Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01142388
First received: June 10, 2010
Last updated: August 5, 2014
Last verified: June 2014
  Purpose

This randomized phase II trial studies how well paclitaxel with or without cixutumumab works in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as cixutumumab, find tumor cells and help kill them. Giving paclitaxel with or without cixutumumab may kill more tumor cells.


Condition Intervention Phase
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Gastroesophageal Junction
Recurrent Esophageal Cancer
Squamous Cell Carcinoma of the Esophagus
Stage IV Esophageal Cancer
Biological: cixutumumab
Drug: paclitaxel
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Paclitaxel With or Without the Anti-IGF-IR mAb Cixutumumab (IMC-A12) as Second Line Treatment for Patients With Metastatic Esophageal or GE Junction Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival of paclitaxel plus cixutumumab versus paclitaxel alone as second-line therapy [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 12 months of follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival of paclitaxel plus cixutumumab versus paclitaxel alone [ Time Frame: From the date of entry on study, assessed up to 2 years ] [ Designated as safety issue: No ]
  • Response rate of paclitaxel plus cixutumumab versus paclitaxel alone evaluated using the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events of cixutumumab plus paclitaxel versus paclitaxel alone graded by Common Terminology Criteria for Adverse Events [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Pharmacodynamic biomarkers obtained from serum samples [ Time Frame: Up to course 5, day 1 ] [ Designated as safety issue: No ]
    Including but not limited to, IGF-I, IGF-II, IGFBP-2, and IGFBP-3.


Enrollment: 94
Study Start Date: September 2010
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (paclitaxel)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Arm II (cixutumumab, paclitaxel)
Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.
Biological: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone as second-line therapy in patients with metastatic esophagus or gastroesophageal (GE) junction cancer.

SECONDARY OBJECTIVES:

I. To evaluate the overall survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.

II. To evaluate the response rate of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.

III. To evaluate the toxicity of cixutumumab (IMC-A12) plus paclitaxel versus paclitaxel alone in this patient population.

IV. Exploratory analyses will assess potentially relevant cixutumumab (IMC-A12) pharmacodynamic biomarkers obtained from serum samples, including but not limited to, insulin-like growth factor (IGF)-I, IGF-II, insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-3.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15.

ARM II: Patients receive cixutumumab IV over 1 hour on days 1 and 15 and paclitaxel as in Arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Life expectancy >= 12 weeks
  • Women must not be pregnant or breast-feeding due to potential harm to fetus from cixutumumab (IMC-A12) and paclitaxel; all females of childbearing potential must have a blood test or urine study within 48 hours prior to registration to rule out pregnancy
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method or birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of cixutumumab (IMC-A12); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must have measurable disease
  • Patients must have metastatic disease of the esophagus or gastroesophageal junction

    • Histologic, cytologic or radiologic documentation of metastatic squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction; radiologic, endoscopic, histologic or cytologic evidence of locally recurrent or locally residual (post-resection) disease is also permitted
    • For the purposes of this study, undifferentiated adenocarcinomas and adenosquamous tumors will be considered as adenocarcinomas; in addition, tumors involving the gastroesophageal junction will be defined by the Siewert classification
  • Patients with gastroesophageal junction tumors who are eligible:

    • Adenocarcinoma of the esophageal junction (AEG) Type I: adenocarcinoma of the distal esophagus which usually arises from an area with specialized intestinal metaplasia of the esophagus, i.e., Barrett's esophagus, and may infiltrate the esophagogastric junction from above
    • AEG Type II: true carcinoma of the cardia arising from the cardiac epithelium or short segments with intestinal metaplasia at the esophagogastric junction
  • Patients with gastroesophageal junction tumors who are NOT eligible:

    • AEG Type III: subcardial gastric carcinoma which infiltrates the esophagogastric junction and distal esophagus from below
  • Patients must have received and progressed on one and only one line of prior systemic therapy for esophagus or esophagogastric cancer; this could have included one regimen for metastatic disease, or one regimen with radiotherapy for initially locally advanced disease; prior radiation therapy is permitted

    • If patients progress or recur within 6 months of neoadjuvant/adjuvant therapy, this will be considered one line of therapy; for patients progressing or recurring more than 6 months after neoadjuvant/adjuvant therapy, they will need to receive one line of therapy for recurrent disease to be eligible
    • If patients receive one regimen in which a chemotherapy agent is dropped for toxicity without progression, this treatment will be considered one line of therapy; however, substitution or addition of a new agent will be considered a second line of therapy
  • Patients may not have received prior taxane or anti-insulin growth factor receptor (IGFR) therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< institutional upper limit of normal (ULN)
  • Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN
  • Creatinine =< 1.5 X institutional ULN or creatinine clearance >= 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal
  • Patients must have fasting serum glucose =< 160 mg/dL (8.8 mmol/L) or =< ULN, and hemoglobin A1C =< 7% (0.07 International System of Units [SI units]) within 14 days of registration; if baseline nonfasting glucose =< 160 mg/dL (8.8 mmol/L), fasting glucose measurement is not required
  • Patients must not have any of the following conditions:

    • Poorly controlled diabetes mellitus; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose =< 160 mg/dL [8.8 mmol/L] or below the ULN and hemoglobin A1C =< 7% [0.07 SI units]) and that they are on a stable dietary or therapeutic regimen for this condition
    • Recent major surgery, hormonal therapy (other than replacement) or chemotherapy, within 4 weeks prior to entering the study or those who have not recovered from adverse events
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cixutumumab (IMC-A12)
    • Psychiatric illness that would prevent the patient from giving informed consent
  • Registration no fewer than 28 days from last chemotherapy
  • Medical conditions such as active/uncontrolled infection (including HIV) or cardiac disease that would make this protocol unreasonably hazardous for the patient in the opinion of the treating physician; cardiac disease may include uncontrolled high blood pressure, unstable angina, or serious uncontrolled cardiac arrhythmia
  • A "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01142388

  Show 234 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Cohen ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01142388     History of Changes
Other Study ID Numbers: NCI-2011-02045, NCI-2011-02045, CDR0000674327, ECOG-E2208, E2208, E2208, U10CA021115, U10CA180820
Study First Received: June 10, 2010
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014