PEN-866 in Patients With Advanced Solid Malignancies
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|ClinicalTrials.gov Identifier: NCT03221400|
Recruitment Status : Recruiting
First Posted : July 18, 2017
Last Update Posted : April 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma Sarcoma Rhabdomyosarcoma Neoplasms Small Cell Lung Cancer Triple Negative Breast Cancer Adenocarcinoma of the Pancreas Colorectal Carcinoma Gastric Adenocarcinoma Advanced Cancer Solid Tumor Solid Carcinoma||Drug: PEN-866||Phase 1 Phase 2|
Phase 1 will employ an adaptive model guided with overdose control principle to make dose recommendations and estimate the maximum tolerated dose (MTD).
Phase 2a begins once all patients treated in Phase 1 have been assessed for safety and the Safety Review Committee (SRC) has reviewed all safety data and recommends continuing with Phase 2a. PEN-866 will be evaluated using the recommended Phase 2 dose identified by the SRC at the conclusion of Phase 1 based on the safety, tolerability, pharmacokinetic, and pharmacodynamics profile of PEN-866 during Phase 1.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2a, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Activity of PEN-866 in Patients With Advanced Solid Malignancies|
|Actual Study Start Date :||August 29, 2017|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||June 2020|
Intravenous administration of PEN-866
PEN-866 is a miniaturized conjugate that comprises an HSP90 targeting ligand linked to SN-38, the active metabolite of irinotecan. PEN-866 is available as a sterile lyophilized powder for solution for infusion.
- Incidence of Dose-Limiting Toxicities (DLTs) [ Time Frame: Patients will be followed for 28 days in Cycle 1 to determine the incidence of DLTs. ]In Phase 1, the Maximum Tolerated Dose (MTD) will be determined by assessing the incidence of DLTs and treatment related adverse events.
- Incidence of treatment related adverse events [ Time Frame: up to 28 days following the last treatment. ]In Phase 1, safety and tolerability will be determined by assessing the incidence of treatment related adverse events.
- Objective response rate (ORR) of tumors using RECIST 1.1 criteria [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to 18 months ]
In Phase 2, for each of the 6 tumor-specific cohorts, ORR will be estimated and presented with 95% confidence intervals based on the exact binomial distribution.
In addition, for each tumor-specific cohort, a Bayesian approach will be used to estimate the ORR and its 95% credible interval based on the posterior distribution. At completion of the study, within each tumor-specific cohort, the prior distribution will be updated with all data available from the evaluable patients at the MTD to obtain the posterior distribution of the true ORR.
- Maximum concentration of PEN-866 and its metabolites (Cmax) [ Time Frame: 1 Month ]Characterize the pharmacokinetic properties of PEN-866
- Area under the curve (AUC) of PEN-866 and its metabolites [ Time Frame: 1 Month ]Characterize the pharmacokinetic properties of PEN-866
- Half-life (t1/2) of PEN-866 and its metabolites [ Time Frame: 1 Month ]Characterize the pharmacokinetic properties of PEN-866
- Tumor response using RECIST criteria [ Time Frame: 2 Months ]In Phase 1, size of tumors by CT or MRI (RECIST)
- Radiographic progression free survival [ Time Frame: From date of first treatment/trial entry until the date of first documented progression or date of death from any cause, whichever is first, assessed up to 18 months ]In Phase 2, size of tumors by CT or MRI (RECIST)
- Overall survival [ Time Frame: From date of first treatment/trial entry until the date of date of death from any cause, assessed up to 18 months ]In Phase 2, time to death
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03221400
|Contact: Tarveda Clinical Information Center||(617) email@example.com|
|United States, Colorado|
|Sarah Cannon Reasearch Institute at HealthONE||Recruiting|
|Denver, Colorado, United States, 80218|
|United States, Maryland|
|National Institutes of Health / National Cancer Institute||Recruiting|
|Bethesda, Maryland, United States, 20892|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Anish Thomas, MD||National Cancer Institute (NCI)|