Advanced Solid Tumors
Conditions
Keywords
Advanced solid tumors, Unresectable, Metastatic, Limited treatment options, Measurable or nonmeasurable disease
Brief summary
The purpose of this study is to determine a safe dose of LY573636 (tasisulam) when used in 5 separate combinations with an approved cancer medication for treating participants with advanced cancer. Data from this study will be reviewed for any side effects or anti-tumor activity that may be associated with the LY573636 combination treatments.
Interventions
DRUGGemcitabine
1000 mg/m2 administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
DRUGDocetaxel
60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
DRUGTemozolomide
200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
DRUGCisplatin
75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
DRUGErlotinib
150 mg administered orally days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
DRUGLY573636
Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who have histologically confirmed solid malignancy or lymphoma that is unresectable and/or metastatic for which monotherapy with gemcitabine HCl, docetaxel, temozolomide, cisplatin, or erlotinib would otherwise be appropriate * Must have tumor progression after receiving standard/approved chemotherapy or limited treatment options * Must have measurable or nonmeasurable disease * Have given written informed consent prior to any study-specific procedures * Must have adequate hepatic, hematologic and renal function * Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Endocrine therapies for the treatment of prostate cancer may be continued, at the discretion of the investigator. Whole brain radiation must have been completed 90 days before starting study therapy. Participants without evidence of brain metastases who have received prophylactic whole brain irradiation as part of standard of care for small cell lung cancer may be included in the study with a shorter washout period pending approval by the Lilly physician. * Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug. * Females with child-bearing potential must have had a negative serum pregnancy test within 7 days prior to the first dose of study drug. * Must have a serum albumin level greater than or equal to 3.0 g/dL (30 g/L). * Must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
Exclusion criteria
* Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication * Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in the study * Participants with active central nervous system or brain metastasis at the time of study entry. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out brain metastasis. Participants with stable CNS metastasis not requiring steroids may be eligible. * Have a current hematologic malignancy (other than lymphoma) * Participants with serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study) * Participants actively receiving warfarin (Coumadin®) therapy * Participants who have previously completed or withdrawn from any study investigating LY573636 * Participants with a known hypersensitivity to one of the combination drugs cannot be enrolled to the treatment arm which includes that chemotherapeutic combination * Females who are pregnant or breast feeding * Have known positive test results of HIV, hepatitis B, or hepatitis C * Participants receiving amiodarone, quinidine, propofol, or clozapine. * Participants receiving treatment with strong or moderate inhibitors of CYP2C19, including proton-pump inhibitors (PPIs). Esomeprazole or pantoprazole are allowed if not administered 72 hours before or after LY573636 administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities Cycle 1 | Baseline to Cycle 1 (Up to Day 28) | A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade 4 neutropenia lasting more than 5 days. Grade 4 neutropenia with fever or Grade 4 thrombocytopenia, regardless of duration; Grade ≥3 thrombocytopenia with bleeding, regardless of duration; Grade ≥3 nonhematologic toxicity (excluding nausea/vomiting or diarrhea that can be controlled with medication, and alopecia). Grade 3 electrolyte toxicity (for example, hypokalemia, hypophosphatemia) will not be considered a DLT unless it is considered related to the study drug or combination and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK): Concentration Maximum (Cmax) | Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion. | Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion. |
| Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Baseline to Study Completion (Up to 2 years) | Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions. |
| Number of Participants With a Clinically Significant Effects | Baseline to Study Completion (Up to 2 years) | Clinically significant effects are reported if a Grade 3 or higher treatment emergent adverse event (TEAE) and observed in ≥10% of participants or a toxicity possibly related to study drug based on Common Terminology Criteria for Adverse Events (CTCAE). A summary of other nonserious AEs and all SAEs, regardless of causality is located in the Reported Adverse Event section. |
| PK: Area Under the Curve Albumin (AUCalb) | Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion. | Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion. |
Countries
United States
Participant flow
Pre-assignment details
Study completion was defined as when the recommended dose of LY573636 (tasisulam) was defined for each treatment arm or if a decision was made to stop enrollment in the study for business reasons.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. | 25 |
| Arm A Tasisulam + Gemcitabine Dose Confirmation Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. | 33 |
| Arm B* Tasisulam + Docetaxel Dose Escalation Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 5 |
| Arm B1 Tasisulam + Docetaxel Dose Escalation Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Tasisulam Day 4 of a 28 day cycle. Participant's may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. | 5 |
| Arm B2 Tasisulam + Docetaxel Dose Escalation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 24 |
| Arm B2 Tasisulam + Docetaxel Dose Confirmation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 26 |
| Arm C Tasisulam + Temozolomide Dose Escalation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met | 19 |
| Arm C Tasisulam + Temozolomide Dose Confirmation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 6 |
| Arm D* Tasisulam + Cisplatin Dose Escalation Tasisulam and 75 mg/m2 cisplatin administered IV on Day 1 in 21-day cycles. | 4 |
| Arm D Tasisulam + Cisplatin Dose Escalation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 14 |
| Arm D Tasisulam + Cisplatin Dose Confirmation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 45 |
| Arm E Tasisulam + Erlotinib Dose Escalation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 16 |
| Arm E Tasisulam + Erlotinib Dose Confirmation Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.
Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. | 12 |
| Total | 234 |
Baseline characteristics
| Characteristic | Total | Arm E Tasisulam + Erlotinib Dose Confirmation | Arm E Tasisulam + Erlotinib Dose Escalation | Arm D Tasisulam + Cisplatin Dose Confirmation | Arm D Tasisulam + Cisplatin Dose Escalation | Arm D* Tasisulam + Cisplatin Dose Escalation | Arm C Tasisulam + Temozolomide Dose Confirmation | Arm C Tasisulam + Temozolomide Dose Escalation | Arm B2 Tasisulam + Docetaxel Dose Confirmation | Arm B2 Tasisulam + Docetaxel Dose Escalation | Arm B1 Tasisulam + Docetaxel Dose Escalation | Arm B* Tasisulam + Docetaxel Dose Escalation | Arm A Tasisulam + Gemcitabine Dose Confirmation | Arm A Tasisulam + Gemcitabine Dose Escalation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.6 years | 61.63 years | 57.84 years | 67.36 years | 54.88 years | 48.46 years | 65.7 years | 63.3 years | 62.7 years | 64.2 years | 78.8 years | 66.3 years | 65.5 years | 63.2 years |
| Race/Ethnicity, Customized Race African | 22 Participants | 0 Participants | 3 Participants | 6 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Caucasian | 197 Participants | 11 Participants | 12 Participants | 36 Participants | 10 Participants | 3 Participants | 6 Participants | 17 Participants | 21 Participants | 22 Participants | 3 Participants | 3 Participants | 30 Participants | 23 Participants |
| Race/Ethnicity, Customized Race East Asian | 7 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Hispanic | 7 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race West Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 234 Participants | 12 Participants | 16 Participants | 45 Participants | 14 Participants | 4 Participants | 6 Participants | 19 Participants | 26 Participants | 24 Participants | 5 Participants | 5 Participants | 33 Participants | 25 Participants |
| Sex: Female, Male Female | 117 Participants | 7 Participants | 9 Participants | 21 Participants | 7 Participants | 3 Participants | 3 Participants | 4 Participants | 17 Participants | 10 Participants | 2 Participants | 3 Participants | 19 Participants | 12 Participants |
| Sex: Female, Male Male | 117 Participants | 5 Participants | 7 Participants | 24 Participants | 7 Participants | 1 Participants | 3 Participants | 15 Participants | 9 Participants | 14 Participants | 3 Participants | 2 Participants | 14 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 25 | 8 / 33 | 1 / 5 | 1 / 5 | 0 / 24 | 4 / 26 | 3 / 19 | 3 / 6 | 1 / 4 | 2 / 14 | 7 / 45 | 3 / 16 | 3 / 12 |
| other Total, other adverse events | 24 / 25 | 33 / 33 | 5 / 5 | 5 / 5 | 24 / 24 | 26 / 26 | 19 / 19 | 6 / 6 | 4 / 4 | 14 / 14 | 43 / 45 | 16 / 16 | 11 / 12 |
| serious Total, serious adverse events | 9 / 25 | 14 / 33 | 1 / 5 | 2 / 5 | 9 / 24 | 12 / 26 | 8 / 19 | 4 / 6 | 1 / 4 | 4 / 14 | 19 / 45 | 6 / 16 | 7 / 12 |
Outcome results
Primary
Number of Participants With Dose-Limiting Toxicities Cycle 1
A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade 4 neutropenia lasting more than 5 days. Grade 4 neutropenia with fever or Grade 4 thrombocytopenia, regardless of duration; Grade ≥3 thrombocytopenia with bleeding, regardless of duration; Grade ≥3 nonhematologic toxicity (excluding nausea/vomiting or diarrhea that can be controlled with medication, and alopecia). Grade 3 electrolyte toxicity (for example, hypokalemia, hypophosphatemia) will not be considered a DLT unless it is considered related to the study drug or combination and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section.
Time frame: Baseline to Cycle 1 (Up to Day 28)
Population: All participants who received at least one dose of study drug Tasisulam in dose escalation phase and experienced a dose-limiting toxicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 4 Participants |
| Arm A Tasisulam + Gemcitabine Dose Confirmation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 0 Participants |
| Arm B* Tasisulam + Docetaxel Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 4 Participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 4 Participants |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 3 Participants |
| Arm B2 Tasisulam + Docetaxel Dose Confirmation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 0 Participants |
| Arm C Tasisulam + Temozolomide Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 3 Participants |
| Arm C Tasisulam + Temozolomide Dose Confirmation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 0 Participants |
| Arm D* Tasisulam + Cisplatin Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 0 Participants |
| Arm D Tasisulam + Cisplatin Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 2 Participants |
| Arm D Tasisulam + Cisplatin Dose Confirmation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 0 Participants |
| Arm E Tasisulam + Erlotinib Dose Escalation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 1 Participants |
| Arm E Tasisulam + Erlotinib Dose Confirmation | Number of Participants With Dose-Limiting Toxicities Cycle 1 | 0 Participants |
Secondary
Number of Participants With a Clinically Significant Effects
Clinically significant effects are reported if a Grade 3 or higher treatment emergent adverse event (TEAE) and observed in ≥10% of participants or a toxicity possibly related to study drug based on Common Terminology Criteria for Adverse Events (CTCAE). A summary of other nonserious AEs and all SAEs, regardless of causality is located in the Reported Adverse Event section.
Time frame: Baseline to Study Completion (Up to 2 years)
Population: All participants who received at least one dose of study drug Tasisulam and experienced a Grade 3 or higher TEAE or drug toxicity possibly related to study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 15 Participants |
| Arm A Tasisulam + Gemcitabine Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 13 Participants |
| Arm A Tasisulam + Gemcitabine Dose Confirmation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 18 Participants |
| Arm A Tasisulam + Gemcitabine Dose Confirmation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 18 Participants |
| Arm B* Tasisulam + Docetaxel Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 0 Participants |
| Arm B* Tasisulam + Docetaxel Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 5 Participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 0 Participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 4 Participants |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 16 Participants |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 18 Participants |
| Arm B2 Tasisulam + Docetaxel Dose Confirmation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 26 Participants |
| Arm B2 Tasisulam + Docetaxel Dose Confirmation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 19 Participants |
| Arm C Tasisulam + Temozolomide Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 13 Participants |
| Arm C Tasisulam + Temozolomide Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 11 Participants |
| Arm C Tasisulam + Temozolomide Dose Confirmation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 6 Participants |
| Arm C Tasisulam + Temozolomide Dose Confirmation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 6 Participants |
| Arm D* Tasisulam + Cisplatin Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 0 Participants |
| Arm D* Tasisulam + Cisplatin Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 1 Participants |
| Arm D Tasisulam + Cisplatin Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 8 Participants |
| Arm D Tasisulam + Cisplatin Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 7 Participants |
| Arm D Tasisulam + Cisplatin Dose Confirmation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 30 Participants |
| Arm D Tasisulam + Cisplatin Dose Confirmation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 30 Participants |
| Arm E Tasisulam + Erlotinib Dose Escalation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 5 Participants |
| Arm E Tasisulam + Erlotinib Dose Escalation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 5 Participants |
| Arm E Tasisulam + Erlotinib Dose Confirmation | Number of Participants With a Clinically Significant Effects | TEAE >/= Grade 3 | 7 Participants |
| Arm E Tasisulam + Erlotinib Dose Confirmation | Number of Participants With a Clinically Significant Effects | Toxicity >/= Grade 3 | 7 Participants |
Secondary
Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)
Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions.
Time frame: Baseline to Study Completion (Up to 2 years)
Population: All participants who received study drug Tasisulam and had CR or PR tumor response at dose confirmation phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Non-Small Cell Lung Cancer (NSCLC) | 0.0 percentage of participants |
| Arm A Tasisulam + Gemcitabine Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Pancreas | 13.3 percentage of participants |
| Arm A Tasisulam + Gemcitabine Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Other | 14.3 percentage of participants |
| Arm A Tasisulam + Gemcitabine Dose Confirmation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Other | 6.3 percentage of participants |
| Arm A Tasisulam + Gemcitabine Dose Confirmation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Non-Small Cell Lung Cancer (NSCLC) | 20.0 percentage of participants |
| Arm B* Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Other | 0.0 percentage of participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Non-Small Cell Lung Cancer (NSCLC) | 5.0 percentage of participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Other | 10.0 percentage of participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Pancreas | 0 percentage of participants |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Small Cell Lung Cancer (SCLC) | 7.1 percentage of participants |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Pancreas | 0.0 percentage of participants |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Other | 14.3 percentage of participants |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) | Non-Small Cell Lung Cancer (NSCLC) | 0.0 percentage of participants |
Secondary
Pharmacokinetic (PK): Concentration Maximum (Cmax)
Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Time frame: Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Population: All participants who received at least one dose of study drug Tasisulam and had evaluable PK data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation | Pharmacokinetic (PK): Concentration Maximum (Cmax) | Cycle 1 | 306 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 20.03 |
| Arm A Tasisulam + Gemcitabine Dose Escalation | Pharmacokinetic (PK): Concentration Maximum (Cmax) | Cycle 2 | 250 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 31.39 |
Secondary
PK: Area Under the Curve Albumin (AUCalb)
Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Time frame: Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Population: All participants who received at least one dose of study drug Tasisulam and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation | PK: Area Under the Curve Albumin (AUCalb) | Cycle 1 | 946 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 427.2 |
| Arm A Tasisulam + Gemcitabine Dose Escalation | PK: Area Under the Curve Albumin (AUCalb) | Cycle 2 | 648 micrograms*hour/milliliter (µg*h/mL) | Geometric Coefficient of Variation 765.92 |