Phase II Study of Combination of Paclitaxel Poliglumex and Alimta for Advanced Non-small Cell Lung Cancer (NSCLC)

This study has been completed.
Sponsor:
Collaborator:
CTI BioPharma
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00487669
First received: June 14, 2007
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

This is a non-randomized, single-arm, single-institution, open label, two-stage phase II and dose-ranging study designed to evaluate the efficacy and safety of paclitaxel poliglumex in combination with pemetrexed in patients with advanced stage IIIB or stage IV NSCLC.


Condition Intervention Phase
Advanced Non-small Cell Lung Cancer
Drug: paclitaxel poliglumex, pemetrexed
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Combination of Paclitaxel Poliglumex (CT-2103, Xyotax) and Pemetrexed (Alimta) for the Treatment of Patients With Advanced Non-small Cell Lung Cancer.

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • To Evaluate the Overall Response Rate (Complete Plus Partial Responses by RECIST Criteria) to the Combination of Paclitaxel Poliglumex and Pemetrexed as Therapy in Patients With Advanced NSCLC. [ Time Frame: CT or MRI scans of the chest will be obtained after every 2 cycles (6-week intervals +/- 7 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Progression [ Time Frame: time from study entry until the first documented sign of progression ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: time from study entry until death ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: October 2006
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel Poliglumex with Pemetrexed
The first 6 eligible patients will be enrolled at a dose of 135 mg/m2 paclitaxel poliglumex in combination with 500 mg/m2 of pemetrexed. Patients who experience disease progression without dose-limiting adverse events after the initial cycle will be replaced. Dose escalation to the next dose level can occur provided that no more than 1 of 6 patients experience in initial dose limiting toxicity (IDLT) following 2 cycles of therapy. If ≥ 2 of 6 patients experience IDLTs at the 135 mg/m2 dose, the maximally tolerated dose (MTD) was surpassed and the study will be discontinued.
Drug: paclitaxel poliglumex, pemetrexed
The first 6 eligible patients will be enrolled at a dose of 135 mg/m2 paclitaxel poliglumex in combination with 500 mg/m2 of pemetrexed. Patients who experience disease progression without dose-limiting adverse events after the initial cycle will be replaced. Dose escalation to the next dose level can occur provided that no more than 1 of 6 patients experience in initial dose limiting toxicity (IDLT) following 2 cycles of therapy. If ≥ 2 of 6 patients experience IDLTs at the 135 mg/m2 dose, the maximally tolerated dose (MTD) was surpassed and the study will be discontinued
Other Names:
  • Xyotax
  • Alimta

Detailed Description:

Primary objective

To evaluate the overall response rate (complete plus partial responses by RECIST criteria) to the combination of paclitaxel poliglumex and pemetrexed as therapy in patients with advanced NSCLC.

Secondary Objectives

To evaluate the safety and adverse event profile of the combination of paclitaxel poliglumex and pemetrexed as therapy in patients with advanced NSCLC.

To evaluate the duration of response, time to progression, and overall survival of advanced NSCLC treated with the combination of paclitaxel poliglumex and pemetrexed.

To compare the overall response rate using three-dimensional reconstruction of target lesions by Medical Metrx Solutions (MMS) and RECIST criteria.

  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 diagnosis of locally advanced and/or metastatic NSCLC (Stage IIIB or IV).
  • Bidimensionally measurable lesions or unidimensionally evaluable lesions.
  • Age ≥ 18 years.
  • At least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST), which has not been previously treated with local therapy (e.g. radiation therapy, chemoembolization, surgery, etc.).
  • May have received prior chemotherapy (including taxanes) for advanced NSCLC.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Life expectancy > 12 weeks.
  • No active infections.
  • Adequate liver and bone marrow function.
  • AST<2.5 x ULN, bilirubin <1.5x ULN, alkaline phosphatase<2.5 x ULN (unless bone origin and no liver metastases are documented).
  • ANC ≥ 1,500/uL, platelet count ≥ 100,000/uL.
  • Normal PT and PTT.
  • Bisphosphates initiated prior to study entry will be permitted. However, initiation of bisphosphonates following study entry is not permitted.
  • Patients with treated brain metastases must be neurologically stable.
  • At least 3 weeks since last chemotherapy and recovered from treatment-related adverse events ≤ grade 1.
  • At least 3 weeks since prior radiation and recovered from treatment-related adverse events ≤ grade 1.
  • Women of childbearing potential are eligible for the study, provided they have a negative serum or urine pregnancy test within three days of study entry, and an adequate method of contraception is used. Acceptable methods of birth control include barrier methods (condoms, diaphragms with spermicide) or intrauterine devices (IUD). Women whose sole sexual partner is infertile, or who are not sexually active, are also eligible.
  • Able to provide written informed consent.

Exclusion Criteria:

  • Grade 2 or greater peripheral neuropathy, according to the National Cancer Institute-Common Toxicity Criteria.
  • Clinically significant pleural, pericardial or abdominal effusions.
  • Untreated brain metastases.
  • Patients with previously diagnosed brain metastases will be eligible if they are neurologically stable and have recovered from the effects of radiotherapy or surgery (≤ grade 2).
  • Patients with brain metastases must have at least one other site of measurable disease.
  • Concurrent radiotherapy.
  • Other concurrent cancer treatment-related investigational agent. Investigational supportive care medications are permitted.
  • Concurrent treatment with unfractionated heparin or warfarin.
  • History of radiotherapy encompassing greater than 50% of the marrow-bearing skeleton.
  • Prior bone marrow or stem cell transplant.
  • History of other active malignancy within the last year requiring chemotherapy, not including curatively-treated carcinoma in situ of the cervix, or non-melanoma skin cancer (basal cell carcinoma or squamous cell carcinoma).
  • Uncontrolled infection.
  • Active bleeding, or history of bleeding requiring transfusion within 2 weeks of study entry.
  • Active cardiac disease, as defined as:
  • Current history of uncontrolled or symptomatic angina.
  • History of arrhythmias requiring medications or clinically significant arrhythmias, with the exception of uncomplicated atrial fibrillation.
  • Myocardial infarction < 6 months from study entry.
  • Any other cardiac conditions, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
  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: NCT00487669

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
CTI BioPharma
Investigators
Principal Investigator: James R Rigas, MD Norriss Cotten Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00487669     History of Changes
Other Study ID Numbers: D-0433
Study First Received: June 14, 2007
Results First Received: November 21, 2013
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
paclitaxel poliglumex
xyotax
alimta
advanced non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Pemetrexed
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 22, 2014