NCT00711243

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

Completed Phase 1, PHASE2 Results posted Last updated 26 February 2019

What this trial tests

Phase 1, PHASE2 trial testing docetaxel in Gastric Cancer in 59 participants. Completed in 25 February 2011.

Timeline

20 April 2005

Primary endpoint
15 December 2008

25 February 2011

Quick facts

Lead sponsor	Northwestern University
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	59
Start date	20 April 2005
Primary completion	15 December 2008
Estimated completion	25 February 2011
Sites	1 location across United States

Drugs / interventions tested

• docetaxel (Docetaxel) — full drug profile →
• fluorouracil — full drug profile →
• oxaliplatin (Oxaliplatin) — full drug profile →

Conditions studied

• Gastric Cancer — all drugs for Gastric Cancer →
• Unspecified Adult Solid Tumor, Protocol Specific — all drugs for Unspecified Adult Solid Tumor, Protocol Specific →

Sponsor

Northwestern University

Who can join

Adults 18 to 120, any sex, with Gastric Cancer or Unspecified Adult Solid Tumor, Protocol Specific. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I) Primary · 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 f

Group	Value	95% CI
Phase I	50

Response Rate in Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction (Phase II) Primary · 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 su

Group	Value	95% CI
Phase II	73.2

Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil Secondary · 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 g

Fatigue

Group	Value	95% CI
Cohort 1a	0
Cohort 2a	0
Cohort 3a	0
Cohort 4a	0
Cohort 5a	2

Diarrhea

Group	Value	95% CI
Cohort 1a	0
Cohort 2a	0
Cohort 3a	0
Cohort 4a	0
Cohort 5a	2

Toxicity Profile Secondary · 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

Neutropenia

Group	Value	95% CI
Phase II	23

Leukopenia

Group	Value	95% CI
Phase II	31

Lymphopenia

Group	Value	95% CI
Phase II	15

Anemia

Group	Value	95% CI
Phase II	30

Thrombocytopenia

Group	Value	95% CI
Phase II	13

Fatigue

Group	Value	95% CI
Phase II	36

Vomiting

Group	Value	95% CI
Phase II	22

Dehydration

Group	Value	95% CI
Phase II	5

Median Overall Survival (OS) Secondary · From first day of treatment until death from any cause measured, assessed up to 4 years

Median Overall Survival (OS)

Group	Value	95% CI
Phase II	10.3	8.1 – 15.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected over a 4 year period across the study.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1a

Serious: 0/3 (0%)

Deaths: 3/3

Cohort 2a

Serious: 0/3 (0%)

Deaths: 3/3

Cohort 3a

Serious: 1/3 (33%)

Deaths: 3/3

Cohort 4a

Serious: 0/3 (0%)

Deaths: 3/3

Cohort 5a

Serious: 2/3 (67%)

Deaths: 3/3

Phase II

Serious: 11/43 (26%)

Deaths: 41/43

Serious adverse events (16 terms)

Reaction	System	Cohort 1a	Cohort 2a	Cohort 3a	Cohort 4a	Cohort 5a	Phase II
Nausea and vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—	—
GI bleed	Gastrointestinal disorders	—	—	—	—	—	—
Death	Social circumstances	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—
Febrile neutropenia	Infections and infestations	—	—	—	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Speech impairment	Nervous system disorders	—	—	—	—	—	—
Rectal bleeding	Renal and urinary disorders	—	—	—	—	—	—
Brain metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pleural effusions	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—	—	—
Death	General disorders	—	—	—	—	—	—

Other adverse events (44 terms — click to expand)

Reaction	System	Cohort 1a	Cohort 2a	Cohort 3a	Cohort 4a	Cohort 5a	Phase II
Fatigue	General disorders	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Sensory neuropathy	Nervous system disorders	—	—	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Mucositis	Gastrointestinal disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Anorexia	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Transaminitis	Metabolism and nutrition disorders	—	—	—	—	—	—
Weight loss	General disorders	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Skin	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Altered taste	Gastrointestinal disorders	—	—	—	—	—	—
Shortness of breath	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Dehydration	Gastrointestinal disorders	—	—	—	—	—	—
Pain	General disorders	—	—	—	—	—	—
Hemorrhage	General disorders	—	—	—	—	—	—
Infection	Infections and infestations	—	—	—	—	—	—
Allergy	Immune system disorders	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Albumin, serum low	Metabolism and nutrition disorders	—	—	—	—	—	—
Motor Neuropathy	Nervous system disorders	—	—	—	—	—	—
Nail changes	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Edema	Blood and lymphatic system disorders	—	—	—	—	—	—
GI distention	Gastrointestinal disorders	—	—	—	—	—	—
Hypotension	Cardiac disorders	—	—	—	—	—	—
Alkaline phosphatase	Metabolism and nutrition disorders	—	—	—	—	—	—
Creatinine, Serum high	Metabolism and nutrition disorders	—	—	—	—	—	—
Auditory	Ear and labyrinth disorders	—	—	—	—	—	—
Insomnia	General disorders	—	—	—	—	—	—
Weight loss	General disorders	—	—	—	—	—	—
Nose bleed	General disorders	—	—	—	—	—	—
Hypoglycemia	Metabolism and nutrition disorders	—	—	—	—	—	—

Most-reported serious reactions: Nausea and vomiting, Acute myocardial infarction, GI bleed, Death, Diarrhea, Abdominal pain, Fever, Febrile neutropenia.

Data from ClinicalTrials.gov NCT00711243 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Trial watch: Chemotherapy with immunogenic cell death inducers.
   Vacchelli E, Galluzzi L, Fridman WH, Galon J, et al · · 2012 · cited 98× · PMID 22720239 · DOI 10.4161/onci.1.2.19026
2. Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long-Term Follow-Up.
   Rosenberg AJ, Rademaker A, Hochster HS, Ryan T, et al · · 2019 · cited 17× · PMID 31138725 · DOI 10.1634/theoncologist.2019-0330