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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 : August 29, 2019
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 Endometrial Adenocarcinoma Neoplasms Squamous Cell Carcinoma of the Anus Adenocarcinoma of the Pancreas Advanced Cancer Solid Tumor Solid Carcinoma Squamous Cell Carcinoma of the Cervix Squamous Cell Carcinoma of the Head and Neck Drug: PEN-866 Sodium 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.


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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 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PEN-866 Sodium
Intravenous administration of PEN-866 Sodium
Drug: PEN-866 Sodium
PEN-866 Sodium 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. Phase 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) and Recommended Phase 2 Dose (RP2D) will be determined by assessing the incidence of DLTs and treatment related adverse events.

  2. Incidence of treatment related adverse events (Safety and tolerability) [ Time Frame: From date of first treatment/trial entry up to 28 days following the last treatment. ]
    Safety and tolerability will be determined by assessing the incidence of treatment related adverse events.

  3. Phase 2a: Efficacy of PEN-866 in pancreatic adenocarcinoma using Disease Control Rate (DCR) [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months ]
    Efficacy of PEN-866 in pancreatic adenocarcinoma will be assessed using DCR as defined as a best response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.

  4. Phase 2a: Efficacy of PEN-866 in endometrial adenocarcinoma and squamous cell carcinoma of the anus, cervix, or head and neck using best overall response rate [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months ]
    Efficacy of PEN-866 in endometrial adenocarcinoma and squamous cell carcinoma of the anus, cervix, or head and neck will be assessed using best overall tumor response rate as defined as complete response (CR) or partial response (PR) according to RECIST 1.1.


Secondary Outcome Measures :
  1. Maximum concentration (Cmax) of PEN-866 and its components (HSP90 targeting ligand and SN-38) [ Time Frame: 1 Month ]
    Characterize the pharmacokinetic properties of PEN-866 and its components (HSP90 ligand and SN-38)

  2. Area under the curve (AUC) of PEN-866 and its components (HSP90 ligand and SN-38) [ Time Frame: 1 Month ]
    Characterize the pharmacokinetic properties of PEN-866

  3. Half-life (t1/2) of PEN-866 and its components (HSP90 ligand and SN-38) [ Time Frame: 1 Month ]
    Characterize the pharmacokinetic properties of PEN-866

  4. Phase 1: Tumor response using RECIST 1.1 criteria [ Time Frame: Baseline and every 6 weeks until date of first documented progression or death (estimated 6 months) ]
    Size of tumors by CT or MRI according to RECIST 1.1 criteria

  5. Phase 2a: Efficacy of PEN-866 in pancreatic adenocarcinoma using best overall tumor response rate [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months ]
    Efficacy of PEN-866 in pancreatic adenocarcinoma using best overall tumor response rate as defined as CR or PR according to RECIST 1.1.

  6. Phase 2a: Efficacy of PEN-866 in endometrial adenocarcinoma and squamous cell carcinoma of the anus, cervix, or head and neck using Disease Control Rate (DCR) [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months ]
    Efficacy of PEN-866 in endometrial adenocarcinoma and squamous cell carcinoma of the anus, cervix, or head and neck will be assessed using DCR as defined as complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.

  7. Phase 2a: Duration of Response [ Time Frame: From date of first treatment/trial entry until the date of date of death from any cause, assessed up to (estimated) 18 months ]
    Time from first documented response (CR or PR) to date of first documented disease progression or death due to underlying cancer.

  8. Phase 2a: 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 (estimated) 18 months ]
    Time from first PEN-866 dose to date of first documented progression or date of death from any cause, whichever came first

  9. Phase 2a: Overall survival [ Time Frame: From date of first treatment/trial entry until the date of date of death from any cause, assessed up to (estimated) 18 months ]
    Time from first PEN-866 dose to date of death from any cause



Information from the National Library of Medicine

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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:

  1. M/F at least 18 years old
  2. Performance status 0 or 1
  3. Adequate bone marrow, liver, and kidney function within 28 days prior to first dose
  4. Serum potassium, calcium, magnesium, phosphorus within normal limits
  5. Adequate birth control
  6. Central venous access line is required
  7. 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
  8. 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.
  9. Patients in Phase 2a must have disease history specific to their disease as listed below:

    • Pancreatic adenocarcinoma (PDAC): Patients with locally recurrent or metastatic PDAC whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.
    • Endometrial adenocarcinoma (EC): Patients with locally recurrent or metastatic EC whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy. Patients are ineligible if they have received a topoisomerase inhibitor.
    • Squamous cell carcinoma of the anus, cervix, or head and neck: Patients with locally recurrent or metastatic squamous cell carcinoma of the anus, cervix, or head and neck whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.

Exclusion Criteria:

  1. 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
  2. Cardiac disease such as unstable angina within 6 months of screening, myocardial infarction within 6 months of screening, NY Heart Association Class III - IV 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
  3. Stroke or transient ischemic attack within 6 months of screening
  4. Peripheral neuropathy greater than grade 2
  5. Patients requiring medications with drugs that are inhibitors of UGT1A1 or substrates of CYP1A2, P-gP, BCRP, OATP1B1, OATP1B3 or OCT1 transporters
  6. History of leptomeningeal disease or spinal cord compression
  7. Brain metastases unless asymptomatic and not requiring steroids for at least 4 weeks prior to start of study treatment
  8. As judge by the Investigator major surgery within 28 days of first drug dose
  9. Female pregnant or breast feeding
  10. Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver transplant, active infection with hep B or C or HIV
  11. Hypersensitivity or anaphylactic reaction to ganetespib or other HSP90 inhibitors, irinotecan, SN-38 or its derivatives

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

Locations
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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, Oklahoma
Stephenson Cancer Center, University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Tarveda Therapeutics
Investigators
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Study Chair: Anish Thomas, MD National Cancer Institute (NCI)

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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: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Squamous Cell Carcinoma of Head and Neck
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases