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 SodiumPhase 1a PEN-866 Sodium (Single Agent)
fluorouracil5-Fluorouracil, 5-FUPhase 1b PEN-866 Sodium + Flurouracil + Folinic Acid
Folinic acidLeucovorinPhase 1b PEN-866 Sodium + Flurouracil + Folinic Acid

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 1a will employ an adaptive model guided with overdose control principle to make dose
      recommendations and estimate the maximum tolerated dose (MTD) of PEN-866 (single agent).

      Phase 1b will employ a standard 3 + 3 design to make dose recommendations and estimate the
      MTD of combination therapy in patients with pancreatic adenocarcinoma (PDAC).

      Phase 2a (single agent) begins once all patients treated in Phase 1a 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 1a (single agent) based on the safety,
      tolerability, pharmacokinetic, and pharmacodynamics profile of PEN-866 (single agent)during
      Phase 1a.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1a PEN-866 Sodium (Single Agent)ExperimentalDose escalation of PEN-866 Sodium administered intravenously
  • PEN-866 Sodium
Phase 1b PEN-866 Sodium + Flurouracil + Folinic AcidExperimentalDose escalation of intravenous administration of PEN-866 Sodium in combination with fluorouracil and folinic acid
  • PEN-866 Sodium
  • fluorouracil
  • Folinic acid
Phase 2a PEN-866 Sodium (Single Agent)ExperimentalIntravenously administered PEN-866 Sodium at the Recommended Phase 2 Dose
  • 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 1a and Phase 1b 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.

         10. For Phase 1b patients only: Patients with metastatic PDAC who have 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) before C1D1, and any drug-related toxicities must have
             recovered to grade 1 or less with the exception of alopecia and peripheral neuropathy.

          2. Phase 2a only: 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. Stable low dose of steroids is permitted.

          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

         13. Any medical, psychological, or social condition that would interfere with the
             patient's participation in the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1a and 1b : Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame:Patients will be followed for 28 days to determine the incidence of DLTs.
Safety Issue:
Description: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 of PEN-866 as a single agent (Phase 1a) or in combination therapy (Phase 1b).

Secondary Outcome Measures

Measure:Maximum concentration (Cmax) of PEN-866 and its components (HSP90 ligand and SN-38)
Time Frame:1 Month (Phase 1a); 14 days (Phase 1b); assessed up to (estimated) 18 months for Phase 2a
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 (Phase 1a); 14 days (Phase 1b); assessed up to (estimated) 18 months for Phase 2a
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 (Phase 1a); 14 days (Phase 1b); assessed up to (estimated) 18 months for Phase 2a
Safety Issue:
Description:Characterize the pharmacokinetic properties of PEN-866 and its components (HSP90 targeting ligand and SN-38)
Measure:Phase 1b: Characterize the plasma pharmacokinetics (PK) of the combination therapies and their components
Time Frame:14 days
Safety Issue:
Description:PK parameters (CMax, AUC) will be evaluated in plasma by standard non-compartmental methods (compartmental modeling may be performed if appropriate).
Measure:Phase 1a: 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 1b: Disease Control Rate
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 combination therapy will be assessed using DCR as defined as CR, PR, or SD according to RECIST 1.1.
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 1b and 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

August 14, 2020