Clinical trial NCT01633541: Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Organ Preservation In Adults With Advanced Laryngeal Cancer
Official title: Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Laryngeal Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2012-07-04
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment
timeFrame: Up to 3 months after end of treatment
measure: Progression-free Survival
timeFrame: Up to 3 years after randomization
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 60 days
measure: Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.
timeFrame: Up to 3 years after end of treatment
Secondary outcomes:
measure: Head and Neck Related Quality of Life (QOL)
timeFrame: Up to 28 months post treatment
measure: Voice Related QOL
timeFrame: Up to 28 months post treatment
measure: Functional Assessment QOL
timeFrame: Up to 28 months post treatment
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Paul Swiecicki, MD
role: PRINCIPAL_INVESTIGATOR
References: