Hedgehog Inhibitors for Metastatic Adenocarcinoma of the Pancreas

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT01088815
• Collaborator: Stand Up To Cancer (Other), Genentech, Inc. (Industry), Celgene Corporation (Industry)
• Enrollment: 98
• Locations: 3
• Arm: 1
• Actual Duration (Months): 89
• Patients Per Site: 32.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is an open-label, single arm, multi-center, Phase II trial to evaluate the progression free survival in patients with metastatic adenocarcinoma of the pancreas treated with a hedgehog inhibitor (GDC-0449) in combination with chemotherapy (gemcitabine and nab-Paclitaxel).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Cancer	Drug: Gemcitabine, nab-Paclitaxel, GDC-0449	Phase 2

Detailed Description

The emergence of new small molecules with capacity of blocking the Hedgehog signaling pathway provides a novel therapeutic approach in pancreatic adenocarcinoma treating the primary tumor, stroma, systemic metastases and pancreatic cancer stem cells by hedgehog pathway inhibition. This phase 2 clinical trial will evaluate the progression free survival (PFS) in patients with previously untreated metastatic pancreatic adenocarcinoma. We hypothesize that the combination of cytotoxic agents (gemcitabine and nab-paclitaxel) with the Hedgehog inhibitor GDC-0449 may increase PFS.

This study includes correlative studies to attempt to understand the stem cell biology and mechanism for any observed clinical benefits with the use of Hedgehog inhibitor GDC-0449. These include changes in the hedgehog pathway and changes in pancreatic cancer stem cell markers with pre and post treatment biopsies. The safety of GDC-0449 when combined with chemotherapy gemcitabine and nab-paclitaxel will also be assessed by evaluating adverse event rate.

Following the determination of eligibility patients will receive the following treatment:

1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then

2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily

Patients may continue on treatment regimen until they experience progressive disease or unacceptable toxicity, require palliative radiotherapy, withdraw consent or the physician feels it is not longer in their best interest to continue on treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Gemcitabine and Nab-Paclitaxel in Combination With GDC-0449 (Hedgehog Inhibitor) in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas
• Actual Study Start Date: Sep 17, 2010
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Feb 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine, nab-paclitaxel, GDC-0449 Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib)	Drug: Gemcitabine, nab-Paclitaxel, GDC-0449; One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival With the Combination of GDC-0449 With Gemcitabine and Nab-paclitaxel. [6 years]

   Number of months from time first therapy received to the earliest documented disease progression or death from any cause.

2. Safety of Combination Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas as Assessed by Number of Grade 3 or 4 Adverse Events [6 years]

   Number of grade 3 or 4 adverse events as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v4.0) that occur after Cycle 2, Day 1

Secondary Outcome Measures

1. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Overall Survival [6 years]

   Total number of months alive.

2. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Tumor Response [6 years]

   Number of participants with complete (CR) or partial (PR) response as defined by RECIST criteria.

3. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Changes in Pancreatic Cancer Stem Cell [6 years]

   Change in number of Pancreatic cancer stem cells in tissue and peripheral blood in tissue biopsy and peripheral blood.

4. Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Hedgehog Signaling Pathway Downregulation [6 years]

   Hedgehog signaling pathway downregulation as measured by Gli-1 and Patch expression

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cells tumors are excluded. Biopsy within 14 days of starting treatment.

2. Patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.

3. Patient has NOT received previous radiotherapy, surgery or chemotherapy or investigational drug therapy for the treatment of metastatic disease. If the patient received radiotherapy, chemotherapy or investigational therapy in the adjuvant setting it should be completed 3 weeks prior to enrollment. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least six months after completing the last dose of gemcitabine

4. Age >18 years.

5. Life expectancy of greater than 1 month.

6. ECOG performance status 0 or 1 (Karnofsky >70%).

7. Patients must have adequate organ and marrow function

Exclusion Criteria:

1. Patient had received chemotherapy or radiotherapy for metastatic disease

2. Patient is receiving other investigational agents.

3. Patient has known brain metastases, unless previously treated and well controlled for at least three months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)

4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study.

5. Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.

6. Uncontrolled illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure not controlled with medication, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

7. Pregnant women are excluded

8. Patient has undergone a major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ) within four weeks prior to Day 1 of treatment on this study.

9. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Translational Genomics Research Institute (TGen)	Scottsdale	Arizona	United States	85258
2	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21205
3	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Stand Up To Cancer
• Genentech, Inc.
• Celgene Corporation

Investigators

• Principal Investigator: Daniel Laheru, MD, Sidney Kimmel Comprehensive Cancer Center JHMI
• Principal Investigator: Ana De Jesus-Acosta, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 4, 2014

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01088815
• Other Study ID Numbers: J1013; NA_00036883
• First Posted: Mar 17, 2010
• Last Update Posted: Apr 26, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Adenocarcinoma; Hedgehog; Neoplasms; Digestive System Diseases; Neoplasms by Site; Digestive System Neoplasms; Neoplasms by Histologic Type; Pancreatic Neoplasms; Pancreatic Diseases; Carcinoma
• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Paclitaxel

Study Results

Participant Flow

Pre-assignment Detail	98 subjects signed consents in total. 26 subjects were screen-fails

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Period Title: Overall Study
STARTED	72
COMPLETED	72
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Overall Participants	72
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	40 55.6%
>=65 years	32 44.4%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62.05
Sex: Female, Male (Count of Participants)
Female	35 48.6%
Male	37 51.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	71 98.6%
Unknown or Not Reported	1 1.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 6.9%
White	64 88.9%
More than one race	0 0%
Unknown or Not Reported	1 1.4%
Region of Enrollment (Count of Participants)
United States	72 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival With the Combination of GDC-0449 With Gemcitabine and Nab-paclitaxel.
Description	Number of months from time first therapy received to the earliest documented disease progression or death from any cause.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was evaluable in only in 67/72 participants.

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Measure Participants	67
Median (95% Confidence Interval) [months]	5.42

2. Primary Outcome

Title	Safety of Combination Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas as Assessed by Number of Grade 3 or 4 Adverse Events
Description	Number of grade 3 or 4 adverse events as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v4.0) that occur after Cycle 2, Day 1
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Measure Participants	72
Number [Grade 3/4 adverse events]	104

3. Secondary Outcome

Title	Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Overall Survival
Description	Total number of months alive.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Data was evaluable in only 67/72 participants for this outcome measure

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Measure Participants	67
Median (95% Confidence Interval) [months]	9.79

4. Secondary Outcome

Title	Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Tumor Response
Description	Number of participants with complete (CR) or partial (PR) response as defined by RECIST criteria.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Data was evaluable in only 67/72 participants for this outcome measure

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Measure Participants	67
CR	1 1.4%
PR	26 36.1%

5. Secondary Outcome

Title	Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Changes in Pancreatic Cancer Stem Cell
Description	Change in number of Pancreatic cancer stem cells in tissue and peripheral blood in tissue biopsy and peripheral blood.
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Peripheral blood data was collected from only 57/72 participants. Tissue biopsy data was not evaluable for analysis due to inadequate biopsy samples for all 23/72 participants who underwent biopsy

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Measure Participants	72
peripheral blood	27.0 (4.0)

6. Secondary Outcome

Title	Efficacy of Combination of GDC-0449 With Gemcitabine and Nab-Paclitaxel as Assessed by Hedgehog Signaling Pathway Downregulation
Description	Hedgehog signaling pathway downregulation as measured by Gli-1 and Patch expression
Time Frame	6 years

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
Measure Participants	0

Adverse Events

Time Frame	6 years
Arm/Group Title	Gemcitabine, Nab-paclitaxel, GDC-0449
Arm/Group Description	Gemcitabine and nab-Paclitaxel in combination with GDC-0449 (Vismodegib) Gemcitabine, nab-Paclitaxel, GDC-0449: 1. One cycle of Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 (28 days cycle) then 2. Gemcitabine 1000 mg/m2 and nab-Paclitaxel 125 mg/m2 on days 1, 8, and 15 every 28 days cycle in combination with oral GDC-0449 150 mg daily
All Cause Mortality
	Gemcitabine, Nab-paclitaxel, GDC-0449
	Affected / at Risk (%)	# Events
Total	64/72 (88.9%)
Serious Adverse Events
	Gemcitabine, Nab-paclitaxel, GDC-0449
	Affected / at Risk (%)	# Events
Total	46/72 (63.9%)
Blood and lymphatic system disorders
Abdominal Distension	1/72 (1.4%)	1
Febrile Neutropenia	2/72 (2.8%)	2
Anemia	3/72 (4.2%)	3
Blood Bilirubin Increased	1/72 (1.4%)	1
Blood/Lymph Disorder	1/72 (1.4%)	1
Cardiac disorders
Atrial Fibrillation	1/72 (1.4%)	1
Heart Failure	1/72 (1.4%)	1
Myocardial Infarction	1/72 (1.4%)	1
Pericardial Effusion	1/72 (1.4%)	1
Eye disorders
Ileus	1/72 (1.4%)	2
Gastrointestinal disorders
Abdominal Pain	2/72 (2.8%)	2
Ascites	1/72 (1.4%)	1
Diarrhea	1/72 (1.4%)	1
Duodenal Obstruction	1/72 (1.4%)	1
Gallbladder Infection	1/72 (1.4%)	1
Gastroparesis	1/72 (1.4%)	1
GI disorders	2/72 (2.8%)	3
Nausea	1/72 (1.4%)	1
Obstruction Gastric	1/72 (1.4%)	1
Small Intestinal Obstruction	1/72 (1.4%)	1
Upper GI Hemorrhage	2/72 (2.8%)	4
Vomiting	2/72 (2.8%)	2
General disorders
Death	5/72 (6.9%)	5
Fatigue	1/72 (1.4%)	1
Fever	8/72 (11.1%)	9
General Disorders/Administration Site	1/72 (1.4%)	1
Hepatobiliary disorders
Hepatobil Disorders	4/72 (5.6%)	4
Infections and infestations
Infestion/Infestation-Other	2/72 (2.8%)	2
Sepsis	6/72 (8.3%)	6
Splenic Infection	1/72 (1.4%)	1
Wound Infection	1/72 (1.4%)	1
Investigations
Investigations-Other	4/72 (5.6%)	4
Neutrophil Count Decreased	2/72 (2.8%)	2
Platelet Count Decreased	2/72 (2.8%)	2
Metabolism and nutrition disorders
Dehyrdation	4/72 (5.6%)	4
Hyponatremia	2/72 (2.8%)	2
Musculoskeletal and connective tissue disorders
Pain in Extremity	1/72 (1.4%)	1
Nervous system disorders
Lethargy	1/72 (1.4%)	1
Stroke	1/72 (1.4%)	1
Syncope	1/72 (1.4%)	2
Renal and urinary disorders
Acute Kidney Injury	1/72 (1.4%)	1
Kidney Infection	1/72 (1.4%)	1
Urinary Tract Obstruction	1/72 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/72 (1.4%)	1
Pneumonitis	4/72 (5.6%)	4
Respiratory/Thoracic/Mediastinal Disorder	1/72 (1.4%)	1
Skin and subcutaneous tissue disorders
Skin Infection	4/72 (5.6%)	4
Vascular disorders
Hematoma	2/72 (2.8%)	2
Hypotension	2/72 (2.8%)	2
Thromboembolic	4/72 (5.6%)	4
Vascular Access Complication	1/72 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine, Nab-paclitaxel, GDC-0449
	Affected / at Risk (%)	# Events
Total	72/72 (100%)
Blood and lymphatic system disorders
Anemia	56/72 (77.8%)	232
Blood Bilirubin Increased	12/72 (16.7%)	19
Blood/Lymph Disorder	4/72 (5.6%)	4
Febrile Neutropenia	2/72 (2.8%)	2
Leukocytosis	3/72 (4.2%)	3
Cardiac disorders
Atrial Fibrillation	1/72 (1.4%)	1
Atrial Flutter	1/72 (1.4%)	1
Cardiac Troponin I Increased	1/72 (1.4%)	1
Cardiac Troponin T Increased	1/72 (1.4%)	1
Chest Pain - Cardiac	1/72 (1.4%)	1
ECG QT Corrected int prolong	1/72 (1.4%)	1
Pericardial effusion	6/72 (8.3%)	7
Right ventricular dysfunction	1/72 (1.4%)	2
Sinus tachycardia	1/72 (1.4%)	1
Syncope	2/72 (2.8%)	2
Eye disorders
Dry Eye	1/72 (1.4%)	1
Eye Disorder - Other	2/72 (2.8%)	2
Photophobia	1/72 (1.4%)	1
Watering eyes	1/72 (1.4%)	1
Gastrointestinal disorders
Abdominal Distension	5/72 (6.9%)	5
Abdominal Pain	19/72 (26.4%)	23
Anal Hemorrhage	1/72 (1.4%)	1
Ascites	12/72 (16.7%)	14
Bloating	3/72 (4.2%)	3
Constipation	17/72 (23.6%)	21
Diarrhea	30/72 (41.7%)	43
Dry Mouth	6/72 (8.3%)	8
Duodenal Perforation	1/72 (1.4%)	1
Dyspepsia	2/72 (2.8%)	2
dysphagia	2/72 (2.8%)	3
Esophagitis	1/72 (1.4%)	1
Fecal incontinence	1/72 (1.4%)	1
Flatulence	6/72 (8.3%)	6
Gastric Ulcer	1/72 (1.4%)	1
Gastritis	2/72 (2.8%)	2
GERD	3/72 (4.2%)	3
GI disorders - other	11/72 (15.3%)	14
Hemorrhoidal Hemorrhage	2/72 (2.8%)	2
Hemorrhoids	1/72 (1.4%)	1
Mucositis oral	8/72 (11.1%)	9
Nausea	41/72 (56.9%)	56
Oral dysesthesia	1/72 (1.4%)	1
Oral Pain	1/72 (1.4%)	1
Periodontal disease	1/72 (1.4%)	2
Rectal hemorrhage	1/72 (1.4%)	3
Small intestinal obstruction	1/72 (1.4%)	2
Stomach Pain	2/72 (2.8%)	3
Vomiting	30/72 (41.7%)	40
General disorders
Chills	14/72 (19.4%)	15
Edema Face	1/72 (1.4%)	1
Edema Limbs	28/72 (38.9%)	52
Fatigue	49/72 (68.1%)	97
Fever	22/72 (30.6%)	38
Flu like symptoms	12/72 (16.7%)	16
Gait Disturbance	4/72 (5.6%)	5
General disorders/admin site conditions	5/72 (6.9%)	5
Localized edema	5/72 (6.9%)	5
Malaise	2/72 (2.8%)	4
Pain	11/72 (15.3%)	12
Hepatobiliary disorders
Bile Duct Stenosis	1/72 (1.4%)	1
Hepatobil disorders - other	1/72 (1.4%)	1
Infections and infestations
Infections/Infestactions - Other	10/72 (13.9%)	13
Lung infection	4/72 (5.6%)	4
Mucosal infection	3/72 (4.2%)	4
Sinusitis	5/72 (6.9%)	5
Skin infection	7/72 (9.7%)	11
Wound infection	2/72 (2.8%)	4
Injury, poisoning and procedural complications
Fall	1/72 (1.4%)	1
Infusion site extravasation	1/72 (1.4%)	1
Injection site reaction	1/72 (1.4%)	1
Vascular access complication	1/72 (1.4%)	1
Investigations
Alkaline Phosphatase Increased	23/72 (31.9%)	38
ALT Increased	34/72 (47.2%)	60
APTT Prolonged	4/72 (5.6%)	7
AST Increased	35/72 (48.6%)	53
CD34 Lymphocytes Decreased	1/72 (1.4%)	1
CPK Increased	1/72 (1.4%)	1
Creatinine Increased	9/72 (12.5%)	11
INR Increased	8/72 (11.1%)	10
Investigations-Other, specify	8/72 (11.1%)	12
Lipase increased	2/72 (2.8%)	3
Lymphocyte count decreased	41/72 (56.9%)	175
Lymphocyte count increased	4/72 (5.6%)	4
Neutrophil count decreased	41/72 (56.9%)	138
Platelet count decreased	44/72 (61.1%)	155
Weight gain	3/72 (4.2%)	3
Weight loss	16/72 (22.2%)	26
White blood cell decreased	51/72 (70.8%)	285
Metabolism and nutrition disorders
Alkalosis	1/72 (1.4%)	1
Anorexia	26/72 (36.1%)	37
Dehydration	11/72 (15.3%)	37
Hypercalcemia	1/72 (1.4%)	1
Hyperglycemia	31/72 (43.1%)	65
Hyperkalemia	12/72 (16.7%)	15
Hypermagnesemia	5/72 (6.9%)	6
Hypoalbuminemia	33/72 (45.8%)	91
Hypocalcemia	29/72 (40.3%)	60
Hypoglycemia	3/72 (4.2%)	5
Hypokalemia	20/72 (27.8%)	37
Hypomagnesemia	9/72 (12.5%)	15
Hyponatremia	24/72 (33.3%)	47
Hypophosphatemia	11/72 (15.3%)	19
Metabolism/nutrition disorders-Other	1/72 (1.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	3/72 (4.2%)	3
Back Pain	6/72 (8.3%)	6
Chest Wall Pain	1/72 (1.4%)	1
Flank Pain	3/72 (4.2%)	3
Fracture	2/72 (2.8%)	2
Generalized Muscle Weakness	6/72 (8.3%)	8
Musculoskeletal and connective tissue disorder	12/72 (16.7%)	24
Muscle weakness lower limb	2/72 (2.8%)	2
Myalgia	9/72 (12.5%)	12
Neck Pain	1/72 (1.4%)	1
Non-Cardiac Chest Pain	2/72 (2.8%)	2
Pain in extremity	6/72 (8.3%)	7
Nervous system disorders
Dizziness	18/72 (25%)	18
Dysarthria	1/72 (1.4%)	1
Dysgeusia	53/72 (73.6%)	74
Dysphasia	1/72 (1.4%)	1
Extrapyramidal Disorder	1/72 (1.4%)	1
Facial Nerve Disorder	1/72 (1.4%)	1
Headache	6/72 (8.3%)	8
Intracranial hemorrhage	1/72 (1.4%)	1
Lethargy	2/72 (2.8%)	2
Nervous system disorders - other	6/72 (8.3%)	8
Oculomotor nerve disorder	1/72 (1.4%)	1
Paresthesia	9/72 (12.5%)	17
Peripheral motor neuropathy	16/72 (22.2%)	27
Peripheral sensory neuropathy	36/72 (50%)	77
Presyncope	1/72 (1.4%)	2
Restlessness	1/72 (1.4%)	1
Seizure	1/72 (1.4%)	1
Tremor	1/72 (1.4%)	1
Psychiatric disorders
Agitation	1/72 (1.4%)	1
Anxiety	7/72 (9.7%)	7
Concentration Impairment	1/72 (1.4%)	1
Confusion	4/72 (5.6%)	7
Depression	6/72 (8.3%)	6
Hallucinations	1/72 (1.4%)	1
Insomnia	6/72 (8.3%)	6
Psych disorders-Other, spec	1/72 (1.4%)	1
Renal and urinary disorders
Hematuria	2/72 (2.8%)	2
Hemoglobinuria	1/72 (1.4%)	1
Proteinuria	5/72 (6.9%)	6
Renal/urinary disorders-Other	4/72 (5.6%)	5
Urinary frequency	1/72 (1.4%)	1
Urinary retention	2/72 (2.8%)	2
Urinary tract infection	4/72 (5.6%)	4
Urine discoloration	1/72 (1.4%)	1
Reproductive system and breast disorders
Breast Pain	1/72 (1.4%)	1
Genital Edema	3/72 (4.2%)	3
Prostatic obstruction	1/72 (1.4%)	1
Repro system/breast ds-Oth	1/72 (1.4%)	1
Uterine hemorrhage	1/72 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis	1/72 (1.4%)	1
Atelectasis	9/72 (12.5%)	9
Cough	17/72 (23.6%)	19
Dyspnea	23/72 (31.9%)	30
Epistaxis	10/72 (13.9%)	10
Hiccups	1/72 (1.4%)	1
Hoarseness	2/72 (2.8%)	2
Hypoxia	2/72 (2.8%)	2
Laryngeal inflammation	1/72 (1.4%)	1
Pleural effusion	14/72 (19.4%)	15
Pneumonitis	4/72 (5.6%)	4
Postnasal drip	10/72 (13.9%)	10
Productive Cough	3/72 (4.2%)	3
Pulmonary hypertension	1/72 (1.4%)	1
Resp/thoracic/mediastinal ds	2/72 (2.8%)	3
Sinus disorder	3/72 (4.2%)	3
Sore throat	1/72 (1.4%)	1
Upper respiratory infection	3/72 (4.2%)	5
Voice alteration	1/72 (1.4%)	1
Wheezing	1/72 (1.4%)	2
Skin and subcutaneous tissue disorders
Alopecia	46/72 (63.9%)	58
Bruising	5/72 (6.9%)	5
Bullous Dermatitis	1/72 (1.4%)	1
Dry Skin	4/72 (5.6%)	5
Erythema Multiforme	3/72 (4.2%)	5
Erythroderma	1/72 (1.4%)	3
Hyperhidrosis	1/72 (1.4%)	1
Nail discoloration	4/72 (5.6%)	4
Nail Loss	4/72 (5.6%)	4
Neck Edema	1/72 (1.4%)	1
Periorbital edema	1/72 (1.4%)	1
Pruritus	12/72 (16.7%)	14
Rash acneiform	30/72 (41.7%)	36
Rash maculo-papular	11/72 (15.3%)	19
Scalp pain	1/72 (1.4%)	1
Skin hyperpigmentation	3/72 (4.2%)	3
Skin hypopigmentation	1/72 (1.4%)	1
Skin ulceration	2/72 (2.8%)	2
Skin/subq tissue ds-Other	9/72 (12.5%)	17
Vascular disorders
Hematoma	1/72 (1.4%)	1
Hypertension	2/72 (2.8%)	3
Hypotension	12/72 (16.7%)	19
Thromboembolic event	16/72 (22.2%)	17
Vasc disorders-Other, spec	3/72 (4.2%)	3

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.