Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Collaborators:
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005838
First received: June 2, 2000
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. AE-941 may help shrink or slow the growth of non-small cell lung cancer cells. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without AE-941 for non-small cell lung cancer. This randomized phase III trial is studying combination chemotherapy and radiation therapy given with AE-941 to see how well they work compared to combination chemotherapy and radiation therapy alone in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery


Condition Intervention Phase
Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Large Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Drug: shark cartilage extract AE-941
Other: placebo
Drug: cisplatin
Drug: vinorelbine tartrate
Drug: carboplatin
Drug: paclitaxel
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Multicenter, Open-Ended, Double-Blind, Placebo-Controlled, Phase III Study of AE-941 in Addition to Combined Modality Treatment (Chemotherapy/Radiotherapy) for Locally Advanced Unresectable Non-Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall survival [ Time Frame: From randomization until date of death or last follow-up, assessed up to 7 years ] [ Designated as safety issue: No ]
    Survival distributions will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted to illustrate the comparative survival experience of both groups over the entire study period.


Secondary Outcome Measures:
  • Progression-free survival every 3 months [ Time Frame: From randomization until disease progression, assessed up to 7 years ] [ Designated as safety issue: No ]
    Will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted.

  • Tumor response rate [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Will be compared by chi-square test.

  • Tumor response duration [ Time Frame: From first observation of at least a partial response to detection of disease progression or death due to any cause, assessed up to 7 years ] [ Designated as safety issue: No ]
    Will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted.

  • Metastasis-free survival [ Time Frame: From randomization until metastasis documented by imaging procedures, assessed up to 7 years ] [ Designated as safety issue: No ]
    Will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted.


Enrollment: 756
Study Start Date: March 2000
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (shark cartilage extract AE-941)

Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.

All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.

All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.

Drug: shark cartilage extract AE-941
Given orally
Other Names:
  • AE-941
  • Neovastat
  • Neovastat/AE-941
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Placebo Comparator: Arm II (placebo)

Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.

All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.

All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.

Other: placebo
Given orally
Other Name: PLCB
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the overall survival of patients with unresectable stage IIIA or IIIB non-small cell lung cancer treated with induction platinum-based chemotherapy and radiotherapy with or without AE-941 (Neovastat).

II. Determine the progression-free survival, tumor response, tumor response duration, and metastasis-free survival of patients treated with these regimens.

III. Determine the tolerability of this regimen in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to stage (IIIA vs IIIB), type of platinum-based induction chemotherapy to be received (cisplatin and vinorelbine vs carboplatin and paclitaxel), and gender. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.

Arm II: Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.

All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.

All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 756 patients (378 per treatment arm) will be accrued for this study within 36 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed newly diagnosed, untreated, unresectable stage IIIA or stage IIIB non-small cell lung cancer

    • Squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung
    • Mixed tumors allowed if non-small cell elements identified
    • Contralateral supraclavicular and/or scalene lymph node involvement allowed
    • No disease extending into the cervical region
  • At least 1 bidimensionally or unidimensionally measurable lesion
  • No pleural effusion unless cytologically negative or too small to safely aspirate
  • Not scheduled for curative cancer surgery
  • Performance status - ECOG 0-1
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3
  • Hematocrit greater than 30%
  • SGOT or SGPT less than 1.5 times upper limit of normal
  • Bilirubin normal
  • Creatinine less than 1.5 mg/dL
  • Creatinine clearance greater than 60 mL/min
  • No other major medical or psychiatric illness that would preclude study participation or consent
  • No medical condition that interferes with oral medication intake and/or absorption (gastrectomy or major intestinal resection)
  • No grade 2 or greater peripheral neuropathy unless secondary to mechanical etiology
  • No hypersensitivity to fish products
  • No more than 10% weight loss within past 3 months
  • No other malignancy within past 3 years except inactive carcinoma in situ of the cervix or nonmelanoma skin cancer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • At least 30 days since prior chemotherapy
  • See Disease Characteristics
  • Recovered from prior major surgery
  • At least 30 days since prior shark cartilage products
  • No other concurrent investigational anticancer agents
  • No other concurrent cartilage products
  • No other concurrent investigational agents
  • No concurrent amifostine or other radioprotectants
  • No concurrent enrollment in other clinical trials
  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: NCT00005838

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Charles Lu M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005838     History of Changes
Other Study ID Numbers: NCI-2012-02725, ID99-303, U10CA045809, CDR0000067853
Study First Received: June 2, 2000
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Vinorelbine
Cisplatin
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 19, 2014