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

NCT01633541 | Completed Phase 2 Results DMC

• 2 other identifiers: UMCC 2010.101HUM00043975
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Laryngeal Cancer

Outcome Measures

Primary Outcomes (4)

• Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post 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

  Up to 3 months after end of treatment

• Progression-free Survival

  Time from randomization to the time of first indication of local failure or metastases. Estimated non-parametrically using the Kaplan-Meier method.

  Up to 3 years after randomization

• Overall Response Rate (ORR)

  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.

  Up to approximately 60 days

• Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.

  Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.

  Up to 3 years after end of treatment

Secondary Outcomes (3)

• Head and Neck Related Quality of Life (QOL)

  Up to 28 months post treatment

• Voice Related QOL

  Up to 28 months post treatment

• Functional Assessment QOL

  Up to 28 months post treatment

Study Arms (2)

platinum/docetaxel + AT-101

EXPERIMENTAL

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.

Drug: AT-101; Drug: Cisplatin; Drug: Carboplatin

Active Comparator arm

ACTIVE COMPARATOR

(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: Docetaxel; Drug: Cisplatin; Drug: Carboplatin

Interventions

AT-101 DRUG

Patients will receive AT-101 40 mg orally two times a day.

Also known as: Bcl-xL INHIBITOR

platinum/docetaxel + AT-101

Docetaxel DRUG

Docetaxel (Taxotere) 75 mg/m2

Also known as: Taxotere

Active Comparator arm

Cisplatin DRUG

Cisplatin 100 mg/m2

Active Comparator arm; platinum/docetaxel + AT-101

Carboplatin DRUG

Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg

Active Comparator arm; platinum/docetaxel + AT-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Laryngeal Neoplasms

Interventions

gossypol acetic acid; Docetaxel; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Results Point of Contact

• Title: Dr. Paul Swiecicki
• Organization: University of Michigan Rogel Cancer Center

pswiecic@med.umich.edu

734-647-1017

Study Officials

• Paul Swiecicki, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2012
• First Posted: July 4, 2012
• Study Start: March 1, 2012
• Primary Completion: November 6, 2021
• Study Completion: November 6, 2021
• Last Updated: July 20, 2023
• Results First Posted: July 20, 2023

Record last verified: 2023-07

Locations

US (1)