Docetaxel, Oxaliplatin, and Fluorouracil in Treating Patients With Metastatic or Unresectable Stomach Cancer, Gastroesophageal Junction Cancer, or Other Solid Tumor

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00711243
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 59
• Location: 1
• Arms: 5
• Actual Duration (Months): 70.2
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given with oxaliplatin and fluorouracil and to see how well they work in treating patients with metastatic or unresectable stomach cancer, gastroesophageal junction cancer, or other solid tumor.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer; Unspecified Adult Solid Tumor, Protocol Specific	Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• To establish the maximum tolerated dose of docetaxel when administered with oxaliplatin and fluorouracil in patients with metastatic or unresectable solid tumors. (Phase I)

• To determine the response rate in patients with metastatic or unresectable adenocarcinoma of the stomach or gastroesophageal junction treated with this regimen. (Phase II)

Secondary

• To determine the dose limiting toxicity of this regimen in these patients.

• To evaluate the frequency of CYP3A4, CYP3A5, and MDR polymorphisms and their impact on toxicity of docetaxel.

• To evaluate the frequency of XRCC1 and ERCC2 polymorphisms and their impact on the toxicity of oxaliplatin.

• To evaluate the frequency of DPD and TSER polymorphisms and their impact on the toxicity of fluorouracil.

• To characterize the toxicity profile of this regimen in these patients.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for at least 2 courses in the absence of disease progression, symptomatic tumor progression, or unacceptable toxicity.

Patients undergo blood sample collection periodically for pharmacokinetic and pharmacogenomic correlative studies. Plasma concentrations of docetaxel are analyzed by reverse-phase high performance liquid chromatography and tandem mass spectrometry. Polymorphisms in CYP3A4/5, MDR, and other genes are analyzed by PCR.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 73 patients (30 for phase I and 43 for phase II) will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil
• Actual Study Start Date: Apr 20, 2005
• Actual Primary Completion Date: Dec 15, 2008
• Actual Study Completion Date: Feb 25, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1a Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2	Drug: docetaxel; Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.; Drug: fluorouracil; Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.; Drug: oxaliplatin; Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 2a Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2	Drug: docetaxel; Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.; Drug: fluorouracil; Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.; Drug: oxaliplatin; Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 3a Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2	Drug: docetaxel; Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.; Drug: fluorouracil; Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.; Drug: oxaliplatin; Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 4a Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2	Drug: docetaxel; Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.; Drug: fluorouracil; Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.; Drug: oxaliplatin; Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Experimental: Cohort 5a Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2	Drug: docetaxel; Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.; Drug: fluorouracil; Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.; Drug: oxaliplatin; Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I) [After completion of 1 cycle of therapy (1 cycle = 14 days)]

   The MTD will be determined using a 3+3 dose escalating design. There will be 5 dose cohorts: Cohort 1a 25mg/m2 Cohort 2a 30mg/m2 Cohort 3a 40 mg/m2 Cohort 4a 50 mg/m2 Cohort 5a 60 mg/m2 3 patients will be enrolled at dose of 25mg/m2 docetaxel. If no dose limiting toxicities (DLTs) are seen then dose will be escalated to next cohort and 3 patients will be treated at that dose level. If a DLT is seen at any dose, then 3 more patients will be enrolled at that dose level. If 1 patient out of 6, experience a DLT then MTD will be determined to be at this dose level. If 2 or more DLTs are seen in first 3 patients at that dose, then MTD will be one dose lower to the level where the DLTs were experienced. Dose of docetaxel will be escalated by use of cohorts until the MTD for phase II is determined. DLTs were defined using the National Cancer Institute Common Toxicity Criteria Version 3.0

2. Response Rate in Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction (Phase II) [After 4 cycles of therapy (1 cycle = 14 days)]

   Overall Response Rate (ORR) is defined as Complete Response (CR) plus Partial Response (PR) and will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan. Complete Response (CR) - Disappearance of all target lesions. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease, neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study. Progressive Disease - <=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.

Secondary Outcome Measures

1. Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil [After 1 cycle of therapy (1 cycle = 14 days)]

   Dose limiting toxicities (DLT) will be graded according to National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) except for neurosensory. The occurrence of any of the following during the 1st cycle, seen in more than one patient, will constitute a DLT. Grade 3 non-hematologic toxicity(except alopecia) Grade 4 thrombocytopenia, not recovered to platelet count of >75,000/ul by day 15. Grade 4 neutropenia, not recovered to count of >1,500/ul by day 15. Grade 4 neutropenia with fever or infection. Grade 2 neurologic-sensory toxicity not recovered to grade 1 or better by day 15

2. Frequency of CYP3A4, CYP3A5, and MDR Polymorphisms and Their Impact on Docetaxel Toxicity [Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle]

3. Frequency of XRCC1 and ERCC2 Polymorphisms and Their Impact on Oxaliplatin Toxicity [Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle]

4. Frequency of DPD and TSER Polymorphisms and Their Impact on Fluorouracil Toxicity [Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle]

5. Toxicity Profile [Day 1 of each cycle of therapy with 1 cycle =14 days until disease progression for up to a maximum of 34 cycles and 30 days after last treatment]

   Toxicity data will be collected on day 1 of every 14 day cycle during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events (AE) version 3.0 (CTCAE v3.0). For patients that experience multiple grades of the same AE that is determined to be at least possibly related to at least one study drug, only highest grade will be collected. In general AEs will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or surgically unresectable solid tumor meeting 1 of the following criteria:

• Any solid tumor (Phase I)

• Adenocarcinoma of the stomach or gastroesophageal junction (Phase II)

• Unidimensionally measurable disease by CT scan or MRI

• No uncontrolled brain metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 8.0 g/dL

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Total bilirubin normal

• Meets 1 of the following criteria:

• Alkaline phosphatase (AP) normal AND AST or ALT ≤ 5 times ULN

• AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN

• AP ≤ 5 times ULN AND AST or ALT normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy

• No preexisting neuropathy

• No concurrent uncontrolled illness or other condition that would preclude study compliance

• No history of severe hypersensitivity reaction to docetaxel or to other drugs formulated with polysorbate 80

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy

• More than 4 weeks since prior therapy (Phase I)

• No prior oxaliplatin or taxanes (Phase I)

• More than 4 weeks since prior radiotherapy (Phase I)

• No more than two prior therapies for metastatic disease (Phase I)

• No prior therapy for metastatic disease (Phase II)

• At least 6 months since prior adjuvant therapy (given prior to the occurrence of metastatic disease) (Phase II)

• Prior fluorouracil and concurrent radiotherapy for palliation of the primary tumor allowed provided metastatic disease is present outside the radiotherapy field (Phase II)

• No prior radiotherapy to ≥ 30% of bone marrow

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mary Mulcahy, MD, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00711243
• Other Study ID Numbers: NU 04I2; P30CA060553; NU-0412; SANOFI - AVENTIS-NU0412; NU-948-006; STU00006778
• First Posted: Jul 8, 2008
• Last Update Posted: Feb 26, 2019
• Last Verified: Oct 1, 2018

• Keywords provided by Northwestern University: unspecified adult solid tumor, protocol specific; adenocarcinoma of the stomach; stage III gastric cancer; stage IV gastric cancer
• Additional relevant MeSH terms: Stomach Neoplasms; Docetaxel; Fluorouracil; Oxaliplatin

Study Results

Participant Flow

Recruitment Details	The study opened for accrual on March 3, 2005 and the first patient was enrolled April 20 2005. Accrual goal of approximately 50 for the phase I and phase II portion. Accrual for phase I was suspended on February 13 2006 reopened with phase II accrual on February 16, 2006. The study was closed permanently on July 23, 2008.
Pre-assignment Detail	Phase I was opened to all solid tumor cancers and phase II was opened to stomach/gastro-esophageal junction cancer only.

Arm/Group Title	Cohort 1a	Cohort 2a	Cohort 3a	Cohort 4a	Cohort 5a	Phase II
Arm/Group Description	Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Period Title: Registed and Started Treatment
STARTED	3	3	3	3	3	44
Registered to Study	3	3	3	3	3	44
Started Treatment	3	3	3	3	3	43
COMPLETED	3	3	3	3	3	43
NOT COMPLETED	0	0	0	0	0	1
Period Title: Registed and Started Treatment
STARTED	3	3	3	3	3	43
COMPLETED	3	3	3	2	3	41
NOT COMPLETED	0	0	0	1	0	2
Period Title: Registed and Started Treatment
STARTED	3	3	3	2	3	41
COMPLETED	2	1	3	2	2	37
NOT COMPLETED	1	2	0	0	1	4
Period Title: Registed and Started Treatment
STARTED	3	3	3	3	3	39
COMPLETED	3	3	3	3	3	37
NOT COMPLETED	0	0	0	0	0	2

Baseline Characteristics

Arm/Group Title	Cohort 1a	Cohort 2a	Cohort 3a	Cohort 4a	Cohort 5a	Phase II	Total
Arm/Group Description	Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Total of all reporting groups
Overall Participants	3	3	3	3	3	44	59
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	3 100%	1 33.3%	0 0%	1 33.3%	28 63.6%	35 59.3%
>=65 years	1 33.3%	0 0%	2 66.7%	3 100%	2 66.7%	16 36.4%	24 40.7%
Sex: Female, Male (Count of Participants)
Female	2 66.7%	1 33.3%	2 66.7%	1 33.3%	2 66.7%	14 31.8%	22 37.3%
Male	1 33.3%	2 66.7%	1 33.3%	2 66.7%	1 33.3%	30 68.2%	37 62.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 33.3%	0 0%	0 0%	0 0%	3 6.8%	4 6.8%
Not Hispanic or Latino	3 100%	2 66.7%	2 66.7%	3 100%	3 100%	36 81.8%	49 83.1%
Unknown or Not Reported	0 0%	0 0%	1 33.3%	0 0%	0 0%	5 11.4%	6 10.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	8 18.2%	8 13.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 33.3%	1 33.3%	0 0%	0 0%	0 0%	6 13.6%	8 13.6%
White	2 66.7%	2 66.7%	2 66.7%	3 100%	3 100%	30 68.2%	42 71.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 1.7%
Region of Enrollment (Count of Participants)
United States	3 100%	3 100%	3 100%	3 100%	3 100%	44 100%	59 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I)
Description	The MTD will be determined using a 3+3 dose escalating design. There will be 5 dose cohorts: Cohort 1a 25mg/m2 Cohort 2a 30mg/m2 Cohort 3a 40 mg/m2 Cohort 4a 50 mg/m2 Cohort 5a 60 mg/m2 3 patients will be enrolled at dose of 25mg/m2 docetaxel. If no dose limiting toxicities (DLTs) are seen then dose will be escalated to next cohort and 3 patients will be treated at that dose level. If a DLT is seen at any dose, then 3 more patients will be enrolled at that dose level. If 1 patient out of 6, experience a DLT then MTD will be determined to be at this dose level. If 2 or more DLTs are seen in first 3 patients at that dose, then MTD will be one dose lower to the level where the DLTs were experienced. Dose of docetaxel will be escalated by use of cohorts until the MTD for phase II is determined. DLTs were defined using the National Cancer Institute Common Toxicity Criteria Version 3.0
Time Frame	After completion of 1 cycle of therapy (1 cycle = 14 days)

Outcome Measure Data

Analysis Population Description

Dose of docetaxel was escalated up through 5 cohorts.

Arm/Group Title	Phase I
Arm/Group Description	Docetaxel + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. Dose for cohorts is as follows: Cohort 1a = Docetaxel 25mg/m2 Cohort 2a = Docetaxel 30mg/m2 Cohort 3a = Docetaxel 40mg/m2 Cohort 4a = Docetaxel 50mg/m2 Cohort 5a = Docetaxel 60mg/m2 fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	15
Number [mg/m2]	50

2. Primary Outcome

Title	Response Rate in Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction (Phase II)
Description	Overall Response Rate (ORR) is defined as Complete Response (CR) plus Partial Response (PR) and will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan. Complete Response (CR) - Disappearance of all target lesions. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease, neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study. Progressive Disease - <=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.
Time Frame	After 4 cycles of therapy (1 cycle = 14 days)

Outcome Measure Data

Analysis Population Description

One patient that was registered to phase II did not get treated on study and was therefore not evaluable. Two patients did not reach first response at 4 cycles and therefore were not evaluable.

Arm/Group Title	Phase II
Arm/Group Description	Docetaxel 50mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 Docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. Fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. Oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	41
Number [percentage of patients]	73.2

3. Secondary Outcome

Title	Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil
Description	Dose limiting toxicities (DLT) will be graded according to National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) except for neurosensory. The occurrence of any of the following during the 1st cycle, seen in more than one patient, will constitute a DLT. Grade 3 non-hematologic toxicity(except alopecia) Grade 4 thrombocytopenia, not recovered to platelet count of >75,000/ul by day 15. Grade 4 neutropenia, not recovered to count of >1,500/ul by day 15. Grade 4 neutropenia with fever or infection. Grade 2 neurologic-sensory toxicity not recovered to grade 1 or better by day 15
Time Frame	After 1 cycle of therapy (1 cycle = 14 days)

Outcome Measure Data

Analysis Population Description

15 patients enrolled in 5 dose escalating cohorts were monitored for DLTs in the phase I part of the study.

Arm/Group Title	Cohort 1a	Cohort 2a	Cohort 3a	Cohort 4a	Cohort 5a
Arm/Group Description	Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel	Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	3	3	3	3	3
Fatigue	0 0%	0 0%	0 0%	0 0%	2 66.7%
Diarrhea	0 0%	0 0%	0 0%	0 0%	2 66.7%

4. Secondary Outcome

Title	Frequency of CYP3A4, CYP3A5, and MDR Polymorphisms and Their Impact on Docetaxel Toxicity
Time Frame	Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Phase I and Phase II
Arm/Group Description	Docetaxel (between 25 mg/m2 and 60mg/m2) + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	0

5. Secondary Outcome

Title	Frequency of XRCC1 and ERCC2 Polymorphisms and Their Impact on Oxaliplatin Toxicity
Time Frame	Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Phase I and Phase II
Arm/Group Description	Docetaxel (between 25 mg/m2 and 60mg/m2) + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	0

6. Secondary Outcome

Title	Frequency of DPD and TSER Polymorphisms and Their Impact on Fluorouracil Toxicity
Time Frame	Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Phase I and Phase II
Arm/Group Description	Docetaxel (between 25 mg/m2 and 60mg/m2) + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	0

7. Secondary Outcome

Title	Toxicity Profile
Description	Toxicity data will be collected on day 1 of every 14 day cycle during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events (AE) version 3.0 (CTCAE v3.0). For patients that experience multiple grades of the same AE that is determined to be at least possibly related to at least one study drug, only highest grade will be collected. In general AEs will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time Frame	Day 1 of each cycle of therapy with 1 cycle =14 days until disease progression for up to a maximum of 34 cycles and 30 days after last treatment

Outcome Measure Data

Analysis Population Description

Data collected and analyzed for patients enrolled in the phase II of the study only.1 Patient did not receive treatment on study and was not evaluable. For each patient that experienced the toxicity, highest grade for that patient is recorded. Grades ranging between 1-5 were collected and are represented below.

Arm/Group Title	Phase II
Arm/Group Description	Docetaxel 50mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 Docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. Fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. Oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	43
Neutropenia	23 766.7%
Leukopenia	31 1033.3%
Lymphopenia	15 500%
Anemia	30 1000%
Thrombocytopenia	13 433.3%
Fatigue	36 1200%
Vomiting	22 733.3%
Dehydration	5 166.7%
Infection	4 133.3%
Nausea	31 1033.3%
Pain	5 166.7%
Allergy	4 133.3%
Transaminitis	7 233.3%
Rash	3 100%
Weight loss	6 200%
Anorexia	13 433.3%
Fever	4 133.3%
Hypertension	2 66.7%
Hyperglycemia	3 100%
Diarrhea	22 733.3%
Constipation	10 333.3%
Mucositis	14 466.7%
Neuro-sens	30 1000%
Neuro-motor	2 66.7%
Nail changes	2 66.7%
Alopecia	6 200%
Skin	6 200%
Hemorrhage	5 166.7%
Altered taste	6 200%
Edema	2 66.7%
Abdominal distension	2 66.7%
Shortness of breath	6 200%

8. Post-Hoc Outcome

Title	Median Overall Survival (OS)
Description	Median Overall Survival (OS)
Time Frame	From first day of treatment until death from any cause measured, assessed up to 4 years

Outcome Measure Data

Analysis Population Description

Patients enrolled in phase II portion of the study were evaluable for OS. One patient in phase II was registered to the study but did not receive treatment and was not evaluable for OS. Two patients did not have death dates and were censored for the last known time to be living.

Arm/Group Title	Phase II
Arm/Group Description	Docetaxel 50mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 Docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. Fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. Oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
Measure Participants	43
Median (95% Confidence Interval) [Months]	10.3

Adverse Events

Time Frame	Adverse events were collected over a 4 year period across the study.
Adverse Event Reporting Description	Adverse events were collected in systematic assessment every two weeks during patient visit. For each patient the highest grade of clinically significant adverse events were collected only.
Arm/Group Title	Cohort 1a		Cohort 2a		Cohort 3a		Cohort 4a		Cohort 5a		Phase II
Arm/Group Description	Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel		Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel		Docetaxel 40 mg/m2+ oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel		Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel		Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel		Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2 docetaxel: Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle. fluorouracil: Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration. oxaliplatin: Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel
All Cause Mortality
	Cohort 1a		Cohort 2a		Cohort 3a		Cohort 4a		Cohort 5a		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		41/43 (95.3%)
Serious Adverse Events
	Cohort 1a		Cohort 2a		Cohort 3a		Cohort 4a		Cohort 5a		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		2/3 (66.7%)		11/43 (25.6%)
Cardiac disorders
Acute myocardial infarction	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Gastrointestinal disorders
GI bleed	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Diarrhea	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Abdominal pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Nausea and vomiting	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/43 (4.7%)
General disorders
Fever	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Death	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Infections and infestations
Febrile neutropenia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/43 (2.3%)
Metabolism and nutrition disorders
Hypokalemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain metastasis	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/43 (0%)
Nervous system disorders
Speech impairment	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/43 (0%)
Renal and urinary disorders
Rectal bleeding	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/43 (2.3%)
Pleural effusions	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Social circumstances
Death	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Vascular disorders
Deep vein thrombosis	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Cohort 1a		Cohort 2a		Cohort 3a		Cohort 4a		Cohort 5a		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		43/43 (100%)
Blood and lymphatic system disorders
Neutropenia	0/3 (0%)		1/3 (33.3%)		2/3 (66.7%)		2/3 (66.7%)		1/3 (33.3%)		23/43 (53.5%)
Leukopenia	0/3 (0%)		1/3 (33.3%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		31/43 (72.1%)
Lymphopenia	3/3 (100%)		1/3 (33.3%)		3/3 (100%)		1/3 (33.3%)		0/3 (0%)		15/43 (34.9%)
Anemia	3/3 (100%)		1/3 (33.3%)		2/3 (66.7%)		1/3 (33.3%)		2/3 (66.7%)		30/43 (69.8%)
Thrombocytopenia	2/3 (66.7%)		2/3 (66.7%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		13/43 (30.2%)
Edema	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		2/43 (4.7%)
Cardiac disorders
Hypotension	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/43 (4.7%)
Ear and labyrinth disorders
Auditory	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		2/3 (66.7%)		22/43 (51.2%)
Mucositis	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		14/43 (32.6%)
Vomiting	1/3 (33.3%)		0/3 (0%)		3/3 (100%)		2/3 (66.7%)		1/3 (33.3%)		22/43 (51.2%)
Dehydration	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		5/43 (11.6%)
Nausea	2/3 (66.7%)		1/3 (33.3%)		3/3 (100%)		3/3 (100%)		1/3 (33.3%)		31/43 (72.1%)
Anorexia	0/3 (0%)		2/3 (66.7%)		3/3 (100%)		1/3 (33.3%)		0/3 (0%)		13/43 (30.2%)
Constipation	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		10/43 (23.3%)
Altered taste	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		2/3 (66.7%)		6/43 (14%)
GI distention	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/43 (4.7%)
GI Bleed	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
General disorders
Fatigue	2/3 (66.7%)		2/3 (66.7%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		36/43 (83.7%)
Pain	2/3 (66.7%)		1/3 (33.3%)		1/3 (33.3%)		2/3 (66.7%)		2/3 (66.7%)		5/43 (11.6%)
Weight loss	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		6/43 (14%)
Fever	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		4/43 (9.3%)
Hemorrhage	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		5/43 (11.6%)
Insomnia	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Weight loss	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Nose bleed	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Immune system disorders
Allergy	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		4/43 (9.3%)
Infections and infestations
Infection	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		4/43 (9.3%)
Metabolism and nutrition disorders
Transaminitis	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		7/43 (16.3%)
Hyperglycemia	3/3 (100%)		1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		3/43 (7%)
Alkaline phosphatase	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Albumin, serum low	2/3 (66.7%)		1/3 (33.3%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		1/43 (2.3%)
Creatinine, Serum high	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Hypoglycemia	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Nervous system disorders
Sensory neuropathy	1/3 (33.3%)		2/3 (66.7%)		2/3 (66.7%)		2/3 (66.7%)		2/3 (66.7%)		30/43 (69.8%)
Motor Neuropathy	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		2/43 (4.7%)
Speech	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/43 (0%)
Psychiatric disorders
Depression	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Anxiety	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Skin	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		6/43 (14%)
Shortness of breath	0/3 (0%)		1/3 (33.3%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		6/43 (14%)
Skin and subcutaneous tissue disorders
Rash	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		3/43 (7%)
Nail changes	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		2/43 (4.7%)
Alopecia	1/3 (33.3%)		0/3 (0%)		2/3 (66.7%)		1/3 (33.3%)		2/3 (66.7%)		6/43 (14%)

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.