Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Organ Preservation In Adults With Advanced Laryngeal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01633541
Recruitment Status : Active, not recruiting
First Posted : July 4, 2012
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Tracking Information
First Submitted Date  ICMJE June 29, 2012
First Posted Date  ICMJE July 4, 2012
Last Update Posted Date December 12, 2019
Study Start Date  ICMJE March 2012
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Number of patients alive and free from indication for laryngectomy three months post treatment [ Time Frame: Up to 3 months after end of treatment ]
    The primary clinical objective of this trial is to compare the larynx preservation rates in a treatment paradigm that uses induction chemotherapy plus AT-101 to select patients for either concurrent chemoradiation or surgery. Organ preservation rate, defined as alive and free from indication for laryngectomy three months post treatment, was chosen as the primary endpoint because it provides evidence to fully characterize clinically the effect of the treatment strategy
  • Progression-free survival [ Time Frame: Up to 3 years after randomization ]
    Time from randomization to the time of first indication of local failure or metastases. Estimated non-parametrically using the Kaplan-Meier method.
  • Overall response rate (ORR) [ Time Frame: Up to approximately 60 days ]
    ORR (Complete Response [CR] plus Partial Response [PR]) to induction chemotherapy with platinum and docetaxel plus AT-101 following one and/or two cycles in patients with advanced laryngeal cancer.
  • Percentage of patients experiencing grade 3 or higher adverse events. [ Time Frame: Up to 3 years after end of treatment ]
    Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.
Original Primary Outcome Measures  ICMJE
 (submitted: July 3, 2012)
Organ preservation rate [ Time Frame: 3 months ]
The primary clinical objective of this trial is to compare the larynx preservation rates in a treatment paradigm that uses induction chemotherapy plus AT-101 to select patients for either concurrent chemoradiation or surgery. Organ preservation rate, defined as alive and free from indication for laryngectomy three months post treatment, was chosen as the primary endpoint because it provides evidence to fully characterize clinically the effect of the treatment strategy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Head and Neck Related Quality of Life (QOL) [ Time Frame: Up to 28 months post treatment ]
    University of Michigan Head and Neck Quality of Life Instrument (HN-QOL) will be administered prior to treatment (i.e. pre-induction chemotherapy) and at 6 months, 12 months, and 24 months (+/- 4 months) after completion of chemo-RT or surgery-RT (or surgery-chemoRT, as indicated).
  • Voice Related QOL [ Time Frame: Up to 28 months post treatment ]
    The University of Michigan Voice Related Quality of Life Measure (V-RQOL) will be administered prior to treatment (i.e. pre-induction chemotherapy) and at 6 months, 12 months, and 24 months (+/- 4 months) after completion of chemo-RT or surgery-RT (or surgery-chemoRT, as indicated).
  • Functional Assessment QOL [ Time Frame: Up to 28 months post treatment ]
    The Functional Assessment of Cancer Therapy Head and Neck (FACT H&N, version 4) will be administered prior to treatment (i.e. pre-induction chemotherapy) and at 6 months, 12 months, and 24 months (+/- 4 months) after completion of chemo-RT or surgery-RT (or surgery-chemoRT, as indicated).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Organ Preservation In Adults With Advanced Laryngeal Cancer
Official Title  ICMJE Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer
Brief Summary To evaluate a new treatment approach for adults with advanced laryngeal cancer: induction chemotherapy with platinum and docetaxel plus AT-101. AT-101 is an investigational drug for the treatment of advanced cancer. It is hoped that the combination of this chemotherapy regimen will allow cancer patients to keep their voice box and to improve/maintain voice-related quality of life. The ultimate goal of this study is to prevent the surgery to remove subjects voice box.
Detailed Description Published data demonstrate equal efficacy and improved quality of life when platinum and a taxane were compared with platinum and 5-Fluorouracil [31]. Additionally, weekly cisplatin regimens (30-40 mg/m2) with radiotherapy appear to be equally efficacious and better tolerated than standard high-dose cisplatin (100 mg/ m2) regimens with radiation therapy for locally advanced SCCHN [32] The investigators will thus attempt to reduce toxicity from induction chemotherapy with the use of docetaxel/cisplatin (or carboplatin) (TP) in place of our previously used standard regimen of cisplatin and 5-fluorouracil (PF) and administer weekly cisplatin (or carboplatin) with radiation for those patients who are responders to induction therapy. Finally, Phase I/II testing of the small molecule inhibitor, AT-101, has recently been completed, and suggests activity in solid tumors when combined with cytotoxic agents. Since the investigators have achieved such high survival rates with our treatment selection approach in laryngeal cancer, our ultimate goal is to reduce the rate of salvage laryngectomy which should improve quality of life. The investigators hypothesize that specific inhibition of Bcl-2/Bcl-xL function can increase response rates to neoadjuvant chemotherapy and decrease the need for salvage laryngectomy. Hence, the investigators propose this study: the treatment of patients with advanced SCC of the larynx with one cycle of platinum plus docetaxel with AT-101, followed by chemoradiotherapy for those responding to this induction regimen and reserving total laryngectomy for those who are non-responders.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Laryngeal Cancer
Intervention  ICMJE
  • Drug: AT-101
    Patients will receive AT-101 40 mg orally two times a day.
    Other Name: Bcl-xL INHIBITOR
  • Drug: Docetaxel
    Docetaxel (Taxotere) 75 mg/m2
    Other Name: Taxotere
  • Drug: Cisplatin
    Cisplatin 100 mg/m2
  • Drug: Carboplatin
    Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg
Study Arms  ICMJE
  • Experimental: platinum/docetaxal + AT-101

    platinum/docetaxel + AT-101 The platinum will either be cisplatin or carboplatin as deemed best by the medical oncologist.

    (Both Arms) Day #1: Patients will undergo induction chemotherapy with (TP) docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 (or Carboplatin AUC 6).

    (AT-101 Arm) Days #1-3: Patients will receive AT-101 40 mg orally twice daily On Day 23 (+/- 3 days), there will be a direct laryngoscopy (DL) with tumor biopsy and blood draw, repeat CT scan of the neck with perfusion within a week biopsy.

    Interventions:
    • Drug: AT-101
    • Drug: Cisplatin
    • Drug: Carboplatin
  • Active Comparator: Active Comparator arm

    (Both Arms) Day #1: Patients will undergo induction chemotherapy with (TP) docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 (or Carboplatin AUC 6).

    Day #23 (+/- 3 days): Patients will undergo a direct laryngoscopy (DL) with biopsy. Patients will also undergo a repeat CT scan of the neck with perfusion within a week (+/-) of their perspective biopsies.

    Interventions:
    • Drug: Docetaxel
    • Drug: Cisplatin
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 28, 2018)
59
Original Estimated Enrollment  ICMJE
 (submitted: July 3, 2012)
52
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have pathologically confirmed, previously untreated, resectable, squamous cell carcinoma of the larynx or hypopharynx.
  • Disease must be Stage III or IV
  • Tumor must be potentially surgically resectable and curable with conventional surgery and radiation therapy
  • Patients must undergo pre-treatment endoscopic tumor staging and CT scanning
  • ECOG Performance status 0-1
  • Adequate WBC (white blood cell), granulocyte and platelet counts
  • Creatinine clearance of ≥ 60cc/min for cisplatin candidates and ≥ 30 cc/min for carboplatin candidates
  • Adequate bilirubin, AST (aspartate aminotransferase), and ALT (alanine transaminase) function

Exclusion Criteria:

  • Prior head and neck malignancy or history of other prior non-head and neck malignancy within the past 3 years
  • Prior head and neck radiation or prior chemotherapy.
  • Documented evidence of distant metastases
  • Active infection
  • Pregnancy or lactation
  • Any medical or psychiatric illness which in the opinion of the principal investigator would compromise the patient's ability to tolerate this treatment
  • Patients residing in prison
  • Patients with psychiatric/ social situations that would limit compliance with study requirements
  • Patients with Grade > 2 peripheral neuropathy
  • History of severe hypersensitivity reaction to docetaxel
  • Class 3 or 4 cardiac disease
  • Unstable angina or history of myocardial ischemia within prior 6 months
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, inflammatory bowel disease, partial or complete small bowel obstruction
  • Prior use of gossypol or AT-101, or known hypersensitivity to gossypol or AT-101
  • Patients taking any other concurrent approved or investigational anti-cancer therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01633541
Other Study ID Numbers  ICMJE UMCC 2010.101
HUM00043975 ( Other Identifier: University of Michigan IRBMED )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Michigan Rogel Cancer Center
Study Sponsor  ICMJE University of Michigan Rogel Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul Swiecicke, MD University of Michigan Rogel Cancer Center
PRS Account University of Michigan Rogel Cancer Center
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP