Pancreatic Cancer
Conditions
Keywords
TH-302, Nab-paclitaxel, Gemcitabine, Evofosfamide
Brief summary
This is a multicenter, open-label, Phase 1, dose escalation trial to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of TH-302 in combination with gemcitabine and nab-paclitaxel in previously untreated subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma.
Interventions
DRUGTH-302
TH-302 will be administered at a dose ranging from 170-340 milligram per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.
DRUGNab-paclitaxel
Nab-paclitaxel will be administered at a dose ranging from 100-125 mg/m\^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.
DRUGGemcitabine
Gemcitabine will be administered at a dose ranging from 800-1000 mg/m\^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Sponsors
Threshold Pharmaceuticals
ImmunoGenesis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects greater than or equal to (\>=) 18 years of age with locally advanced unresectable or metastatic pancreatic adenocarcinoma proven by histology or cytology and previously untreated with chemotherapy or systemic therapy other than: * Radiosensitizing doses of 5-fluorouracil; * Radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after completion of gemcitabine; * Neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical resection; * Adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy * Subjects may have measurable or non-measurable disease according to RECIST 1.1. * Eastern cooperative oncology group (ECOG) performance status of 0 or 1 * Acceptable hematological status, liver and renal function as defined in the protocol * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Significant cardiac or peripheral vascular arterial disease * Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months) * Severe chronic obstructive or other pulmonary disease with hypoxemia * Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy * Subjects receiving concomitant treatment with radiotherapy or other investigational drugs * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects Experiencing Dose Limiting Toxicity (DLT) | Up to Day 28 of Cycle 1 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria | Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment |
| Duration of Overall Response According to RECIST Version 1.1 Criteria | Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment |
| Progression Free Survival (PFS) Time | Time from enrollment to progressive disease (PD) or occurrence of death due to any cause within 120 days of either first administration of study drug or the last tumor assessment |
| Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria | Baseline and 8 weeks after Day 1 of Cycle 1 |
| Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 30 after the last dose of study treatment |
| Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria | Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TH-302 Plus Nab-paclitaxel Plus Gemcitabine TH-302: TH-302 will be administered at a dose ranging from 170-340 milligram per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Nab-paclitaxel: Nab-paclitaxel will be administered at a dose ranging from 100-125 mg/m\^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose ranging from 800-1000 mg/m\^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | TH-302 Plus Nab-paclitaxel Plus Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 19 |
| serious Total, serious adverse events | 19 / 19 |
Outcome results
Primary
Number of Subjects Experiencing Dose Limiting Toxicity (DLT)
Time frame: Up to Day 28 of Cycle 1
Population: One patient not evaluable as they did not complete cycle 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TH-302 Plus Nab-paclitaxel Plus Gemcitabine | Number of Subjects Experiencing Dose Limiting Toxicity (DLT) | 1 Participants |
Secondary
Duration of Overall Response According to RECIST Version 1.1 Criteria
Time frame: Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Secondary
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 30 after the last dose of study treatment
Secondary
Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria
Time frame: Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Secondary
Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria
Time frame: Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Secondary
Progression Free Survival (PFS) Time
Time frame: Time from enrollment to progressive disease (PD) or occurrence of death due to any cause within 120 days of either first administration of study drug or the last tumor assessment
Secondary
Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria
Time frame: Baseline and 8 weeks after Day 1 of Cycle 1