Laryngeal Cancer
Conditions
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.
Interventions
DRUGAT-101
Patients will receive AT-101 40 mg orally two times a day.
DRUGDocetaxel
Docetaxel (Taxotere) 75 mg/m2
DRUGCisplatin
Cisplatin 100 mg/m2
DRUGCarboplatin
Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment | 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 | 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) | 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. | Up to 3 years after end of treatment | Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Voice Related QOL | Up to 28 months post treatment | 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. |
| Functional Assessment QOL | Up to 28 months post treatment | 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. |
| Head and Neck Related Quality of Life (QOL) | Up to 28 months post treatment | 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. |
Countries
United States
Participant flow
Pre-assignment details
one subject was enrolled; however, disease progression was discovered before active treatment and therefore the patient never was treated with study drug
Participants by arm
| Arm | Count |
|---|---|
| Platinum/Docetaxal + AT-101 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.
AT-101: Patients will receive AT-101 40 mg orally two times a day.
Cisplatin: Cisplatin 100 mg/m2
Carboplatin: Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg
Per physician discretion, carboplatin was used in lieu of cisplatin for 13 patients in this arm | 36 |
| 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.
Docetaxel: Docetaxel (Taxotere) 75 mg/m2
Cisplatin: Cisplatin 100 mg/m2
Per physician discretion, carboplatin was used in lieu of cisplatin for 10 patients in this arm Carboplatin: Carboplatin AUC (area under the curve) 6. Maximum dose of 700 mg | 18 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Active Comparator Arm | Total | Platinum/Docetaxal + AT-101 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 16 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 38 Participants | 27 Participants |
| Age, Continuous | 61.4 years | 59.95 years | 58.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 53 Participants | 35 Participants |
| Region of Enrollment United States | 18 participants | 54 participants | 36 participants |
| Sex: Female, Male Female | 0 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Male | 18 Participants | 46 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 36 | 1 / 18 |
| other Total, other adverse events | 36 / 36 | 18 / 18 |
| serious Total, serious adverse events | 14 / 36 | 5 / 18 |
Outcome results
Primary
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
Time frame: Up to 3 months after end of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Platinum/Docetaxal + AT-101 | Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment | 27 Participants |
| Active Comparator Arm | Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment | 12 Participants |
Primary
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.
Time frame: Up to approximately 60 days
Population: This outcome measure only applies to those subjects treated with induction chemotherapy with platinum and docetaxel plus AT-101 and therefore only one arm is being reported
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Platinum/Docetaxal + AT-101 | Overall Response Rate (ORR) | 27 Participants |
Primary
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.
Time frame: Up to 3 years after end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Platinum/Docetaxal + AT-101 | Percentage of Patients Experiencing Grade 3 or Higher Adverse Events. | 61 percentage of Patients |
| Active Comparator Arm | Percentage of Patients Experiencing Grade 3 or Higher Adverse Events. | 44 percentage of Patients |
Primary
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.
Time frame: Up to 3 years after randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Platinum/Docetaxal + AT-101 | Progression-free Survival | 55 percentage of participants |
| Active Comparator Arm | Progression-free Survival | 65 percentage of participants |
Secondary
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.
Time frame: Up to 28 months post treatment
Population: Number of participants analyzed varies below based on completion compliance
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Platinum/Docetaxal + AT-101 | Functional Assessment QOL | EATING- Prior to treatment | 83.3 score on a scale |
| Platinum/Docetaxal + AT-101 | Functional Assessment QOL | EATING- 6 months | 75 score on a scale |
| Platinum/Docetaxal + AT-101 | Functional Assessment QOL | EATING- 12 months | 83.3 score on a scale |
| Platinum/Docetaxal + AT-101 | Functional Assessment QOL | EATING- 24 months | 77.1 score on a scale |
| Active Comparator Arm | Functional Assessment QOL | EATING- 24 months | 95.8 score on a scale |
| Active Comparator Arm | Functional Assessment QOL | EATING- Prior to treatment | 91.7 score on a scale |
| Active Comparator Arm | Functional Assessment QOL | EATING- 12 months | 83.3 score on a scale |
| Active Comparator Arm | Functional Assessment QOL | EATING- 6 months | 83.3 score on a scale |
Secondary
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.
Time frame: Up to 28 months post treatment
Population: Number of participants analyzed varies below based on completion compliance
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Emotion- Prior to treatment | 66.7 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Emotion- 6 months | 66.7 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Emotion- 12 months | 72.9 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Emotion- 24 months | 75 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Speech- Prior to treatment | 46.9 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Speech- 6 Months | 56.3 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Speech- 12 Months | 50 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Speech- 24 Months | 50 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Pain- Prior to treatment | 59.4 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Pain- 6 months | 62.5 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Pain- 12 months | 68.8 units on a scale |
| Platinum/Docetaxal + AT-101 | Head and Neck Related Quality of Life (QOL) | Pain- 24 months | 56.3 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Pain- 12 months | 62.5 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Emotion- Prior to treatment | 62.5 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Speech- 12 Months | 62.5 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Emotion- 6 months | 95.8 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Pain- 6 months | 81.3 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Emotion- 12 months | 91.7 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Speech- 24 Months | 75 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Emotion- 24 months | 91.7 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Pain- 24 months | 87.5 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Speech- Prior to treatment | 34.4 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Pain- Prior to treatment | 68.8 units on a scale |
| Active Comparator Arm | Head and Neck Related Quality of Life (QOL) | Speech- 6 Months | 50 units on a scale |
Secondary
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.
Time frame: Up to 28 months post treatment
Population: number of participants analyzed varies due to patient compliance and patients coming off trial per protocol
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Platinum/Docetaxal + AT-101 | Voice Related QOL | WHATCOMEOUT_VAL_3n- 6 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | NOISY_VAL_- 12 months | 4 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | DEPRESSED_VAL_5n- 24 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | WHATCOMEOUT_VAL_3n- Prior to treatment | 1 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEPHONE_VAL_6n- Prior to treatment | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | VRQOL-SUM- 12 Months | 26 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEPHONE_VAL_6n- 6 Months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | WHATCOMEOUT_VAL_3n- 12 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEPHONE_VAL_6n- 12 Months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | NOISY_VAL_- 24 months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEPHONE_VAL_6n- 24 Months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | WHATCOMEOUT_VAL_3n- 24 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEJOB_VAL_7n- Prior to treatment | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | NOISY_VAL_- Prior to treatment | 4 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEJOB_VAL_7n- 6 Months | 1 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | ANXIOUS_VAL_4n- Prior to treatment | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEJOB_VAL_7n- 12 Months | 2.5 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | OUTOFAIR_VAL- Prior to treatment | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | TROUBLEJOB_VAL_7n- 24 Months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | ANXIOUS_VAL_4n- 6 months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- Prior to treatment | 1 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | VRQOL-SUM- 6 Months | 23 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- 6 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | ANXIOUS_VAL_4n- 12 months | 2.5 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- 12 months | 1.5 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | OUTOFAIR_VAL- 6 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- 24 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | ANXIOUS_VAL_4n- 24 months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | REPEATMYSELF_VAL_9n- Prior to treatment | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | NOISY_VAL_- 6months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | REPEATMYSELF_VAL_9n- 6 months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | DEPRESSED_VAL_5n- Prior to treatment | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | REPEATMYSELF_VAL_9n- 12 months | 3 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | OUTOFAIR_VAL- 12 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | REPEATMYSELF_VAL_9n- 24 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | DEPRESSED_VAL_5n- 6 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | LESSOUTGOING_VAL_10n- Prior to treatment | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | VRQOL-SUM- 24 Months | 22 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | LESSOUTGOING_VAL_10n- 6 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | DEPRESSED_VAL_5n- 12 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | LESSOUTGOING_VAL_10n- 12 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | OUTOFAIR_VAL- 24 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | LESSOUTGOING_VAL_10n- 24 months | 2 score on a scale |
| Platinum/Docetaxal + AT-101 | Voice Related QOL | VRQOL-SUM- Prior to treatment | 25 score on a scale |
| Active Comparator Arm | Voice Related QOL | LESSOUTGOING_VAL_10n- 24 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | VRQOL-SUM- Prior to treatment | 24 score on a scale |
| Active Comparator Arm | Voice Related QOL | VRQOL-SUM- 6 Months | 23 score on a scale |
| Active Comparator Arm | Voice Related QOL | VRQOL-SUM- 12 Months | 22 score on a scale |
| Active Comparator Arm | Voice Related QOL | VRQOL-SUM- 24 Months | 21 score on a scale |
| Active Comparator Arm | Voice Related QOL | NOISY_VAL_- Prior to treatment | 4 score on a scale |
| Active Comparator Arm | Voice Related QOL | NOISY_VAL_- 6months | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | NOISY_VAL_- 12 months | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | NOISY_VAL_- 24 months | 4 score on a scale |
| Active Comparator Arm | Voice Related QOL | OUTOFAIR_VAL- Prior to treatment | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | OUTOFAIR_VAL- 6 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | OUTOFAIR_VAL- 12 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | OUTOFAIR_VAL- 24 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | WHATCOMEOUT_VAL_3n- 6 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | WHATCOMEOUT_VAL_3n- 12 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | WHATCOMEOUT_VAL_3n- 24 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | ANXIOUS_VAL_4n- Prior to treatment | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | ANXIOUS_VAL_4n- 6 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | ANXIOUS_VAL_4n- 12 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | ANXIOUS_VAL_4n- 24 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | DEPRESSED_VAL_5n- Prior to treatment | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | DEPRESSED_VAL_5n- 6 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | WHATCOMEOUT_VAL_3n- Prior to treatment | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | DEPRESSED_VAL_5n- 12 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | DEPRESSED_VAL_5n- 24 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEPHONE_VAL_6n- Prior to treatment | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEPHONE_VAL_6n- 6 Months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEPHONE_VAL_6n- 12 Months | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEPHONE_VAL_6n- 24 Months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEJOB_VAL_7n- Prior to treatment | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEJOB_VAL_7n- 6 Months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEJOB_VAL_7n- 12 Months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | TROUBLEJOB_VAL_7n- 24 Months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- Prior to treatment | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- 6 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- 12 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | AVOIDSOCIALLY_VAL_8n- 24 months | 1 score on a scale |
| Active Comparator Arm | Voice Related QOL | REPEATMYSELF_VAL_9n- Prior to treatment | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | REPEATMYSELF_VAL_9n- 6 months | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | REPEATMYSELF_VAL_9n- 12 months | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | REPEATMYSELF_VAL_9n- 24 months | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | LESSOUTGOING_VAL_10n- Prior to treatment | 3 score on a scale |
| Active Comparator Arm | Voice Related QOL | LESSOUTGOING_VAL_10n- 6 months | 2 score on a scale |
| Active Comparator Arm | Voice Related QOL | LESSOUTGOING_VAL_10n- 12 months | 2 score on a scale |