QUILT-2.001: ALT-803 in Patients With Advanced Pancreatic Cancer in Conjunction With Gemcitabine and Nab-Paclitaxel
Study Details
Study Description
Brief Summary
This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer in conjunction with gemcitabine and nab-paclitaxel.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
The purpose of this study is to evaluate the safety and tolerability of escalating doses, to identify the Maximum Tolerated Dose (MTD) and designate a dose level for Phase II study (RP2D) of ALT-803 administered in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.
To access the anti-tumor activity of ALT-803 administered in combination with gemcitabine and nab-paclitaxel as measured by objective response rate, overall survival, progression-free survival, time to progression, and duration of response in patients with advanced pancreatic cancer.
To Characterize the pharmacokinetic, immunogenicity, and serum cytokine profile of ALT-803 in combination with gemcitabine and nab-paclitaxel in treated patients. To correlate circulating cell free DNA and circulating tumor DNA with clinical outcomes of the study in treated patients.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase Ib/II ALT-803 w/ gemcitabine and nab-paclitaxel
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Biological: Gemcitabine
Intravenous Infusion; Patients will receive two 4-week treatment cycles consisting of gemcitabine given on Day 1, 8, 15, 29, 36, and 43. Eligible patients may receive up to 10 additional treatment cycles.
Other Names:
Biological: Nab-paclitaxel
Intravenous Infusion; Patients will receive two 4-week treatment cycles consisting of nab-paclitaxel given on Day 1, 8, 15, 29, 36, and 43. Eligible patients may receive up to 10 additional treatment cycles.
Other Names:
Biological: ALT-803
Subcutaneous Injection; Patients will receive two 4-week cycles consisting of ALT-803 given on Day 2, 9, 16, 30, 37, and 44. Eligible patients may receive up to 10 additional treatment cycles.
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Outcome Measures
Primary Outcome Measures
- Determination of MTD; Phase Ib [9 Months]
Determine the maximum tolerated dose (MTD) level and designate the recommended dose level for phase II.
- Safety Profile (Number and severity of treatment related AEs); Phase Ib and II [48 Months]
Number and severity of treatment related adverse events (AEs) that occur or worsen after the first dose of study treatment
- Overall Survival; Phase II [8.5 Months]
Determine the 8.5 month overall survival of treated patients
Secondary Outcome Measures
- Objective response rate [72 Months]
Evaluate objective response rate in treated patients.
- Duration of response [72 Months]
Evaluate duration of response in treated patients.
- Time to progression [72 Months]
Evaluate time to progression in treated patients.
- Progression-free survival [72 Months]
Evaluate progression-free survival in treated patients.
- Biomarkers; Phase Ib [36 Months]
Measure the serum levels of the following including but not limited to Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Interferon-gamma (IFN-ɣ), Tumor necrosis factor-alpha (TNF-α) and Monocyte chemoattractant protein-1 (MCP-1)
- Determine the level of anti-ALT-803 antibodies in patient serum [36 Months]
Determine the level of anti-ALT-803 antibodies in patient serum
- Area under the plasma concentration-time curve from time zero to infinity (AUC); Phase Ib [36 Months]
Area under the plasma concentration-time curve from time zero to infinity (AUC)
- Correlation between the level of circulating cell free DNA in patient plasma and response to study treatment [36 Months]
Correlation between the level of circulating cell free DNA in patient plasma and response to study treatment
- Correlation between the level of tumor DNA in patient plasma and response to study treatment [36 Months]
Correlation between the level of tumor DNA in patient plasma and response to study treatment
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
Inclusion Criteria:
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Histologically or cytologically confirmed diagnosis of pancreatic cancer.
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For dose escalation phase (Phase Ib) distant metastatic disease or unresectable disease and not a candidate for down staging to resection.
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For expansion phase (Phase II) distant metastatic disease only.
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For dose escalation phase (Phase Ib) 0 or 1 prior lines of chemotherapy for advanced pancreatic cancer. Prior gemcitabine is allowed, however prior nab-paclitaxel is not allowed.
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For expansion phase (Phase II) no prior therapy for pancreatic cancer is allowed except for adjuvant therapy as long as it was completed ≥ 6 months prior to study treatment start
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Have at least one untreated and progressing tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor
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Prior radiation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Radiation therapy must have been completed at least 4 weeks prior to the baseline scan
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Resolved acute effects of any prior therapy to baseline or Grade ≤1
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The Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
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Life expectancy ≥12 weeks
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Glomerular Filtration Rate (GFR) > 40mL (milliliter)/min; Creatinine ≤ 1.5 x ULN (Upper limit of Normal)
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Platelets ≥100,000/uL (microliter)
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Hemoglobin ≥ 9g/dL
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Absolute Lymphocytes ≥800/uL
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Absolute neutrophil count/absolute granulocyte count ≥1500/uL
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Total bilirubin ≤ 2.0 X ULN, or ≤ 3.0 X ULN (for patients with Gilbert's Syndrome)
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aspartate aminotransferase, alanine aminotransferase ≤ 2.5 X ULN, or ≤ 5.0 X ULN (if liver metastasis present)
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Normal clinical assessment of pulmonary function
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Negative serum pregnancy test if female and of childbearing potential
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Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
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Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
Exclusion Criteria:
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No women who are pregnant or nursing
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No known hypersensitivity to gemcitabine or nab-paclitaxel
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No concurrent herbal or unconventional therapy
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No prior therapy with IL-15 or IL-15 analog
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No ongoing toxicity from prior anti-cancer treatment that may interfere with study treatment. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 or baseline before administration of the study treatment.
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No positive Hep C serology or active Hep B infection
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No congestive heart failure < 6 months
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No unstable angina pectoris < 6 months
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No myocardial infarction < 6 months
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No history of ventricular arrhythmias or severe cardiac dysfunction
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No history of uncontrollable supraventricular arrhythmias
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No New York Heart Association Class > II congestive heart failure
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No marked baseline prolongation of QT/QTc interval
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No known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
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No known prior organ allograft or allogeneic transplantation
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No known HIV-positive or AIDS unless patient is on a stable highly active antiretroviral therapy (HAART) regimen, have CD4 (cluster of differentiation 4) counts
350, with no detectable viral load on quantitative polymerase chain reaction test
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No untreated central nervous system metastases, or if treated must be neurologically stable for at least 2 weeks prior to enrollment
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No corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
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No psychiatric illness/social situation that would limit compliance
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No other illness that in the opinion of the investigator would exclude the subject from participating in the study
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No active systemic infection requiring parenteral antibiotic therapy
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No anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start
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No disease requiring systemic immunosuppressive therapy
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No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 3 years after surgical treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University of Hawaii Cancer Center | Honolulu | Hawaii | United States | 96813 |
Sponsors and Collaborators
- Altor BioScience
Investigators
- Study Chair: Hing C. Wong, Ph.D., Altor BioScience
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CA-ALT-803-01-15