NCT01633541 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2023-07-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.

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outcome · POSTED

Head and Neck Related Quality of Life (QOL)

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outcome · POSTED

Voice Related QOL

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outcome · POSTED

Functional Assessment QOL

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: AT-101
Drug: Cisplatin
Drug: Carboplatin
label
platinum/docetaxel + AT-101
type
EXPERIMENTAL
description
(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 Names
Drug: Docetaxel
Drug: Cisplatin
Drug: Carboplatin
label
Active Comparator arm
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
platinum/docetaxel + AT-101
description
Patients will receive AT-101 40 mg orally two times a day.
name
AT-101
other Names
Bcl-xL INHIBITOR
type
DRUG
arm Group Labels
Active Comparator arm
description
Docetaxel (Taxotere) 75 mg/m2
name
Docetaxel
other Names
Taxotere
type
DRUG
arm Group Labels
Active Comparator arm
platinum/docetaxel + AT-101
description
Cisplatin 100 mg/m2
name
Cisplatin
type
DRUG
arm Group Labels
Active Comparator arm
platinum/docetaxel + AT-101
description
Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg
name
Carboplatin
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 55
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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
measure
Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment
time Frame
Up to 3 months after end of treatment
description
Time from randomization to the time of first indication of local failure or metastases. Estimated non-parametrically using the Kaplan-Meier method.
measure
Progression-free Survival
time Frame
Up to 3 years after randomization
description
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.
measure
Overall Response Rate (ORR)
time Frame
Up to approximately 60 days
description
Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.
measure
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.
time Frame
Up to 3 years after end of treatment

secondary Outcomes

description
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). Scale is 0-100 with high scores indicating a better outcome.
measure
Head and Neck Related Quality of Life (QOL)
time Frame
Up to 28 months post treatment
description
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). Scale is 0-50 (10 items scale 1-5) with high scores indicating a worse outcome.
measure
Voice Related QOL
time Frame
Up to 28 months post treatment
description
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). Scale is 0-100 with high scores indicating a better outcome. EATING Domain is reported here as a functional assessment.
measure
Functional Assessment QOL
time Frame
Up to 28 months post treatment

Full study description

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.

Source references

Source notices and limitations

Discovery and provenance

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exact text
NCT01633541
start
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offset unit
unicode_code_points
query cond
Laryngeal Cancer
query disease state id
ds-laryngeal-cancer
source file
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source string sha256
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source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Laryngeal+Cancer&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice