A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01100931
First received: April 8, 2010
Last updated: May 3, 2013
Last verified: May 2013
  Purpose

Background:

  • Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival compared to carboplatin and paclitaxel alone. However, this trial treated only patients with a specific diagnosis and treatment risks. Further research is needed to determine whether this combination is useful for other diagnoses.
  • YM155 is a drug that targets a type of chemical often found in cancer cells. It has been investigated in several phase I and phase II clinical trials, and it has been shown to be well tolerated and moderately effective in treating advanced NSCLC in patients who had not responded well to one or two standard treatments.

Objectives:

- To determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer.

Eligibility:

- Individuals 18 years of age and older who have been diagnosed with advanced non-small-cell lung carcinoma or other solid tumors for which standard therapy is not likely to be effective.

Design:

  • Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors.
  • Participants will be treated for six 21-day cycles, or 18 weeks of treatment. Each cycle will include blood tests and imaging studies as required.
  • On day 1 of each cycle, participants will receive an infusion of paclitaxel and carboplatin, followed by a 4-day infusion of YM155 (through a portable electronic infusion pump).
  • Participants will have a computed tomography scan or other imaging every other cycle (approximately every 6 weeks) to determine whether the therapy is affecting the cancer site.
  • After the sixth cycle, participants will return for follow-up visits at least every 3 months, and will be asked to remain in contact with the researchers to allow further study of the long-term effects of the treatment.

Condition Intervention Phase
NSCLC
Solid Tumors
Drug: YM155
Drug: Carboplatin
Drug: Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Phase 1 Safe and Tolerable Phase 2 Dose. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).

    Phase 2 dose is based upon dose limiting toxicities experienced during cycle 1.


  • Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)). [ Time Frame: up to 18 weeks ] [ Designated as safety issue: Yes ]
    Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  • Number of Participants With Adverse Events [ Time Frame: 31.5 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.


Enrollment: 42
Study Start Date: February 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: YM155 in Solid Tumors

Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).

Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.

Drug: YM155

Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).

Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.

Drug: Carboplatin
Area under curve (AUC) of 6 intravenous on day 1
Other Name: Paraplatin
Drug: Paclitaxel
200 mg/m^2 intravenous on day 1
Other Name: Taxol

  Show Detailed Description

  Eligibility

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

Response should be YES

Phase 1 and 2:

  1. Has a signed consent/assent been obtained by the patient or parent/legal guardian?
  2. Is a male or female greater than or equal to 18 years old?
  3. If patient has brain metastases, is it asymptomatic and does not require steroids or antiepileptic mediations?
  4. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky > 60%)?
  5. Has adequate bone marrow, renal, and hepatic function:

    1. Absolute neutrophil count (ANC) greater than or equal to 1,500/m^3?
    2. Hemoglobin greater than or equal to 10.0g/dl?
    3. Platelets greater than or equal to 100,000/m^3?
    4. Has adequate renal function defined as serum creatinine < upper limit of normal (ULN) or calculated creatinine clearance > 60 mL/min?
    5. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times ULN?
    6. Total bilirubin less than or equal to 1.5 times ULN (in patients with evidence of Gilberts disease, elevated bilirubin should not be related to tumor or other liver diseases and should be less than or equal 2 times upper limit of normal)?
  6. Has negative human immunodeficiency virus (HIV) test?
  7. If female, has negative pregnancy test?
  8. Both male and female patients are willing to consent to using effective contraception (hormonal, barrier method or abstinence) prior to study entry, while on treatment and at least 3 months thereafter?

Phase 1 only:

  1. Has recurrent or advanced cancer for whom standard therapy offers no curative potential and also for patients for whom the carboplatin/paclitaxel regimen is considered standard of care?
  2. Has received no more than one previous chemotherapy regimen?
  3. Has evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria?

Phase 2 only:

  1. Has histological or cytological evidence of non small cell lung cancer?
  2. Has evidence of metastatic disease or stage IIIB non small cell lung cancer (NSCL) with pleural effusion is required?
  3. Has no prior chemotherapy for advanced lung cancer?

    Note: Patients who received adjuvant or neo-adjuvant chemotherapy more than 12 months prior will be eligible?

  4. Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan?

EXCLUSION CRITERIA:

Response should be NO

  1. Has any of the following within 6 months prior to study enrollment: myocardial infarction, unstable angina pectoris or uncontrolled angina pectoris, uncontrolled hypertension that is not controllable with antihypertensives, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant peripheral vascular disease (Grade II or greater).
  2. Has history of stroke or transient ischemic attack within 6 months?
  3. Has history of pulmonary embolism, deep venous thrombosis or other thrombo-embolic event within 6 months?
  4. Has psychiatric or neurologic illness that would limit compliance with study requirements?
  5. Has severe active infection within 14 days requiring use of intravenous antibiotics before beginning treatment?
  6. Has received any other investigational agents within 30 days of the start of treatment?
  7. Has history of an active malignancy unless curatively treated and risk of recurrence of < 5% at five years, with the exception of:

    1. Adequately treated in situ carcinoma of the cervix
    2. Non-melanomatous skin cancers (basal or squamous cell)?
  8. Has history of severe hypersensitivity reaction to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, or medicines of similar composition to YM155?
  9. Has history of a major surgical procedure, open biopsy, or a significant traumatic injury within 14 days prior to commencing treatment, or the anticipation of the need for a major surgical procedure during the course of the study?
  10. Has other serious illness, medical condition or significant laboratory abnormality that may cause undue risk for the subject's safety, inhibit protocol participation, or interference with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study?
  11. Phase 2 only: Has mixed tumor of any histology including small cell lung cancer?
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01100931

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Giuseppe Giaccone, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Arun Rajan, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01100931     History of Changes
Other Study ID Numbers: 100051, 10-C-0051
Study First Received: April 8, 2010
Results First Received: February 21, 2013
Last Updated: May 3, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
NSCLC
Solid Tumors
YM155
Survivin
Non Small-Cell Lung Cancer
Solid Tumor

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

ClinicalTrials.gov processed this record on April 17, 2014