancer in the breast and the axillary lymph nodes.
Time Frame	12 weeks or 24 weeks depending on arm assignment

Outcome Measure Data

Analysis Population Description

Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participant were not evaluable: 3 participant were found ineligible for the study and one participant died before surgery.

Arm/Group Title	24-week Arm	12-week Arm
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Measure Participants	81	43
total complete pathologic response	8 9.4%	2 4.7%
not total complete pathologic response	72 84.7%	41 95.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	24-week Arm
	Comments	No comparison between the two arms is required.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of tpCR in 24 weeks arm
	Estimated Value	0.1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Response
Time Frame	12 weeks or 24 weeks depending on arm assignment

Outcome Measure Data

Analysis Population Description

Participants who have received at least one cycle of therapy (defined as one dose of trastuzumab and 21 days of lapatinib), and have had their response classified were evaluable. 4 participants were not evaluable for efficacy.

Arm/Group Title	24-week Arm	12-week Arm
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks	Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
Measure Participants	81	43
Complete response	46 54.1%	21 48.8%
Partial response	10 11.8%	13 30.2%
Stable disease	2 2.4%	3 7%
Progressive disease	13 15.3%	4 9.3%
Unknown	10 11.8%	2 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	24-week Arm
	Comments	No comparison between the 2 arm is required for this study.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of CR+PR in 24 weeks arm
	Estimated Value	0.69
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	7 months
Adverse Event Reporting Description	Adverse events experienced by participants will be collected and reported from initiation of study medication, throughout the study, and within 30 days of the last dose of study medication.
Arm/Group Title	24-week Arm		12-week Arm
Arm/Group Description	Participants will receive 24-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks		Participants will receive 12-weeks of lapatinib plus trastuzumab. Participants who are estrogen receptor (ER) and/or progesterone receptor (PR) positive will also receive endocrine therapy. Lapatinib: 1000 mg by mouth daily Letrozole: 2.5 mg by mouth daily (for hormone receptor positive participants only) Trastuzumab: 6 mg/kg intravenously, every 3 weeks
All Cause Mortality
	24-week Arm		12-week Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	24-week Arm		12-week Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/85 (3.5%)		1/43 (2.3%)
Cardiac disorders
Cardiac arrest	1/85 (1.2%)	1	0/43 (0%)	0
Hepatobiliary disorders
Elevated AST	1/85 (1.2%)	1	0/43 (0%)	0
Infections and infestations
Breast infection	1/85 (1.2%)	1	0/43 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/85 (0%)	0	1/43 (2.3%)	1
Hematuria	0/85 (0%)	0	1/43 (2.3%)	1
Renal calculi	0/85 (0%)	0	1/43 (2.3%)	1
Urinary retention	0/85 (0%)	0	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	24-week Arm		12-week Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/85 (71.8%)		26/43 (60.5%)
Blood and lymphatic system disorders
Anemia	8/85 (9.4%)	16	4/43 (9.3%)	11
Gastrointestinal disorders
Diarrhea	30/85 (35.3%)	51	14/43 (32.6%)	22
Mucositis oral	9/85 (10.6%)	15	10/43 (23.3%)	10
Vomiting	6/85 (7.1%)	11	2/43 (4.7%)	2
General disorders
Fatigue	14/85 (16.5%)	19	8/43 (18.6%)	8
Nusea	11/85 (12.9%)	15	6/43 (14%)	6
Pain	5/85 (5.9%)	6	2/43 (4.7%)	2
Investigations
Alanine aminotransferase increased	22/85 (25.9%)	54	5/43 (11.6%)	7
Alkaline phosphatase increased	12/85 (14.1%)	17	3/43 (7%)	3
Aspartate aminotransferase increased	23/85 (27.1%)	46	7/43 (16.3%)	7
Blood bilirubin increased	8/85 (9.4%)	15	0/43 (0%)	0
Metabolism and nutrition disorders
Anorexia	8/85 (9.4%)	10	3/43 (7%)	3
Nervous system disorders
Dysgeusia	4/85 (4.7%)	4	4/43 (9.3%)	4
Headache	5/85 (5.9%)	5	2/43 (4.7%)	2
Psychiatric disorders
Anxiety	4/85 (4.7%)	4	3/43 (7%)	3
Insomnia	7/85 (8.2%)	7	4/43 (9.3%)	4
Skin and subcutaneous tissue disorders
Alopecia	3/85 (3.5%)	3	4/43 (9.3%)	4
Dry skin	8/85 (9.4%)	9	2/43 (4.7%)	2
Pruritus	5/85 (5.9%)	5	3/43 (7%)	3
Rash acneiform	17/85 (20%)	22	5/43 (11.6%)	5
Vascular disorders
Hot flashes	8/85 (9.4%)	8	4/43 (9.3%)	4

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.