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

NCT00711243 | Completed Phase 1 Results DMC

• 6 other identifiers: NU 04I2P30CA060553NU-0412SANOFI - AVENTIS-NU0412NU-948-006STU00006778
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; adenocarcinoma of the stomach; stage III gastric cancer; stage IV gastric cancer

Outcome Measures

Primary Outcomes (2)

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

  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

  After completion of 1 cycle of therapy (1 cycle = 14 days)

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

  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.

  After 4 cycles of therapy (1 cycle = 14 days)

Secondary Outcomes (5)

• Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil

  After 1 cycle of therapy (1 cycle = 14 days)

• 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

• 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

• 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

• 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

Study Arms (5)

Cohort 1a

EXPERIMENTAL

Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin

Cohort 2a

EXPERIMENTAL

Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin

Cohort 3a

EXPERIMENTAL

Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin

Cohort 4a

EXPERIMENTAL

Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin

Cohort 5a

EXPERIMENTAL

Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2

Drug: docetaxel; Drug: fluorouracil; Drug: oxaliplatin

Interventions

docetaxel DRUG

Docetaxel at the dose indicated by the patient cohort, administered intravenously in 5% dextrose over 1 hour on day 1 of each cycle.

Cohort 1a; Cohort 2a; Cohort 3a; Cohort 4a; Cohort 5a

fluorouracil DRUG

Intravenous infusion at 85 mg/m2 continuously over 46 hours beginning each cycle after docetaxel administration.

Cohort 1a; Cohort 2a; Cohort 3a; Cohort 4a; Cohort 5a

oxaliplatin DRUG

Oxaliplatin 2.4 gm/m2 administered intravenously in 5% dextrose over 2 hours each cycle beginning immediately following docetaxel

Cohort 1a; Cohort 2a; Cohort 3a; Cohort 4a; Cohort 5a

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Related Publications (1)

• Rosenberg AJ, Rademaker A, Hochster HS, Ryan T, Hensing T, Shankaran V, Baddi L, Mahalingam D, Mulcahy MF, Benson AB 3rd. Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long-Term Follow-Up. Oncologist. 2019 Aug;24(8):1039-e642. doi: 10.1634/theoncologist.2019-0330. Epub 2019 May 28.

  PMID: 31138725 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Docetaxel; Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes

Results Point of Contact

• Title: Mary Mulcahy (MD)
• Organization: Northwestern University

Mary.Mulcahy@nm.org

312.695.6182

Study Officials

• Mary Mulcahy, MD

  Robert H. Lurie Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2008
• First Posted: July 8, 2008
• Study Start: April 20, 2005
• Primary Completion: December 15, 2008
• Study Completion: February 25, 2011
• Last Updated: February 26, 2019
• Results First Posted: October 26, 2018

Record last verified: 2018-10

Locations

US (1)