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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 : November 20, 2018
Sponsor:
Information provided by (Responsible Party):
Tarveda Therapeutics

Brief Summary:
Protocol PEN-866-001 is an open-label, multi-center, first-in-human Phase 1/2a study evaluating PEN-866 in patients with advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

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

Detailed Description:

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)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PEN-866
Intravenous administration of PEN-866
Drug: 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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Secondary Outcome Measures :
  1. Maximum concentration of PEN-866 and its metabolites (Cmax) [ Time Frame: 1 Month ]
    Characterize the pharmacokinetic properties of PEN-866

  2. Area under the curve (AUC) of PEN-866 and its metabolites [ Time Frame: 1 Month ]
    Characterize the pharmacokinetic properties of PEN-866

  3. Half-life (t1/2) of PEN-866 and its metabolites [ Time Frame: 1 Month ]
    Characterize the pharmacokinetic properties of PEN-866

  4. Tumor response using RECIST criteria [ Time Frame: 2 Months ]
    In Phase 1, size of tumors by CT or MRI (RECIST)

  5. 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)

  6. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • M/F at least 18 years old
  • Performance status 0 or 1
  • Adequate bone marrow, liver, and kidney function within 28 days prior to first dose
  • Serum potassium, calcium, magnesium, phosphorus within normal limits
  • Adequate birth control
  • Central venous access line is required
  • Patients in Phase 1 must also have confirmed advanced solid malignancy that has progressed after one or more prior lines of anticancer therapy and no other standard of care therapies that are deemed appropriate for treatment of their malignancy
  • Patients in Phase 2a must have confirmed diagnosis and specific disease history of Ewing sarcoma, or rhabdomyosarcoma, or small-cell lung cancer, or triple-negative breast cancer, or pancreatic adenocarcinoma, or colorectal cancer, or gastric adenocarcinoma
  • Patients in Phase 2a must have measurable disease per RECIST 1.1 and documented disease progression during or after their most recent line of anticancer therapy.

Exclusion Criteria:

  • Treatment with anticancer therapy or investigational drug or device within 2 wk (6 wk for nitrosureas or mitomycin C) or 5 half-lives of agent, whichever is shorter, prior to first drug dose, and any drug-related toxicities must have recovered to grade 1 or less
  • History within last 5 years of an invasive malignancy other than resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment
  • Cardiac disease such as unstable angina, myocardial infarction within 6 months of screening, NY Heart Association Class 1 or 2 heart failure, QTc greater than 470 msec, congenital long Qt syndrome, symptomatic orthostatic hypotension within 6 months of screening, uncontrolled hypertension, or clinically important abnormalities in heart rhythm, conduction, morphology of resting ECG
  • Stroke or transient ischemic attack within 6 months of screening
  • Peripheral neuropathy greater than grade 2
  • Patients requiring medications with drugs that are inhibitors of UGT1A1 or substrates of CYP1A2, P-gP, BCRP, OATP1B1, OATP1B3 or OCT1 transporters
  • History of leptomeningeal disease or spinal cord compression
  • Brain metastases unless asymptomatic and not requiring steroids for at least 4 weeks prior to start of study treatment
  • Major surgery within 28 days of first drug dose
  • Female pregnant or breast feeding
  • Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver transplant, active infection with hep B or C or HIV
  • Hypersensitivity or anaphylactic reaction to ganetespib or other HSP90 inhibitors, irinotecan, SN-38 or its derivatives
  • Patients in Phase 1 must not have a genotype of UGT1A1 1*28/*28

Information from the National Library of Medicine

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


Contacts
Contact: Tarveda Clinical Information Center (617) 923-4100 clinical.information@tarvedatx.com

Locations
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
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Tarveda Therapeutics
Investigators
Study Chair: Anish Thomas, MD National Cancer Institute (NCI)

Responsible Party: Tarveda Therapeutics
ClinicalTrials.gov Identifier: NCT03221400     History of Changes
Other Study ID Numbers: PEN-866-001
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Small Cell Lung Carcinoma
Triple Negative Breast Neoplasms
Rhabdomyosarcoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases