Clinical Trials /

PEN-866 in Patients With Advanced Solid Malignancies

NCT03221400

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Ewing Sarcoma
  • Gastric Adenocarcinoma
  • Pancreatic Adenocarcinoma
  • Rhabdomyosarcoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PEN-866 in Patients With Advanced Solid Malignancies
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PEN-866-001
  • NCT ID: NCT03221400

Conditions

  • 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

Interventions

DrugSynonymsArms
PEN-866PEN-866

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
PEN-866ExperimentalIntravenous administration of PEN-866
  • PEN-866

Eligibility Criteria

        Inclusion Criteria:

          -  M/F at least 18 years old

          -  Performance status 0 or 1

          -  Adequate bone marrow, liver, and kidney function within 2 weeks prior to first dose

          -  Serum potassium, calcium, magnesium, phosphorus within normal limits

          -  Adequate birth control

          -  Patients in Phase 1 must also have confirmed advanced solid malignancy that has
             progressed after one or more prior lines of anticancer therapy

          -  Patients in Phase 2 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

        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

          -  Any other malignancy known to be active

          -  Cardiac disease such as unstable angina, myocardial infarction within 6 months of
             screening

          -  Stroke or transient ischemic attack within 6 months of screening

          -  Peripheral neuropathy greater than grade 1

          -  Patients requiring medications with drugs that are inhibitors of UGT1A1 or substrates
             of CYP1A2, P-gP, BCRP, OATP1B1, OATP1B3 or OCT1

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame:Patients will be followed for 28 days in Cycle 1 to determine the incidence of DLTs.
Safety Issue:
Description:In Phase 1, the Maximum Tolerated Dose (MTD) will be determined by assessing the incidence of DLTs and treatment related adverse events.

Secondary Outcome Measures

Measure:Maximum concentration of PEN-866 and its metabolites (Cmax)
Time Frame:1 Month
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866
Measure:Area under the curve (AUC) of PEN-866 and its metabolites
Time Frame:1 Month
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866
Measure:Half-life (t1/2) of PEN-866 and its metabolites
Time Frame:1 Month
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866
Measure:Tumor response using RECIST criteria
Time Frame:2 Months
Safety Issue:
Description:In Phase 1, size of tumors by CT or MRI (RECIST)
Measure: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
Safety Issue:
Description:In Phase 2, size of tumors by CT or MRI (RECIST)
Measure: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
Safety Issue:
Description:In Phase 2, time to death

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tarveda Therapeutics

Last Updated

July 31, 2017