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

This study has suspended participant recruitment.
(drug potency expiration and Ascenta's inability to manufacture more drug)
Sponsor:
Information provided by (Responsible Party):
Francis (Frank) Worden, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01633541
First received: June 29, 2012
Last updated: June 21, 2013
Last verified: June 2013

June 29, 2012
June 21, 2013
March 2012
March 2013   (final data collection date for primary outcome measure)
Organ preservation rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
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
Same as current
Complete list of historical versions of study NCT01633541 on ClinicalTrials.gov Archive Site
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Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Organ Preservation In Adults With Advanced Laryngeal Cancer
UMCC 2010.101 Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Laryngeal Cancer
  • Drug: AT-101
    Patients will receive AT-101 40 mg orally two times a day.
    Other Name: Bcl-xL INHIBITOR
  • Drug: Chemotherapy with Docetaxel and cisplatin (/or carboplatin
    chemotherapy with (TP) docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 (or Carboplatin AUC 6).
    Other Names:
    • Taxotere
    • AUC 6
    • TP
  • Experimental: platinum/docetaxal + AT-101

    platinum/docetaxal + 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.

    Intervention: Drug: AT-101
  • 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.

    Intervention: Drug: Chemotherapy with Docetaxel and cisplatin (/or carboplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
52
January 2015
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have pathologically confirmed, previously untreated, resectable, squamous cell carcinoma of the larynx
  • 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

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 Grade > 2 peripheral neuropathy
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01633541
UMCC 2010.101, HUM 43975
Yes
Francis (Frank) Worden, University of Michigan Cancer Center
Francis (Frank) Worden
Not Provided
Principal Investigator: Frank Worden, MD University of Michigan Cancer Center
University of Michigan Cancer Center
June 2013

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