Pancreatic Cancer
Conditions
Keywords
Cancer, Advanced Pancreatic Cancer
Brief summary
This is a Phase 2 multicenter, open-label, non-randomized study to examine the safety and effectiveness of BPM31510 administered over 144-hours (two 72-hour 110mg/Kg doses) continuous intravenous (IV) infusion in combination with gemcitabine in advanced pancreatic cancer patients as 2nd / 3rd line therapy. The study will enroll up to 25 patients in the US and Europe.
Detailed description
This is a Phase 2 multicenter, open-label, non-randomized study to examine the safety and effectiveness of BPM31510 administered over 144-hours (two 72-hour 110mg/Kg doses) continuous intravenous (IV) infusion in combination with gemcitabine in advanced pancreatic cancer patients as 2nd / 3rd line therapy. Cycle 1 of therapy is 6 weeks in duration with BPM31510 administered twice weekly on Tuesdays and Fridays for 6 weeks plus gemcitabine administered on Mondays, Days 21, 28 and 35. Cycles 2-12 are 4 weeks in duration with BPM31510 administered twice weekly on Tuesdays and Fridays for 4 weeks plus gemcitabine administered on Mondays, Days 7, 14 and 21. Response will be assessed after Cycle 2 (10 weeks) and patients who continue onto Cycles 2-12 will be assessed every 2 cycles (8 weeks). Patients will continue BPM31510 in combination with gemcitabine, for a maximum of 12 cycles in the absence of intolerable toxicity and progression. If gemcitabine is discontinued due to chemotherapy-related toxicity, patients may continue to receive BPM31510 as monotherapy. Patients who experience disease progression but are, in the opinion of the investigator, receiving clinical benefit may continue BPM31510 as a monotherapy or in combination with gemcitabine or as a monotherapy pending approval from the Sponsor.
Interventions
DRUGBPM31510 Nanosuspension Injection
DRUGGemcitabine
Sponsors
BPGbio
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Phase 2 multicenter, open-label, non-randomized to examine safety, effectiveness of combination of BPM31510 administered as 144-hour continuous intravenous (IV) infusion with gemcitabine in advanced pancreatic cancer patients as 2nd line therapy. Cycle 1 combination 6 weeks in duration for patients with BPM31510 administered twice wk. for 6 wk. and gemcitabine administered Days 21, 28 and 35. Cycles 2-12 are 4 wk. in duration with BPM31510 administered twice wk. for 4 wk. and gemcitabine administered Days 7, 14 and 21.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient has a histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. * The patient has undergone at least one prior, but no more than 2 prior standard, therapies for pancreatic cancer.If the patient has had prior gemcitabine treatment, the last date of gemcitabine administration-should be \> 3 months prior to screening for the study. All patients who have previously received gemcitabine should be discussed with the medical monitor during screening * The patient is at least 18 years old. * The patient has an Eastern Cooperative Oncology Group (ECOG) performance status * Measurable tumor lesions according to RECIST 1.1 criteria (Section 10.2). * In the opinion of the Investigator, the patient has a life expectancy of \> 3 months. * Sexually active patients and their partners agree to use an accepted method of contraception during the course of the study (Appendix C:Guidelines Regarding Women of Childbearing Potential). * Female patients of childbearing potential must have a negative pregnancy test within 1 week prior to beginning study treatment. * The patient has adequate organ and marrow function as follows: * absolute Neutrophil Count (ANC) ≥ 1500 mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL, * serum creatinine \< upper limit of normal (ULN); * total bilirubin \< 1.5 X (ULN) ; alanine aminotransferase (ALT), aspartate transaminase (AST) ≤ 2.5 times the upper limit of normal (ULN) if no liver involvement or ≤ 5 times the upper limit of normal with liver involvement. * The patient has serum electrolytes (including calcium, magnesium, phosphorous, sodium and potassium) within normal limits (supplementation to maintain normal electrolytes is allowed). * The patient has adequate coagulation: prothrombin time (PT) and an International Normalized Ratio (INR), and partial thromboplastin time (PTT) ≤ 1.5 times the upper limit of normal (ULN), * In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and has signed the informed consent document.
Exclusion criteria
* The patient has uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * The patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV). * The patient has received chemotherapy or radiotherapy within 4 weeks or has received nitrosoureas or mitomycin C within 6 weeks prior to the first dose of study drug. * The patient has received radiation to ≥ 25% of his or her bone marrow within 4 weeks of the first dose of study drug. * The patient has received an investigational drug within 30 days of the first dose of study drug. * Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). * History of other malignancies (except adequately treated Stage 1 cancer, cured basal cell carcinoma, superficial bladder cancer, Breast ductal carcinoma in situ (DCIS), or carcinoma in situ of the cervix) unless documented free of cancer for ≥5 years. * The patient has not recovered to grade ≤ 1 from adverse events (AEs) due to investigational drugs or other medications, which were administered more than 4 weeks prior to the first dose of study drug. * The patient is pregnant or lactating. * The patient is known to be positive for the human immunodeficiency virus (HIV). The effect of BPM31510 on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study. * The patient has an inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator or designee. * The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids. * The patient has uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding. * The patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition. * The patient requires therapeutic doses of any anticoagulant, including low molecular weight heparin (LMWH). Concomitant use of warfarin, even at prophylactic doses, is prohibited.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response | 10 weeks (End of Cycle 2) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. (the appearance of new lesions is also considered progression); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR) = CR + PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to study completion, an average of 1 year | The number of months from the first dose of study drug to the first documentation of progression or death due to any cause. |
| Overall Survival (OS) | Up to study completion, an average of 1 year | Overall Survival is defined as the number of months from the first dose of study drug to the date of death due to any cause. |
| Time to Progression (TTP) | Day 1, End of Cycle 2 (10 weeks) and every 2 cycles (every 8 weeks) through study completion, an average of 1 year | Time to Progression is defined as tumor progression measured from the first dose of study drug to the first documentation of progression. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BPM31510 Monotherapy BPM31510 IV nanosuspension injection (40mg/mL) was administered over 144 hours (two 72-hour 110 mg/Kg doses per week). Each patient received 2 consecutive 72-hour infusions per week (Tuesday-Friday and Friday-Monday). | 17 |
| BPM31510 Plus Gemcitabine BPM31510 Nanosuspension Injection (40 mg/mL) will be administered IV over 144 hours at the starting dose of 110 mg/kg. Each patient will receive 2 consecutive 72-hour infusions per week (Tuesday-Friday and Friday-Monday). The patient will be subsequently treated with gemcitabine IV once weekly at a starting dose of 1000 mg/m2.
Cycle 1 of combination therapy is 6 weeks in duration for patients with BPM31510 administered twice weekly on Tuesdays and Fridays for 6 weeks and gemcitabine administered on Mondays, Days 21, 28 and 35. Cycles 2-12 are 4 weeks in duration with BPM31510 administered twice weekly on Tuesdays and Fridays for 4 weeks and gemcitabine administered on Mondays, Days 7, 14 and 21.
BPM31510 Nanosuspension Injection
Gemcitabine | 28 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Progressive Disease | 7 | 10 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Symptomatic deterioration | 5 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 4 |
Baseline characteristics
| Characteristic | BPM31510 Plus Gemcitabine | Total | BPM31510 Monotherapy |
|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 9.5 | 63.3 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 10.9 |
| Age, Customized 60 - 69 years | 16 participants | 21 participants | 4 participants |
| Age, Customized < 60 years | 5 participants | 11 participants | 7 participants |
| Age, Customized >= 70 years | 7 participants | 16 participants | 6 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 38 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| 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 | 2 Participants | 2 Participants | 0 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 25 Participants | 41 Participants | 16 Participants |
| Sex: Female, Male Female | 9 Participants | 17 Participants | 8 Participants |
| Sex: Female, Male Male | 19 Participants | 28 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 28 / 28 | 17 / 17 |
| other Total, other adverse events | 28 / 28 | 16 / 17 |
| serious Total, serious adverse events | 12 / 28 | 10 / 17 |
Outcome results
Primary
Treatment Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. (the appearance of new lesions is also considered progression); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR) = CR + PR
Time frame: 10 weeks (End of Cycle 2)
Population: Adequately Treated Analysis Set (ATAS) - defined as all the patients who met the inclusion/exclusion criteria, completed at least the first two cycles of therapy with a total of at least 18 days of drug infusion during Cycle 1 and at least 12 days of drug infusion during Cycle 2, and had an initial evaluation of response following the end of the second cycle such that an overall response was considered evaluable based on RECIST 1.1 criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BPM31510 Monotherapy | Treatment Response | Overall Response | 0 participants |
| BPM31510 Monotherapy | Treatment Response | Complete Response | 0 participants |
| BPM31510 Monotherapy | Treatment Response | Partial Response | 0 participants |
| BPM31510 Monotherapy | Treatment Response | Progressive Disease | 2 participants |
| BPM31510 Monotherapy | Treatment Response | Stable disease | 1 participants |
| BPM31510 Plus Gemcitabine | Treatment Response | Stable disease | 8 participants |
| BPM31510 Plus Gemcitabine | Treatment Response | Progressive Disease | 8 participants |
| BPM31510 Plus Gemcitabine | Treatment Response | Complete Response | 0 participants |
| BPM31510 Plus Gemcitabine | Treatment Response | Overall Response | 0 participants |
| BPM31510 Plus Gemcitabine | Treatment Response | Partial Response | 0 participants |
Secondary
Overall Survival (OS)
Overall Survival is defined as the number of months from the first dose of study drug to the date of death due to any cause.
Time frame: Up to study completion, an average of 1 year
Population: Adequately Treated Analysis Set (ATAS) - defined as all the patients who met the inclusion/exclusion criteria, completed at least the first two cycles of therapy with a total of at least 18 days of drug infusion during Cycle 1 and at least 12 days of drug infusion during Cycle 2, and had an initial evaluation of response following the end of the second cycle such that an overall response was considered evaluable based on RECIST 1.1 criteria.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BPM31510 Monotherapy | Overall Survival (OS) | 7.4 Months |
| BPM31510 Plus Gemcitabine | Overall Survival (OS) | 7.3 Months |
Secondary
Progression Free Survival (PFS)
The number of months from the first dose of study drug to the first documentation of progression or death due to any cause.
Time frame: Up to study completion, an average of 1 year
Population: PFS is defined as the number of months from the first dose of study drug to the first documentation of progression or death due to any cause.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BPM31510 Monotherapy | Progression Free Survival (PFS) | 2.4 Months |
| BPM31510 Plus Gemcitabine | Progression Free Survival (PFS) | 4.0 Months |
Secondary
Time to Progression (TTP)
Time to Progression is defined as tumor progression measured from the first dose of study drug to the first documentation of progression.
Time frame: Day 1, End of Cycle 2 (10 weeks) and every 2 cycles (every 8 weeks) through study completion, an average of 1 year
Population: Adequately Treated Analysis Set (ATAS) - defined as all the patients who met the inclusion/exclusion criteria, completed at least the first two cycles of therapy with a total of at least 18 days of drug infusion during Cycle 1 and at least 12 days of drug infusion during Cycle 2, and had an initial evaluation of response following the end of the second cycle such that an overall response was considered evaluable based on RECIST 1.1 criteria.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BPM31510 Monotherapy | Time to Progression (TTP) | 2.4 Months |
| BPM31510 Plus Gemcitabine | Time to Progression (TTP) | 4.0 Months |