Phase 1 Open-label Two-stage Safety and Tolerability Study With Subcutaneous Administration of Andes-1537 for Injection in Patients With Specific Types of Advanced Solid Tumors That Are Refractory To or No Available Standard Therapy
Overview
- Phase
- Phase 1
- Intervention
- Andes-1537 for Injection
- Conditions
- Tumor, Solid
- Sponsor
- Andes Biotechnologies
- Enrollment
- 67
- Locations
- 4
- Primary Endpoint
- Incidence of treatment-emergent adverse events (TEAEs) through stages 1 and 2 of the study
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The study is a Phase 1 Open-label Two-stage, Safety and Tolerability Study with Cancer Type-specific Cohorts, Evaluating Subcutaneous Administration of Andes-1537 for Injection in Patients with Advanced Solid Tumors that are Refractory to Standard Therapy or For Which No Standard Therapy Is Available. Patients with unresectable solid tumors that are refractory or have failed standard therapy and are deemed non-eligible or intolerant to further therapy or for which no standard therapy is available will be included in 5 cancer type-specific parallel cohorts. The following tumor types will be evaluated for potential inclusion in each cancer type-specific cohort: gallbladder & biliary tract carcinoma; cervical carcinoma; gastric carcinoma; pancreatic carcinoma, and colorectal carcinoma.
Detailed Description
After screening, 9 patients in each cancer type-specific cohort (gallbladder \& biliary tract carcinoma; cervical carcinoma; gastric carcinoma; pancreatic carcinoma, and colorectal carcinoma) will enter stage 1. These patients will receive a dose of 400 mg of Andes-1537 five times per week for continuous cycles of 4 weeks that will be repeated until the patients presents drug toxicity requiring treatment discontinuation or disease progression with no noted clinical benefit as assessed by the investigator. The safety and tolerability evaluation will be continuous during the study. The efficacy evaluation will be done by analysis of the clinical objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after patients complete the first two cycles (8 weeks). Thereafter, clinical ORR will be assessed every 8 weeks. Additionally, tumor-cell activity assessment will be performed in biopsy samples after the patients complete the first 2 cycles (8 weeks). Tumor markers assessment according to the type of tumor will be evaluated every 2 cycles and at the end of study (EOS) visit. Analysis of the tumor metabolic activity through the PET-CT scan and quality of life of patients through questionnaire will be evaluated every 2 cycles. As predefined and according with the decision of the Study Safety and Steering Committee (SSC), in those cohorts where minimal clinical response criteria were met or according to the decision of the SSC based on the risk / benefit analysis, considering toxicity criteria and observed biological responses, 15 additional patients will be recruited (total of 24 patients per cohort) for stage 2 of the study. Patients included in stage 2 will receive the same treatment regimen described for stage 1 and will be followed until the patients present disease progression or drug toxicity requiring treatment discontinuation. Patients included in stage 2 will receive the same follow-up as patients in stage 1.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women 18 years of age or older.
- •Can understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessment or procedure, and are able to adhere to the study visit schedule and other protocol requirements.
- •Patients with documented pathological evidence of advanced unresectable solid tumors that are, in the opinion of their treating physician, refractory or have failed standard therapy and are deemed non-eligible or intolerant to further therapy, or for which no standard therapy is available will be enrolled in both stages of the study in the following 4 cancer type-specific cohorts:
- •Gallbladder \& Biliary Tract Cancer: Histologically confirmed stage 4 or unresectable stage 3b biliary tract \& gallbladder adenocarcinoma with relapsed, refractory or progressive disease, who cannot tolerate or is considered resistant to platinum based chemotherapy for advanced disease such as cis-platinum and gemcitabine.
- •Cervical Cancer: Histologically confirmed stages 4 or 3b cervical cancer with relapsed, refractory or progressive disease, who cannot tolerate or is considered resistant to platinum based chemotherapy for advanced disease such as cis-platinum/carboplatin and paclitaxel.
- •Gastric Cancer: Histologically confirmed stage 4 or recurrent gastric adenocarcinoma with relapsed, refractory or progressive disease, who cannot tolerate or has progressed after first and second line combined chemotherapy regimens containing Epirubicin, cisplatin, fluorouracil (5-FU)/ leucovorin, oxaliplatin, irinotecan and/or docetaxel. Patients with Her2Neu positive cancer will not be eligible.
- •Pancreatic Cancer: Histologically confirmed stage 4 or recurrent pancreatic adenocarcinoma with relapsed, refractory or progressive disease, who cannot tolerate or is considered resistant to combined treatment with leucovorin calcium, 5-FU, irinotecan and oxaliplatin (FOLFIRINOX) or Gemcitabine based chemotherapy, depending on age and performance status.
- •Colorectal Cancer: Histologically confirmed Stage IV colorectal adenocarcinoma with relapsed, refractory, or progressive disease, who cannot tolerate or is considered resistant to combined treatment with fluoropyrimidines and/or oxaliplatin and/or irinotecan and/or Epidermal Growth Factor-1 (EGF1) inhibitors (depending on molecular profile) either as single agent or in combination therapy, depending treating oncologist´s decision. Patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) - Neuroblastoma RAS Viral Oncogene Homolog (NRAS) wild type should have progressed after cetuximab or panitunumab unless contraindicated or not available.
- •Have measurable disease by RECIST.
- •Have Eastern Cooperative Oncology Group (ECOG) performance status of ≥
Exclusion Criteria
- •Have known central nervous system metastases.
- •Have unstable angina, clinically significant cardiac arrhythmia, New York Heart Association Class 3 or 4 congestive heart failure, or prolonged QT interval corrected (QTc) wave of greater than 470 ms.
- •Receiving treatment with any medication known to produce QT prolongation within 7 days of study entry.
- •Have had prior systemic chemotherapy treatments or investigational modalities ≤ 5 half-lives (t1/2) or 4 weeks, whichever is shorter, prior to starting treatment with Andes 1537 or who have not recovered from side effects, grade 2 or greater, of such therapy (except alopecia).
- •Have had major surgery ≤ 2 weeks prior to starting treatment with Andes-1537 or who have not recovered from side effects of such surgery.
- •Are pregnant or breastfeeding.
- •Have had deep vein thrombosis (DVT) or venous thromboembolism within 6 weeks of study entry. Patients are permitted to enter the study if they are receiving anticoagulation therapy considered to be in the therapeutic range and are stable for ≥ 4 weeks prior to study entry.
- •Have active uncontrolled bleeding or a known bleeding disorder.
- •Have any serious or unstable concomitant systemic conditions that are incompatible with this clinical study, including but not limited to substance abuse, psychiatric disturbance, or uncontrolled intercurrent illness (including active infection), arterial thrombosis, or symptomatic pulmonary embolism.
- •Have a known sensitivity to any of the components of Andes-
Arms & Interventions
Andes-1537
There will be 5 different cohorts each representing a different type of solid cancer (gallbladder and biliary tract cancer, cervical cancer, gastric cancer, pancreatic cancer, and colorectal cancer). All patients will receive a dose of 400 mg of Andes-1537 five days per week for continuous cycles of 4 weeks that will be repeated until the patients presents drug toxicity requiring treatment discontinuation or disease progression without any noted clinical benefit as assessed by the investigator.
Intervention: Andes-1537 for Injection
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events (TEAEs) through stages 1 and 2 of the study
Time Frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
Assessment of safety and tolerability through the incidence and severity of TEAEs from change in baseline for reported adverse events, safety labs, vital signs, electrocardiograms, and injection site reactions
Secondary Outcomes
- Duration of response and duration of stable disease according to RECIST(Assessment performed every 8 weeks following completion of 2 treatment cycles (each cycle 4 weeks) from screening to study completion until confirmed disease progression or Andes-1537 toxicity (approximately 24 weeks or earlier if patient discontinues))
- Progression free survival time according to RECIST(Assessment performed every 8 weeks following completion of 2 treatment cycles (each cycle 4 weeks) from screening to study completion until confirmed disease progression or Andes-1537 toxicity (approximately 24 weeks or earlier if patient discontinues))
- Andes-1537 tumor-cell biomarker activity in biopsy tissue(Screening to end of cycle 2 (each cycle 4 weeks) treatment (approximately 8 weeks))
- Plasma concentration of Andes-1537 after subcutaneous administration for pharmacokinetic (PK) parameter area under the plasma concentration versus time (AUC)(Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study))
- Plasma concentration of Andes-1537 after subcutaneous administration for PK parameter maximum plasma concentration (Cmax)(Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study))
- Plasma concentration of Andes-1537 after subcutaneous administration for PK parameter time to maximum concentration (Tmax)(Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study))
- Plasma concentration of Andes-1537 after subcutaneous administration for PK parameter half-life (t1/2)(Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study))
- Objective response rate (ORR) according to RECIST(Assessment performed every 8 weeks following completion of 2 treatment cycles (each cycle 4 weeks) from screening to study completion until confirmed disease progression or Andes-1537 toxicity (approximately 24 weeks or earlier if patient discontinues))
- Incidence of Andes-1537 anti-drug antibodies (ADAs) in the plasma(Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study))