Anaplastic Thyroid Cancer
Conditions
Keywords
Anaplastic Thyroid Cancer, Neoplasm, Tumor, Anti-neoplastic Agent, First-line treatment of advanced Anaplastic thyroid cancer
Brief summary
The Phase I/II study will be conducted as an open label, multiple center study of CS-7017, an experimental drug and paclitaxel chemotherapy in subjects with advanced anaplastic thyroid cancer. Biopsies will be obtained from patients with accessible tumor at baseline, two-weeks after the first CS-7017 dosage (prior to the start of combination therapy) and at the end of the first study cycle (week 3 of combination therapy), in order to evaluate the effects of the study drug alone and in combination with the chemotherapy agent on the tumor. Treatment will continue until disease progression or the development of intolerable toxicities.
Interventions
DRUGCS-7017
At Phase 1, CS-7017 will be tested in combination with paclitaxel at the following dosage levels: 0.15, 0.30, or 0.50 mg BID. At Phase 2, CS-7017 will be administered at the recommended phase 2 dose (RP2D).
DRUGPaclitaxel
Commercially available paclitaxel will be administrated as IV infusion over 3 hours once every 3 weeks.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
During the Phase 1 and Phase 2 portions of the study, participant eligibility criteria are identical except for prior treatment for anaplastic thyroid cancer (ATC). During Phase 1, eligible participants may have received prior chemotherapy while during Phase 2, eligible participants must be chemotherapy naïve. Inclusion Criteria: * Histologically or cytologically diagnosed, advanced ATC * Measurable lesion(s) * Lesion(s) (primary or metastatic) with viable tumor tissue accessible for repeated biopsy * Age equal to or older than 18 years * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 * Adequate organ and bone marrow function * Agreement to use effective contraception while on treatment and for equal to or greater than 3 months after end of treatment * Pregnant or breastfeeding
Exclusion criteria
* Medical history of diabetes mellitus requiring treatment with insulin or oral agents; no pleural or pericardial effusion or clinically significant pulmonary or cardiovascular disease. * Clinically active brain metastasis, uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis * Clinically significant active infection requiring antibiotic or antiretroviral therapy * Concomitant use of other thiazolidinediones (TZDs)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Progression-free Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | From baseline up to disease progression or death, up to approximately 2 years postdose | Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions. |
| Overall Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | From baseline up to date of death, up to approximately 2 years postdose | Overall survival (OS) was defined as the time from the date enrollment to the date of death. |
| Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | From baseline up to disease progression or the development of unacceptable toxicity, up to approximately 2 years postdose | The best overall response was the best response (in the order of confirmed complete response \[CR\], confirmed partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no tumor assessment after the date of enrollment, the best overall response is classified as Unknown. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | From baseline up to 30 days after last dose, up to approximately 2 years | Treatment-emergent adverse events (TEAEs) are defined as adverse events that started or worsened after the first dose of any study drug (after Day 1 or first day of CS-7017 monotherapy) but adverse events occurring more than 30 days after the last dose are not considered TEAEs unless also considered to be related (possibly, probably, or definitely) to study drug. |
Countries
United States
Participant flow
Recruitment details
A total of 19 participants who met all inclusion and no exclusion criteria were enrolled in the study; 15 received treatment. Due to low enrollment, no participant had a dose limiting toxicity, therefore a maximum tolerated dose required for the recommendation of Phase 2 dose could not be established. Therefore, the study was halted prematurely.
Pre-assignment details
Sequential cohorts per dose level were treated with CS-7017 and paclitaxel in accordance with prospectively defined dose levels, dose escalation rules, and definitions of treatment-related dose-limiting toxicity (DLT).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1; 0.15 mg CS-7017 Participants who received 0.15 mg BID oral CS-7017 and 135 \[Dose Level 1a\] or 175 \[Dose Level 1b\] mg/m\^2 IV paclitaxel once every 3 weeks. | 7 |
| Cohort 2; 0.30 mg CS-7017 Participants who received 0.30 mg BID oral CS-7017 and 175 mg/m\^2 IV paclitaxel once every 3 weeks. | 6 |
| Cohort 3; 0.50 mg CS-7017 Participants who received 0.50 mg BID oral CS-7017 and 175 mg/m\^2 IV paclitaxel once every 3 weeks. | 2 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Disease progression | 6 | 7 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 2; 0.30 mg CS-7017 | Cohort 3; 0.50 mg CS-7017 | Cohort 1; 0.15 mg CS-7017 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 0 Participants | 5 Participants | 9 Participants |
| Age, Continuous | 59.8 years STANDARD_DEVIATION 8.75 | 73.5 years STANDARD_DEVIATION 0.71 | 58.6 years STANDARD_DEVIATION 12.79 | 61.1 years STANDARD_DEVIATION 11.11 |
| Region of Enrollment United States | 6 participants | 2 participants | 7 participants | 15 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 7 | 6 / 6 | 0 / 2 |
| other Total, other adverse events | 6 / 7 | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 3 / 7 | 3 / 6 | 2 / 2 |
Outcome results
Primary
Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
The best overall response was the best response (in the order of confirmed complete response \[CR\], confirmed partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no tumor assessment after the date of enrollment, the best overall response is classified as Unknown.
Time frame: From baseline up to disease progression or the development of unacceptable toxicity, up to approximately 2 years postdose
Population: PFS was assessed in the Efficacy Analysis Set. Since the study halted prematurely due to low enrollment and failed to establish a recommendation for a Phase 2 dose, it was not feasible to analyze the primary outcomes per arm. The arms were combined post hoc based on these circumstances and primary efficacy outcomes were assessed in all patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Patients | Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Confirmed complete response (CR) | 0 Participants |
| All Patients | Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Confirmed partial response (PR) | 1 Participants |
| All Patients | Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Stable disease | 8 Participants |
| All Patients | Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Progressive disease | 4 Participants |
| All Patients | Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Unknown | 2 Participants |
| All Patients | Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Objective response (confirmed CR + PR) | 1 Participants |
Primary
Overall Progression-free Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions.
Time frame: From baseline up to disease progression or death, up to approximately 2 years postdose
Population: PFS was assessed in the Efficacy Analysis Set. Since the study halted prematurely due to low enrollment and failed to establish a recommendation for a Phase 2 dose, it was not feasible to analyze the primary outcomes per arm. The arms were combined post hoc based on these circumstances and primary efficacy outcomes were assessed in all patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Patients | Overall Progression-free Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | 55.5 days |
Primary
Overall Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
Overall survival (OS) was defined as the time from the date enrollment to the date of death.
Time frame: From baseline up to date of death, up to approximately 2 years postdose
Population: PFS was assessed in the Efficacy Analysis Set. Since the study halted prematurely due to low enrollment and failed to establish a recommendation for a Phase 2 dose, it was not feasible to analyze the primary outcomes per arm. The arms were combined post hoc based on these circumstances and primary efficacy outcomes were assessed in all patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Patients | Overall Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | 130.0 days |
Secondary
Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
Treatment-emergent adverse events (TEAEs) are defined as adverse events that started or worsened after the first dose of any study drug (after Day 1 or first day of CS-7017 monotherapy) but adverse events occurring more than 30 days after the last dose are not considered TEAEs unless also considered to be related (possibly, probably, or definitely) to study drug.
Time frame: From baseline up to 30 days after last dose, up to approximately 2 years
Population: TEAEs were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Neutrophil count decreased | 0 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Anaphylatic reaction | 0 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Any Severe TEAE of Grade ≥3 | 3 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Septic shock | 1 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Pneumonia | 0 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Dyspnoea | 0 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Dysphagia | 1 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Anaemia | 0 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Loss of consciousness | 0 Participants |
| All Patients | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Disease progression | 2 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Disease progression | 0 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Any Severe TEAE of Grade ≥3 | 5 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Anaemia | 1 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Dysphagia | 0 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Anaphylatic reaction | 0 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Pneumonia | 1 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Septic shock | 0 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Neutrophil count decreased | 1 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Loss of consciousness | 0 Participants |
| Cohort 2; 0.30 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Dyspnoea | 1 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Disease progression | 0 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Any Severe TEAE of Grade ≥3 | 2 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Neutrophil count decreased | 0 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Dysphagia | 0 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Dyspnoea | 0 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Loss of consciousness | 1 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Pneumonia | 0 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Anaphylatic reaction | 1 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Anaemia | 0 Participants |
| Cohort 3; 0.50 mg CS-7017 | Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC) | Septic shock | 0 Participants |