Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer

• Sponsor: Hoosier Cancer Research Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT02375672
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 30
• Locations: 3
• Arm: 1
• Actual Duration (Months): 64.4
• Patients Per Site: 10
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a multi-institutional, single arm, open-label, phase II study, including a safety run-in cohort. No randomization or blinding involved.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Pembrolizumab; Drug: mFOLFOX6	Phase 2

Detailed Description

OUTLINE: This is a multi-center study.

INVESTIGATIONAL TREATMENT:

mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

• Oxaliplatin 85 mg/m2 IV with

• Leucovorin 400 mg/m2 IV followed by

• 5FU 400 mg/m2 bolus and then 2400 mg/m2 via continuous infusion

Pembrolizumab (MK-3475) IV over 30 minutes every 3 weeks

SAFETY RUN-IN COHORT:

The safety run-in cohort will include 6 subjects treated with 200 mg (fixed) IV infusion of pembrolizumab (MK-3475) every 3 weeks plus standard-dose mFOLFOX6 given every 2 weeks. These first 6 subjects will be followed for 4 weeks for dose limiting toxicities (DLT) before enrolling an additional 24 patients. If a DLT is observed in no more than 1 of 6 subjects, the trial will continue with enrolling subjects to the remainder of the phase II portion of the study. Otherwise, 6 additional subjects will be enrolled at dose level -1. If no more than one DLT is observed, then phase II will enroll subjects at dose level -1 for the total expected number of accrual.

Disease evaluation every 8 weeks or after every 2 cycles

Demonstrate adequate organ function as defined by the following laboratory values at study entry. All screening labs should be performed within 14 days prior to registration for protocol therapy.

Hematopoietic:

• Hemoglobin ≥ 9 g/dL (transfusions are acceptable)

• Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L

• Platelets ≥ 100 × 10^9/L

Renal:

• Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or measured or calculated creatinine clearance (estimated by Cockcroft-Gault formula below or measured) ≥ 50 mL/min

Hepatic:

• Serum total bilirubin ≤ 1.5 × ULN

• Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 3 × ULN, unless evidence of liver metastases, then AST/ALT ≤ 5 x ULN

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Single Arm, Phase II Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer: HCRN GI14-186
• Actual Study Start Date: May 28, 2015
• Actual Primary Completion Date: Oct 8, 2020
• Actual Study Completion Date: Oct 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab (MK-3475) + mFOLFOX6 Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)	Drug: Pembrolizumab; Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks; Other Names: MK-3475 ; Drug: mFOLFOX6; mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion

Outcome Measures

Primary Outcome Measures

1. Median Progression Free Survival (mPFS) [From time of registration to the time of documented progression per RECIST 1.1 or subject death (estimate 14 months)]

   Determine if pembrolizumab (MK-3475) in combination with chemotherapy improves median progression free survival (mPFS) compared to historical standards. Response Criteria - Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Secondary Outcome Measures

1. Disease Assessment for Objective Response Rate (ORR) [Begin C1D1 and every 8 weeks thereafter (up to 24 months)]

   To determine the number of patients who achieve complete response and partial response per irRC criteria.

2. Disease Assessment for Disease Control Rate [Begin C1D1 and every 8 weeks thereafter (up to 24 months) per RECIST 1.1 criteria]

   Disease control rate (DCR), defined as the sum of subjects with complete response, partial response and stable disease per RECIST 1.1 criteria.

3. Overall Survival (OS) [Subject should be followed from time of registration till the time of subject death up to a maximum 35.5 months]

   Overall Survival (OS) reported as number of subject alive at a median followup time of 19.9 months.

4. Number of Patients With Grade 3 or Higher Treatment Related Adverse Event [Begin C1D1 and very 2 weeks (Day 1) for up to 24 months]

   To assess safety and tolerability of mFOLFOX6 and pembrolizumab (MK-3475) combination chemotherapy in patients with advanced colorectal cancer per CTCAE v4.0. Events are considered related if they assessed possible, probable or definite with study drug.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Be willing and able to provide written informed consent for the trial and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

• Be ≥ 18 years of age on day of signing informed consent.

• Have a performance status of 0 or 1 on the ECOG Performance Scale within 14 days prior to registration.

• Have histological or cytological evidence of colorectal adenocarcinoma with confirmation of metastatic disease either by pathologic or radiologic findings.

• Have identified tissue from an archival tissue sample (preferably from a metastasis, but sample from primary tumor allowable) or newly obtained core or excisional biopsy of a tumor lesion.

• Have had no prior systemic therapy for advanced or metastatic disease. Prior adjuvant therapy should have been completed at least 9 months from documentation of metastatic disease. Prior palliative radiotherapy allowed if toxicities resolved to grade 1 or baseline.

• Have measurable disease according to RECIST v1.1 obtained by imaging within 28 days prior to registration.

• Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 14 days prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Subjects of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) are those who meet the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; OR has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication

Exclusion Criteria:

• Has clearly resectable colon cancer liver metastases (CCLM), for example oligometastatic disease involving only one lobe of the liver. Subjects with suspected resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to document the incurable nature of their disease.

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of registration. Subjects are not permitted to participate in another investigational drug study while being treated on this protocol.

• Is unable to receive a port or peripherally inserted central catheter (PICC).

• Has a diagnosis of immunodeficiency or is receiving chronic steroid therapy of prednisone ≥ 10 mg daily or any equivalent dose of corticosteroids.

• Has previously undergone organ or bone marrow transplantation and is on immunosuppressive therapy

• Has had major surgery or significant traumatic injury within 4 weeks of study registration. Subjects must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. A diagnostic or research biopsy does not exclude subjects from enrollment. Placement of a vascular access device such as a Port-A-Cath is not considered major surgery

• Has baseline peripheral neuropathy/paresthesia grade ≥ 1.

• Has a known additional malignancy within the past 3 years. Exceptions include treated localized basal cell or squamous cell carcinoma of the skin, in situ cervical or vulvar carcinoma that has undergone potentially curative therapy, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade prostate cancer (Gleason sore 6). Any cancer curatively treated > 3 years prior to registration with no clinical evidence of recurrence is permitted

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to trial registration and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial registration.

• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions to the rule: subjects with vitiligo; subjects with resolved childhood asthma/atopy; subjects that require intermittent use of bronchodilators or local steroid injections; subjects with hypothyroidism stable on hormone replacement or patients with Sjögren's syndrome

• Has a history of pneumonitis that required steroids or current pneumonitis.

• Has known history of active tuberculosis.

• Has an active infection requiring systemic therapy (≥ grade 2) for more than 3 days within 1 week of enrollment.

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of pembrolizumab (MK-3475).

• Has known hypersensitivity to fluorouracil (5FU), oxaliplatin, or other platinum agents.

• Known hypersensitivity to pembrolizumab or any of its excipients.

• Has known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency (testing not required)

• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

• Has known active Hepatitis B unless subject has been on antiviral agents for at least 2 months (baseline testing not required)

• Has a known history of Human Immunodeficiency Virus (HIV) or Hepatitis C (baseline testing is not required).

• Has received a live vaccine within 30 days prior to trial registration.

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator.

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

• Has any other psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Those conditions should be discussed with the subject before registration in the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University: Winship Cancer Institute	Atlanta	Georgia	United States	30322
2	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
3	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Hoosier Cancer Research Network
• Merck Sharp & Dohme LLC

Investigators

• Study Chair: Safi Shahda, M.D., Hoosier Cancer Research Network

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 29, 2019

More Information

Additional Information:

• Hoosier Cancer Research Network Website

Publications

None provided.

• Responsible Party: Kathy Miller, MD, Principal Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT02375672
• Other Study ID Numbers: HCRN GI14-186
• First Posted: Mar 2, 2015
• Last Update Posted: Feb 16, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kathy Miller, MD, Principal Investigator, Hoosier Cancer Research Network: Pembrolizumab; MK-3475
• Additional relevant MeSH terms: Colorectal Neoplasms; Pembrolizumab

Study Results

Participant Flow

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Period Title: Overall Study
STARTED	30
COMPLETED	10
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Participants	30
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	47.5
Sex: Female, Male (Count of Participants)
Female	11 36.7%
Male	19 63.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	29 96.7%
Unknown or Not Reported	1 3.3%
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	4 13.3%
White	26 86.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%
ECOG Performance Status (Count of Participants)
0	21 70%
1	9 30%
Stage at Presentation (Count of Participants)
I	1 3.3%
II A	2 6.7%
II B	0 0%
III A	0 0%
III B	2 6.7%
III C	3 10%
IV	22 73.3%
Sites of Metastasis (participants) [Number]
Liver	22 73.3%
Lung	7 23.3%
Lymph Node	5 16.7%
Bone	2 6.7%
Ileum	3 10%
Peritoneum	3 10%
Other	5 16.7%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival (mPFS)
Description	Determine if pembrolizumab (MK-3475) in combination with chemotherapy improves median progression free survival (mPFS) compared to historical standards. Response Criteria - Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Time Frame	From time of registration to the time of documented progression per RECIST 1.1 or subject death (estimate 14 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Measure Participants	30
Median (80% Confidence Interval) [months]	8.8

2. Secondary Outcome

Title	Disease Assessment for Objective Response Rate (ORR)
Description	To determine the number of patients who achieve complete response and partial response per irRC criteria.
Time Frame	Begin C1D1 and every 8 weeks thereafter (up to 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Measure Participants	30
Count of Participants [Participants]	17 56.7%

3. Secondary Outcome

Title	Disease Assessment for Disease Control Rate
Description	Disease control rate (DCR), defined as the sum of subjects with complete response, partial response and stable disease per RECIST 1.1 criteria.
Time Frame	Begin C1D1 and every 8 weeks thereafter (up to 24 months) per RECIST 1.1 criteria

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Measure Participants	30
Count of Participants [Participants]	30 100%

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) reported as number of subject alive at a median followup time of 19.9 months.
Time Frame	Subject should be followed from time of registration till the time of subject death up to a maximum 35.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Measure Participants	30
Alive	20 66.7%
Expired	10 33.3%

5. Secondary Outcome

Title	Number of Patients With Grade 3 or Higher Treatment Related Adverse Event
Description	To assess safety and tolerability of mFOLFOX6 and pembrolizumab (MK-3475) combination chemotherapy in patients with advanced colorectal cancer per CTCAE v4.0. Events are considered related if they assessed possible, probable or definite with study drug.
Time Frame	Begin C1D1 and very 2 weeks (Day 1) for up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Measure Participants	30
Count of Participants [Participants]	15 50%

Adverse Events

Time Frame	Adverse events (AEs) was reported from the time of consent and until 30 days after last dose of study drug up to a maximum 108 weeks.
Adverse Event Reporting Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) v4 were utilized for AE reporting
Arm/Group Title	Pembrolizumab (MK-3475) + mFOLFOX6
Arm/Group Description	Following the safety run-in cohort: mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks) Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days) Oxaliplatin 85 mg/m^2 IV with Leucovorin 400 mg/m^2 IV followed by 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
All Cause Mortality
	Pembrolizumab (MK-3475) + mFOLFOX6
	Affected / at Risk (%)	# Events
Total	10/30 (33.3%)
Serious Adverse Events
	Pembrolizumab (MK-3475) + mFOLFOX6
	Affected / at Risk (%)	# Events
Total	7/30 (23.3%)
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA	3/30 (10%)	3
Endocrine disorders
ENDOCRINE DISORDERS	1/30 (3.3%)	1
Gastrointestinal disorders
COLITIS	1/30 (3.3%)	1
DIARRHEA	1/30 (3.3%)	1
GASTROINTESTINAL DISORDERS	1/30 (3.3%)	1
NAUSEA	1/30 (3.3%)	1
VOMITING	1/30 (3.3%)	1
General disorders
FEVER	1/30 (3.3%)	1
Immune system disorders
ANAPHYLAXIS	1/30 (3.3%)	1
Vascular disorders
THROMBOEMBOLIC EVENT	1/30 (3.3%)	2
Other (Not Including Serious) Adverse Events
	Pembrolizumab (MK-3475) + mFOLFOX6
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
ANEMIA	5/30 (16.7%)	7
BLOOD AND LYMPHATIC SYSTEM DISORDERS	1/30 (3.3%)	1
FEBRILE NEUTROPENIA	1/30 (3.3%)	1
Endocrine disorders
ADRENAL INSUFFICIENCY	1/30 (3.3%)	1
HYPERTHYROIDISM	1/30 (3.3%)	1
HYPOTHYROIDISM	3/30 (10%)	4
Eye disorders
CONJUNCTIVITIS	1/30 (3.3%)	2
EYE DISORDERS	1/30 (3.3%)	1
EYE PAIN	1/30 (3.3%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	10/30 (33.3%)	16
ASCITES	1/30 (3.3%)	3
BLOATING	2/30 (6.7%)	2
CONSTIPATION	10/30 (33.3%)	15
DIARRHEA	14/30 (46.7%)	31
DRY MOUTH	2/30 (6.7%)	2
DYSPEPSIA	5/30 (16.7%)	5
FECAL INCONTINENCE	1/30 (3.3%)	2
GASTROINTESTINAL DISORDERS	3/30 (10%)	3
HEMORRHOIDAL HEMORRHAGE	1/30 (3.3%)	1
LIP PAIN	1/30 (3.3%)	1
MUCOSITIS ORAL	10/30 (33.3%)	15
NAUSEA	22/30 (73.3%)	37
ORAL PAIN	1/30 (3.3%)	1
RECTAL HEMORRHAGE	5/30 (16.7%)	10
RECTAL PAIN	2/30 (6.7%)	2
VOMITING	9/30 (30%)	13
General disorders
CHILLS	4/30 (13.3%)	6
EDEMA LIMBS	3/30 (10%)	4
FACIAL PAIN	1/30 (3.3%)	1
FATIGUE	18/30 (60%)	63
FEVER	5/30 (16.7%)	8
GAIT DISTURBANCE	1/30 (3.3%)	1
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	3/30 (10%)	3
INFUSION RELATED REACTION	2/30 (6.7%)	3
PAIN	1/30 (3.3%)	1
Immune system disorders
ALLERGIC REACTION	1/30 (3.3%)	1
Infections and infestations
PAPULOPUSTULAR RASH	2/30 (6.7%)	2
SINUSITIS	1/30 (3.3%)	1
UPPER RESPIRATORY INFECTION	2/30 (6.7%)	2
URINARY TRACT INFECTION	1/30 (3.3%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	8/30 (26.7%)	13
ALKALINE PHOSPHATASE INCREASED	5/30 (16.7%)	6
ASPARTATE AMINOTRANSFERASE INCREASED	7/30 (23.3%)	12
BLOOD BILIRUBIN INCREASED	6/30 (20%)	11
LYMPHOCYTE COUNT DECREASED	3/30 (10%)	11
NEUTROPHIL COUNT DECREASED	10/30 (33.3%)	21
PLATELET COUNT DECREASED	8/30 (26.7%)	26
WEIGHT GAIN	2/30 (6.7%)	2
WEIGHT LOSS	5/30 (16.7%)	5
WHITE BLOOD CELL DECREASED	5/30 (16.7%)	18
Metabolism and nutrition disorders
ANOREXIA	8/30 (26.7%)	16
DEHYDRATION	1/30 (3.3%)	1
HYPERCALCEMIA	2/30 (6.7%)	2
HYPERGLYCEMIA	8/30 (26.7%)	35
HYPOALBUMINEMIA	3/30 (10%)	4
HYPOGLYCEMIA	1/30 (3.3%)	1
HYPOKALEMIA	4/30 (13.3%)	4
Musculoskeletal and connective tissue disorders
ARTHRITIS	1/30 (3.3%)	1
BACK PAIN	3/30 (10%)	4
BONE PAIN	1/30 (3.3%)	1
BUTTOCK PAIN	1/30 (3.3%)	1
GENERALIZED MUSCLE WEAKNESS	1/30 (3.3%)	1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER	3/30 (10%)	4
NECK PAIN	1/30 (3.3%)	1
PAIN IN EXTREMITY	2/30 (6.7%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)	1/30 (3.3%)	1
Nervous system disorders
DYSESTHESIA	2/30 (6.7%)	3
DYSGEUSIA	6/30 (20%)	7
HEADACHE	6/30 (20%)	8
NERVOUS SYSTEM DISORDERS	6/30 (20%)	15
PARESTHESIA	4/30 (13.3%)	4
PERIPHERAL MOTOR NEUROPATHY	1/30 (3.3%)	1
PERIPHERAL SENSORY NEUROPATHY	19/30 (63.3%)	68
SINUS PAIN	1/30 (3.3%)	1
SOMNOLENCE	1/30 (3.3%)	1
SYNCOPE	1/30 (3.3%)	1
Psychiatric disorders
ANXIETY	2/30 (6.7%)	2
DEPRESSION	3/30 (10%)	4
HALLUCINATIONS	1/30 (3.3%)	1
INSOMNIA	2/30 (6.7%)	4
Renal and urinary disorders
HEMATURIA	1/30 (3.3%)	1
RENAL AND URINARY DISORDERS	1/30 (3.3%)	1
Reproductive system and breast disorders
ERECTILE DYSFUNCTION	1/30 (3.3%)	1
PELVIC PAIN	1/30 (3.3%)	1
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS	2/30 (6.7%)	2
COUGH	3/30 (10%)	8
DYSPNEA	3/30 (10%)	3
EPISTAXIS	1/30 (3.3%)	1
NASAL CONGESTION	1/30 (3.3%)	2
PNEUMONITIS	2/30 (6.7%)	2
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS	1/30 (3.3%)	1
SINUS DISORDER	1/30 (3.3%)	1
SORE THROAT	3/30 (10%)	3
Skin and subcutaneous tissue disorders
ALOPECIA	3/30 (10%)	3
DRY SKIN	2/30 (6.7%)	2
HYPERHIDROSIS	1/30 (3.3%)	1
PRURITUS	3/30 (10%)	4
RASH ACNEIFORM	4/30 (13.3%)	4
RASH MACULO-PAPULAR	4/30 (13.3%)	4
SKIN AND SUBCUTANEOUS TISSUE DISORDERS	3/30 (10%)	3
SKIN HYPERPIGMENTATION	1/30 (3.3%)	1
Vascular disorders
HYPERTENSION	3/30 (10%)	4
HYPOTENSION	1/30 (3.3%)	1

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.