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:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Anal Squamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Endometrial Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
  • Pancreatic Adenocarcinoma
  • Small Cell Lung Carcinoma
  • Squamous Cell Carcinoma of the Penis
  • Vulvar Squamous Cell 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
  • 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
  • Squamous Cell Carcinoma of the Vulva
  • Squamous Cell Carcinoma of the Penis
  • Gastric Cancer
  • Gastric Adenocarcinoma
  • Gastroesophageal Junction Adenocarcinoma
  • Small-cell Lung Cancer
  • Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
PEN-866 SodiumPEN-866 Sodium

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-866 SodiumExperimentalIntravenous administration of PEN-866 Sodium
  • PEN-866 Sodium

Eligibility 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:

               -  Small Cell Lung Cancer (SCLC): Patients with locally recurrent or metastatic SCLC
                  whose disease has progressed after having received one or more prior lines of
                  chemotherapy.

               -  Gastric or gastroesophageal (GEJ) adenocarcinoma: Patients with locally recurrent
                  or metastatic gastric or GEJ adenocarcinoma whose disease has progressed after
                  having received one or more prior lines of chemotherapy.

               -  Squamous cell carcinoma (SCC) of the genitalia (anus, cervix, vulva, or penis):
                  Patients with locally recurrent or metastatic SCC of the genitalia (anus, cervix,
                  vulva, or penis) whose disease has progressed after having received one or more
                  prior lines of chemotherapy, including those whose disease has progressed after
                  postoperative adjuvant chemotherapy or neoadjuvant chemotherapy prior to
                  radiation or surgery.

               -  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.

        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. Prior treatment with topoisomerase I inhibitor(s).

          3. 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

          4. Stroke or transient ischemic attack within 6 months of screening

          5. Peripheral neuropathy greater than grade 2

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

          7. History of leptomeningeal disease or spinal cord compression

          8. Brain metastases unless asymptomatic and not requiring steroids for at least 4 weeks
             prior to start of study treatment

          9. As judge by the Investigator major surgery within 28 days of first drug dose

         10. Female pregnant or breast feeding

         11. Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver
             transplant, active infection with hep B or C or HIV

         12. Hypersensitivity or anaphylactic reaction to ganetespib or other HSP90 inhibitors,
             irinotecan, SN-38 or its derivatives
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Maximum concentration (Cmax) of PEN-866 and its components (HSP90 ligand and SN-38)
Time Frame:1 Month
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866 and its components (HSP90 targeting ligand and SN-38)
Measure:Area under the curve (AUC) of PEN-866 and its components (HSP90 ligand and SN-38)
Time Frame:1 Month
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866 and its components (HSP90 targeting ligand and SN-38)
Measure:Half-life (t1/2) of PEN-866 and its components (HSP90 ligand and SN-38)
Time Frame:1 Month
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866 and its components (HSP90 targeting ligand and SN-38)
Measure: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)
Safety Issue:
Description:Size of tumors by CT or MRI using tumor response criteria according to RECIST 1.1 and duration of response.
Measure:Phase 2a: Disease Control Rate in patients with SCLC, gastric or gastroesophageal junction adenocarcinoma, endometrial adenocarcinoma, and squamous cell carcinoma of the genitalia (anus, cervix, vulva, and penis)
Time Frame:From date of first treatment through the date of date of first documented progression, assessed up to (estimated) 18 months
Safety Issue:
Description:Efficacy of PEN-866 in SCLC, gastric or gastroesophageal junction adenocarcinoma, endometrial adenocarcinoma, and squamous cell carcinoma of the genitalia (anus, cervix, vulva, and penis) will be assessed using DCR as defined as CR, PR, or SD according to RECIST 1.1.
Measure:Phase 2a: Evaluate the best overall response rate in patients with pancreatic adenocarcinoma
Time Frame:From date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months
Safety Issue:
Description:Efficacy of PEN-866 in pancreatic adenocarcinoma using best overall tumor response rate as defined as CR or PR according to RECIST 1.1
Measure:Phase 2a: Duration of Response
Time Frame:From date of first treatment until the date of date of death from any cause, assessed up to (estimated) 18 months
Safety Issue:
Description:Time from first documented response (CR or PR) to date of first documented disease progression or death due to underlying cancer.
Measure:Phase 2a: Radiographic progression free survival
Time Frame:From date of first treatment until the date of first documented progression or date of death from any cause, whichever is first, assessed up to (estimated) 18 months
Safety Issue:
Description:Time from first PEN-866 dose to date of first documented progression or date of death from any cause, whichever came first
Measure:Phase 2a: Overall survival
Time Frame:From date of first treatment until the date of date of death from any cause, assessed up to (estimated) 18 months
Safety Issue:
Description:Time from first PEN-866 dose to date of death from any cause

Details

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

Last Updated

February 26, 2020