Study of Nivolumab in Combination With Gemcitabine/Cisplatin or Ipilimumab for Patients With Advanced Unresectable Biliary Tract Cancer

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03101566
• Collaborator: (none)
• Enrollment: 75
• Locations: 7
• Arms: 2
• Anticipated Duration (Months): 53.3
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this trial is to evaluate the effect of investigational drug nivolumab in combination with either gemcitabine/cisplatin chemotherapy, or in combination with another investigational agent ipilimumab in patients with advanced unresectable biliary tract cancer.

Gemcitabine/cisplatin is the standard of care treatment for biliary tract cancer.

Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab (Opdivo) is FDA approved for the treatment of several cancers including metastatic melanoma, advanced lung, kidney, head & neck and bladder cancer. The combination of nivolumab and ipilimumab (Yervoy) is FDA approved for metastatic melanoma.

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Neoplasms	Drug: Gemcitabine; Drug: Cisplatin; Drug: Ipilimumab; Drug: Nivolumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Randomized Phase II Study of Nivolumab in Combination With Gemcitabine/Cisplatin or Ipilimumab as First Line Therapy for Patients With Advanced Unresectable Biliary Tract Cancer [CA209-9FC]
• Actual Study Start Date: Sep 8, 2017
• Actual Primary Completion Date: Dec 3, 2019
• Anticipated Study Completion Date: Feb 15, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine + Cisplatin + Nivolumab Drug: Gemcitabine 1000 mg/m2 IV on days 1,8 every 3 weeks Drug: Cisplatin 25 mg/m2 IV on days 1,8 every 3 weeks Drug: Nivolumab 360 mg IV on day 1 every 3 weeks If there is continued benefit after 6 months, then: Drug: Nivolumab 240 mg IV on day 1 every 2 weeks	Drug: Gemcitabine; Gemcitabine 1000 mg/m2 IV; Drug: Cisplatin; Cisplatin 25 mg/m2 IV; Drug: Nivolumab; Nivolumab 360 mg or 240 mg IV
Experimental: Nivolumab + Ipilimumab Drug: Ipilimumab 1 mg/kg IV on day 1 every 6 weeks Drug: Nivolumab 240 mg IV on day 1 every 2 weeks	Drug: Ipilimumab; Ipilimumab 1 mg/kg IV; Drug: Nivolumab; Nivolumab 360 mg or 240 mg IV

Outcome Measures

Primary Outcome Measures

1. The Percentage of Patients Alive and Without Progression at 6 Months Following the Initiation of Treatment [6 Months]

   The primary endpoint is PFS (Progression Free Survival) at 6 months following the initiation of treatment. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition.

Secondary Outcome Measures

1. Median Progression Free Survival Time [Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest]

   The median time patients are alive without progression following the initiation of treatment wherein progression will be defined clinically or on imaging as per irRECIST criteria.

2. Median Overall Survival Time [Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest]

   The median overall survival time following the initiation of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have a pathologically confirmed adenocarcinoma of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gall bladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed histology are excluded.

• Patients may have received prior radiation, chemoembolization, radioembolization or other local ablative therapies or hepatic resection if completed ≥ 4 weeks prior to registration AND if patient has recovered to <= grade 1 toxicity. Extrahepatic palliative radiation is permitted if completed ≥ 2 weeks prior to enrollment AND if patient has recovered to ≤ grade 1 toxicity.

• Patients must have radiographically measurable disease in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site.

• Must be ≥18 years of age

• Must have a Child-Pugh score of A (prognosis in chronic liver disease and cirrhosis)

• Must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0-1

• Ability to understand and willingness to sign IRB-approved informed consent

• Willing to provide archived tissue, if available, from a previous diagnostic biopsy

• Must be able to tolerate CT (computerized tomography) and/or MRI (magnetic resonance imaging) with contrast

• Must have adequate organ function obtained ≤ 2 weeks prior to registration

Exclusion Criteria:

• Patients may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC (biliary tract cancer). Prior adjuvant chemotherapy is permitted provided it was completed > 6 months from registration.

• Must not have a diagnosis of immunodeficiency, or have received systemic steroid therapy, or any other form of immunosuppressive therapy within 7 days prior to trial treatment.

• Must not have known Hepatitis B, Hepatitis C, or HIV seropositivity. Testing is not required in absence of clinical suspicion.

• Must not have prior history of organ transplantation or brain metastasis.

• Must not have undergone a major surgical procedure < 4 weeks prior to registration.

• Must not have an active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ. Patients with history of malignancy are eligible provided primary treatment of that cancer was completed > 1 year prior to registration and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy.

• Must have no ongoing active, uncontrolled infections

• Must not have received a live vaccine within 30 days of planned start of the study therapy.

• Must not have a psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements.

• Women must not be pregnant or breastfeeding since study drugs may harm the fetus or child.

• Women of child-bearing potential and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation and for 5 months (for women) and 7 months (for men) following completion of study therapy.

• Participants with an active, known or suspected autoimmune disease which may affect vital organ function, or has/may require systemic immunosuppressive therapy for management are excluded. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30322
2	Northwestern University	Chicago	Illinois	United States	60611
3	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
4	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
5	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
6	University of Washington	Seattle	Washington	United States	98109
7	University of Wisconsin	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Vaibhav Sahai, MBBS, MS, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 28, 2018

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT03101566
• Other Study ID Numbers: UMCC 2017.026; HUM00126271; HUM00130035
• First Posted: Apr 5, 2017
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 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
• Additional relevant MeSH terms: Biliary Tract Neoplasms; Gemcitabine; Nivolumab; Ipilimumab

Study Results

Participant Flow

Arm/Group Title	Gemcitabine + Cisplatin + Nivolumab	Nivolumab + Ipilimumab
Arm/Group Description	Gemcitabine1000 mg/m2 IV and Cisplatin 25 mg/m2 IV on days 1 and 8 every 3 weeks + Nivolumab 360 mg IV on day 1 every 3 weeks for up to 8, 3-week cycles. Followed by Nivolumab alone at 240 mg IV every 2 weeks. Total duration no longer than 2 years of study treatment.	Nivolumab 240 mg IV on day 1 every 2 weeks + Ipilimumab 1 mg/kg IV on day 1 every 6 weeks; for up to 2 years in absence of disease progression.
Period Title: Overall Study
STARTED	37	38
Received at Least One Dose of Protocol Therapy	35	33
Assessed for Primary and Secondary Progression-free Survival	32	33
COMPLETED	31	31
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Gemcitabine + Cisplatin + Nivolumab	Nivolumab + Ipilimumab	Total
Arm/Group Description	Gemcitabine1000 mg/m2 IV and Cisplatin 25 mg/m2 IV on days 1 and 8 every 3 weeks + Nivolumab 360 mg IV on day 1 every 3 weeks for up to 8, 3-week cycles. Followed by Nivolumab alone at 240 mg IV every 2 weeks. Total duration no longer than 2 years of study treatment.	Nivolumab 240 mg IV on day 1 every 2 weeks + Ipilimumab 1 mg/kg IV on day 1 every 6 weeks; for up to 2 years in absence of disease progression.	Total of all reporting groups
Overall Participants	37	38	75
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59	61	60
Sex: Female, Male (Count of Participants)
Female	17 45.9%	20 52.6%	37 49.3%
Male	20 54.1%	18 47.4%	38 50.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 16.2%	1 2.6%	7 9.3%
Not Hispanic or Latino	31 83.8%	36 94.7%	67 89.3%
Unknown or Not Reported	0 0%	1 2.6%	1 1.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	4 10.5%	4 5.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 10.8%	4 10.5%	8 10.7%
White	32 86.5%	28 73.7%	60 80%
More than one race	0 0%	1 2.6%	1 1.3%
Unknown or Not Reported	1 2.7%	1 2.6%	2 2.7%
Disease status at enrollment (Count of Participants)
locally advanced	4 10.8%	4 10.5%	8 10.7%
metastatic	33 89.2%	34 89.5%	67 89.3%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Patients Alive and Without Progression at 6 Months Following the Initiation of Treatment
Description	The primary endpoint is PFS (Progression Free Survival) at 6 months following the initiation of treatment. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine + Cisplatin + Nivolumab	Nivolumab + Ipilimumab
Arm/Group Description	Gemcitabine1000 mg/m2 IV and Cisplatin 25 mg/m2 IV on days 1 and 8 every 3 weeks + Nivolumab 360 mg IV on day 1 every 3 weeks for up to 8, 3-week cycles. Followed by Nivolumab alone at 240 mg IV every 2 weeks. Total duration no longer than 2 years of study treatment.	Nivolumab 240 mg IV on day 1 every 2 weeks + Ipilimumab 1 mg/kg IV on day 1 every 6 weeks; for up to 2 years in absence of disease progression.
Measure Participants	32	33
Number (95% Confidence Interval) [percentage of participants]	59.4 160.5%	21.2 55.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gemcitabine + Cisplatin + Nivolumab, Nivolumab + Ipilimumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		PFS at 6 months was estimated for this trial using the product-limit method of Kaplan and Meier with 95% confidence intervals calculated using Greenwood's formula. All statistical analyses were completed using the SAS System, v9.4 [Cary, NC, USA].

2. Secondary Outcome

Title	Median Progression Free Survival Time
Description	The median time patients are alive without progression following the initiation of treatment wherein progression will be defined clinically or on imaging as per irRECIST criteria.
Time Frame	Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Median Overall Survival Time
Description	The median overall survival time following the initiation of treatment.
Time Frame	Patients will be followed until death, withdrawal from study, or until 2 years, whichever is earliest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Data on adverse events was collected from the time of the initial study treatment administration through 100 days after the last dose of study treatment. Any serious adverse event that occured more than 100 days after the last study treatment and is considered related to the study treatment or intervention is also reported.
Arm/Group Title	Gemcitabine + Cisplatin + Nivolumab		Nivolumab + Ipilimumab
Arm/Group Description	Gemcitabine1000 mg/m2 IV and Cisplatin 25 mg/m2 IV on days 1 and 8 every 3 weeks + Nivolumab 360 mg IV on day 1 every 3 weeks for up to 8, 3-week cycles. Followed by Nivolumab alone at 240 mg IV every 2 weeks. Total duration no longer than 2 years of study treatment.		Nivolumab 240 mg IV on day 1 every 2 weeks + Ipilimumab 1 mg/kg IV on day 1 every 6 weeks; for up to 2 years in absence of disease progression.
All Cause Mortality
	Gemcitabine + Cisplatin + Nivolumab		Nivolumab + Ipilimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/35 (62.9%)		23/33 (69.7%)
Serious Adverse Events
	Gemcitabine + Cisplatin + Nivolumab		Nivolumab + Ipilimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/35 (71.4%)		23/33 (69.7%)
Blood and lymphatic system disorders
Leukocytosis	1/35 (2.9%)	1	0/33 (0%)	0
Anemia	0/35 (0%)	0	1/33 (3%)	1
Cardiac disorders
Paroxysmal atrial tachycardia	1/35 (2.9%)	1	0/33 (0%)	0
Myocardial infarction	0/35 (0%)	0	1/33 (3%)	1
Sinus tachycardia	0/35 (0%)	0	1/33 (3%)	1
Endocrine disorders
Adrenal insufficiency	0/35 (0%)	0	1/33 (3%)	1
Gastrointestinal disorders
Abdominal distension	1/35 (2.9%)	1	1/33 (3%)	2
Abdominal pain	5/35 (14.3%)	5	3/33 (9.1%)	3
Ascites	1/35 (2.9%)	1	0/33 (0%)	0
Constipation	1/35 (2.9%)	1	0/33 (0%)	0
Enterocolitis	1/35 (2.9%)	1	0/33 (0%)	0
Nausea	1/35 (2.9%)	2	1/33 (3%)	2
Upper gastrointestinal hemorrhage	1/35 (2.9%)	1	1/33 (3%)	1
Colitis	0/35 (0%)	0	1/33 (3%)	1
Colonic perforation	0/35 (0%)	0	1/33 (3%)	1
Diarrhea	0/35 (0%)	0	2/33 (6.1%)	2
Vomiting	0/35 (0%)	0	1/33 (3%)	1
General disorders
Fever	4/35 (11.4%)	4	1/33 (3%)	1
Chills	0/35 (0%)	0	1/33 (3%)	1
Fatigue	0/35 (0%)	0	1/33 (3%)	1
Infusion related reaction	0/35 (0%)	0	1/33 (3%)	1
Hepatobiliary disorders
Bile duct stenosis	2/35 (5.7%)	2	1/33 (3%)	1
Cholecystitis	2/35 (5.7%)	3	1/33 (3%)	1
Hepatobiliary disorders - Other	1/35 (2.9%)	1	1/33 (3%)	1
Infections and infestations
Infections and infestations - Other	3/35 (8.6%)	4	3/33 (9.1%)	4
Sepsis	4/35 (11.4%)	6	2/33 (6.1%)	3
Small intestine infection	1/35 (2.9%)	1	0/33 (0%)	0
Encephalitis infection	0/35 (0%)	0	1/33 (3%)	1
Lung infection	0/35 (0%)	0	1/33 (3%)	1
Injury, poisoning and procedural complications
Fall	0/35 (0%)	0	1/33 (3%)	1
Postoperative hemorrhage	0/35 (0%)	0	1/33 (3%)	1
Investigations
Alanine aminotransferase increased	1/35 (2.9%)	1	0/33 (0%)	0
Aspartate aminotransferase increased	1/35 (2.9%)	1	0/33 (0%)	0
Blood bilirubin increased	1/35 (2.9%)	3	4/33 (12.1%)	4
Investigations - Other	0/35 (0%)	0	1/33 (3%)	1
Metabolism and nutrition disorders
Dehydration	1/35 (2.9%)	1	2/33 (6.1%)	2
Hypercalcemia	1/35 (2.9%)	1	0/33 (0%)	0
Hyperkalemia	1/35 (2.9%)	1	0/33 (0%)	0
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	0/35 (0%)	0	1/33 (3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	5/35 (14.3%)	5	6/33 (18.2%)	6
Nervous system disorders
Nervous system disorders - Other, specify	1/35 (2.9%)	1	0/33 (0%)	0
Syncope	1/35 (2.9%)	1	0/33 (0%)	0
Psychiatric disorders
Confusion	1/35 (2.9%)	1	1/33 (3%)	1
Renal and urinary disorders
Acute kidney injury	1/35 (2.9%)	1	0/33 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/35 (2.9%)	1	0/33 (0%)	0
Pleural effusion	2/35 (5.7%)	2	0/33 (0%)	0
Pneumonitis	0/35 (0%)	0	1/33 (3%)	1
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/35 (2.9%)	1	0/33 (0%)	0
Vascular disorders
Hypotension	1/35 (2.9%)	1	1/33 (3%)	1
Thromboembolic event	3/35 (8.6%)	3	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine + Cisplatin + Nivolumab		Nivolumab + Ipilimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/35 (97.1%)		28/33 (84.8%)
Blood and lymphatic system disorders
Anemia	16/35 (45.7%)		5/33 (15.2%)
Cardiac disorders
Sinus tachycardia	2/35 (5.7%)		0/33 (0%)
Ear and labyrinth disorders
Tinnitus	3/35 (8.6%)		0/33 (0%)
Endocrine disorders
Hypothyroidism	1/35 (2.9%)		3/33 (9.1%)
Eye disorders
Papilledema	2/35 (5.7%)		0/33 (0%)
Gastrointestinal disorders
Abdominal pain	14/35 (40%)		11/33 (33.3%)
Ascites	1/35 (2.9%)		5/33 (15.2%)
Bloating	2/35 (5.7%)		1/33 (3%)
Constipation	13/35 (37.1%)		10/33 (30.3%)
Diarrhea	13/35 (37.1%)		8/33 (24.2%)
Dyspepsia	0/35 (0%)		2/33 (6.1%)
Dysphagia	2/35 (5.7%)		1/33 (3%)
Flatulence	3/35 (8.6%)		1/33 (3%)
Gastritis	2/35 (5.7%)		0/33 (0%)
Gastroesophageal reflux disease	1/35 (2.9%)		3/33 (9.1%)
Mucositis oral	2/35 (5.7%)		0/33 (0%)
Nausea	18/35 (51.4%)		9/33 (27.3%)
Vomiting	10/35 (28.6%)		5/33 (15.2%)
General disorders
Chills	3/35 (8.6%)		2/33 (6.1%)
Edema limbs	8/35 (22.9%)		8/33 (24.2%)
Fatigue	15/35 (42.9%)		16/33 (48.5%)
Fever	7/35 (20%)		4/33 (12.1%)
Flu like symptoms	1/35 (2.9%)		3/33 (9.1%)
Infusion related reaction	0/35 (0%)		2/33 (6.1%)
Non-cardiac chest pain	4/35 (11.4%)		0/33 (0%)
Pain	7/35 (20%)		5/33 (15.2%)
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	1/35 (2.9%)		2/33 (6.1%)
Infections and infestations
Infections and infestations - Other, specify	4/35 (11.4%)		4/33 (12.1%)
Injury, poisoning and procedural complications
Fall	1/35 (2.9%)		2/33 (6.1%)
Investigations
Alanine aminotransferase increased	8/35 (22.9%)		5/33 (15.2%)
Alkaline phosphatase increased	7/35 (20%)		6/33 (18.2%)
Aspartate aminotransferase increased	5/35 (14.3%)		4/33 (12.1%)
Blood bilirubin increased	2/35 (5.7%)		6/33 (18.2%)
Creatinine increased	3/35 (8.6%)		3/33 (9.1%)
Investigations - Other, specify	0/35 (0%)		2/33 (6.1%)
Lipase increased	2/35 (5.7%)		1/33 (3%)
Lymphocyte count decreased	4/35 (11.4%)		2/33 (6.1%)
Neutrophil count decreased	14/35 (40%)		0/33 (0%)
Platelet count decreased	11/35 (31.4%)		0/33 (0%)
Weight gain	1/35 (2.9%)		2/33 (6.1%)
Weight loss	7/35 (20%)		6/33 (18.2%)
White blood cell decreased	8/35 (22.9%)		0/33 (0%)
Metabolism and nutrition disorders
Anorexia	5/35 (14.3%)		9/33 (27.3%)
Dehydration	6/35 (17.1%)		1/33 (3%)
Hypercalcemia	2/35 (5.7%)		0/33 (0%)
Hyperglycemia	2/35 (5.7%)		3/33 (9.1%)
Hypoalbuminemia	8/35 (22.9%)		2/33 (6.1%)
Hypocalcemia	2/35 (5.7%)		1/33 (3%)
Hypokalemia	4/35 (11.4%)		2/33 (6.1%)
Hypomagnesemia	9/35 (25.7%)		0/33 (0%)
Hyponatremia	4/35 (11.4%)		7/33 (21.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/35 (2.9%)		2/33 (6.1%)
Back pain	7/35 (20%)		5/33 (15.2%)
Musculoskeletal and connective tissue disorder - Other, specify	1/35 (2.9%)		2/33 (6.1%)
Pain in extremity	3/35 (8.6%)		1/33 (3%)
Nervous system disorders
Dizziness	3/35 (8.6%)		2/33 (6.1%)
Dysgeusia	2/35 (5.7%)		0/33 (0%)
Headache	4/35 (11.4%)		2/33 (6.1%)
Peripheral sensory neuropathy	4/35 (11.4%)		2/33 (6.1%)
Psychiatric disorders
Anxiety	1/35 (2.9%)		4/33 (12.1%)
Depression	2/35 (5.7%)		0/33 (0%)
Insomnia	2/35 (5.7%)		4/33 (12.1%)
Respiratory, thoracic and mediastinal disorders
Cough	4/35 (11.4%)		3/33 (9.1%)
Dyspnea	7/35 (20%)		6/33 (18.2%)
Hiccups	3/35 (8.6%)		0/33 (0%)
Hoarseness	2/35 (5.7%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders - Other, specify	2/35 (5.7%)		0/33 (0%)
Skin and subcutaneous tissue disorders
Alopecia	2/35 (5.7%)		0/33 (0%)
Dry skin	3/35 (8.6%)		1/33 (3%)
Pruritus	2/35 (5.7%)		3/33 (9.1%)
Rash acneiform	2/35 (5.7%)		1/33 (3%)
Rash maculo-papular	4/35 (11.4%)		8/33 (24.2%)
Vascular disorders
Hot flashes	1/35 (2.9%)		2/33 (6.1%)
Hypertension	5/35 (14.3%)		0/33 (0%)
Hypotension	3/35 (8.6%)		1/33 (3%)
Phlebitis	2/35 (5.7%)		0/33 (0%)
Thromboembolic event	2/35 (5.7%)		3/33 (9.1%)

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.