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
  Purpose

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.


Condition Intervention Phase
Laryngeal Cancer
Drug: AT-101
Drug: Chemotherapy with Docetaxel and cisplatin (/or carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: UMCC 2010.101 Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • 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


Estimated Enrollment: 52
Study Start Date: March 2012
Estimated Study Completion Date: January 2015
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: AT-101
Patients will receive AT-101 40 mg orally two times a day.
Other Name: Bcl-xL INHIBITOR
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.

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

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.

  Eligibility

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

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
  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: NCT01633541

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Francis (Frank) Worden
Investigators
Principal Investigator: Frank Worden, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Francis (Frank) Worden, Principal Investigator, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01633541     History of Changes
Other Study ID Numbers: UMCC 2010.101, HUM 43975
Study First Received: June 29, 2012
Last Updated: June 21, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Laryngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Gossypol acetic acid
Docetaxel
Cisplatin
Carboplatin
Gossypol
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Contraceptive Agents, Female
Spermatocidal Agents
Antispermatogenic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014