Laryngeal CancerPhase 2NCT01633541
Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Organ Preservation In Adults With Advanced Laryngeal Cancer
A Phase 2 study testing AT-101, Docetaxel and Cisplatin in people with Laryngeal Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Laryngeal Cancer
- What is being tested?
- AT-101, Docetaxel and Cisplatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to 6 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: 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.
Read the 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.
- Conditions
- Laryngeal Cancer
- Being tested
- AT-101, Docetaxel, Cisplatin, Carboplatin
- Medical subject headings
- Laryngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT-101Drug
Also called Bcl-xL INHIBITOR
Patients will receive AT-101 40 mg orally two times a day.
DocetaxelDrug
Also called Taxotere
Docetaxel (Taxotere) 75 mg/m2
CisplatinDrug
Cisplatin 100 mg/m2
CarboplatinDrug
Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Docetaxel; Drug: Cisplatin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 3 years after end of treatment
Secondary outcomes (3)
Head and Neck Related Quality of Life (QOL)
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.
Measured: Up to 28 months post treatment
Voice Related QOL
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.
Measured: Up to 28 months post treatment
Functional Assessment QOL
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.
Measured: Up to 28 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2012 (estimated)
- Study startMar 2012
- Primary completion6 Nov 2021
- Study completion6 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Laryngeal CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Swiecicki, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01633541
- Sponsor's protocol ID
- UMCC 2010.101
- Other IDs
- HUM00043975
- Status last verified
- Jul 2023
- First submitted
- 29 Jun 2012
- Last updated
- 20 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer
- ClinicalTrials.gov ID
- NCT01633541
- Acronym / sponsor ID
- UMCC 2010.101
- Conditions
- Laryngeal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Mar 2012 (actual)
- Primary completion
- 6 Nov 2021 (actual)
- Study completion
- 6 Nov 2021 (actual)
- First posted
- 4 Jul 2012 (estimated)
- Results
- Posted 20 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| platinum/docetaxel + AT-101 | Experimental | Drug: AT-101, Drug: Cisplatin, Drug: Carboplatinplatinum/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. |
| Active Comparator arm | Active comparator | Drug: Docetaxel, Drug: Cisplatin, Drug: Carboplatin(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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AT-101Also: Bcl-xL INHIBITORPatients will receive AT-101 40 mg orally two times a day. | Drug | platinum/docetaxel + AT-101 |
| DocetaxelAlso: TaxotereDocetaxel (Taxotere) 75 mg/m2 | Drug | Active Comparator arm |
| CisplatinCisplatin 100 mg/m2 | Drug | Active Comparator arm, platinum/docetaxel + AT-101 |
| CarboplatinCarboplatin AUC (area under the curve) 6. Maximum dose of 700 mg | Drug | Active Comparator arm, platinum/docetaxel + AT-101 |
Primary outcome
Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment
Time frame: Up to 3 months after end of 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
Progression-free Survival
Time frame: Up to 3 years after randomization
Time from randomization to the time of first indication of local failure or metastases. Estimated non-parametrically using the Kaplan-Meier method.
Overall Response Rate (ORR)
Time frame: Up to approximately 60 days
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.
Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.
Time frame: Up to 3 years after end of treatment
Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3.
3 secondary outcomes
Head and Neck Related Quality of Life (QOL)
Time frame: Up to 28 months post treatment
Voice Related QOL
Time frame: Up to 28 months post treatment
Functional Assessment QOL
Time frame: Up to 28 months post treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Swiecicki, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AT-101, Docetaxel and Cisplatin in people with Laryngeal Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.