Clinical Trials /

PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers

NCT02936323

Description:

Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung.

Related Conditions:
  • Colon Neuroendocrine Neoplasm
  • Gastric Neuroendocrine Tumor
  • Large Cell Lung Neuroendocrine Carcinoma
  • Lung Neuroendocrine Neoplasm
  • Merkel Cell Carcinoma
  • Neuroendocrine Carcinoma
  • Neuroendocrine Tumor
  • Pancreatic Neuroendocrine Tumor
  • Paraganglioma
  • Pheochromocytoma
  • Small Cell Lung Carcinoma
  • Small Intestinal Neuroendocrine Tumor
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers
  • Official Title: A Phase 1/2a, Open-label Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of PEN-221 in Patients With Somatostatin Receptor 2 Expressing Advanced Cancers, Including Gastroenteropancreatic or Lung or Thymus or Other Neuroendocrine Tumors or Small Cell Lung Cancer or Large Cell Neuroendocrine Carcinoma of the Lung

Clinical Trial IDs

  • ORG STUDY ID: PEN-221-001
  • NCT ID: NCT02936323

Conditions

  • Neuroendocrine Tumors
  • Carcinoma, Small Cell Lung
  • Neuroendocrine Carcinoma

Interventions

DrugSynonymsArms
PEN-221PEN-221

Purpose

Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung.

Detailed Description

      Protocol PEN-221-001 will first enroll patients into a dose escalation phase, where a
      Bayesian logistic regression model, guided by the escalation with overdose control principle
      and overseen by a safety review committee, will be used to make dose recommendations and
      estimate the maximum tolerated dose (MTD).

      Once the MTD has been confirmed, remaining patients will be enrolled into a full expansion
      phase to assess PEN-221 efficacy in patients with gastrointestinal mid-gut neuroendocrine
      tumors or pancreatic neuroendocrine tumors or small cell lung cancer.
    

Trial Arms

NameTypeDescriptionInterventions
PEN-221Experimentalintravenous administration of PEN-221
  • PEN-221

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 (may be
             supplemented)

          -  Adequate birth control

          -  Somatostatin receptor 2 positive tumor as assessed at pre-screening or within 180 d of
             first drug dose using indium SPECT or gallium PET

        Patients in Phase 1 must have a histologically or cytologically-confirmed solid tumor in 1
        of the following categories:

          -  Advanced small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC)
             of lung progressed after at least 1 line of anticancer chemotherapy

          -  Advanced low or intermediate grade gastroenteropancreatic or lung or thymus
             neuroendocrine tumor (NET), or NET of unknown primary, progressed after at least 1
             line of anticancer therapy (unless no standard treatments available or such treatments
             are deemed not appropriate)

          -  Advanced paraganglioma, pheochromocytoma, medullary thyroid carcinoma, Merkel cell
             carcinoma, or high grade extrapulmonary neuroendocrine carcinoma having progressed
             after 1 or more lines of anticancer chemotherapy (unless no standard treatments
             available or such treatments are deemed not appropriate)

        For patients enrolling once escalation is complete (Phase 2a), disease must be measurable
        per RECIST 1.1 criteria with last imaging performed within 28 days prior to first drug dose

        In addition to the criterion listed above, Patients in Phase 2a must have a histologically-
        or cytologically-confirmed, advanced or metastatic solid tumor, in 1 of the following
        categories: disease history specified in one of the criteria listed below:

          -  Well differentiated, low or intermediate grade, gastrointestinal mid-gut (arising from
             the lower jejunum, ileum, appendix, cecum, and proximal colon) NET with documented
             disease progression within 6 months prior to start of study treatment and evidence of
             radiographic disease progression based on scans performed not more than 15 months
             apart. Patients may have received 1 or more prior lines of anticancer therapy, such as
             somatostatin analogues, targeted agents, or liver-directed intra-arterial therapy, but
             are NOT eligible if they have received prior systemic cytotoxic chemotherapy or
             peptide receptor radionuclide therapy (PRRT).

          -  Well differentiated, low or intermediate grade, pancreatic NET with documented disease
             progression within 6 months prior to start of study treatment and evidence of
             radiographic disease progression based on scans performed not more than 15 months
             apart. Patients may have received 1 or more prior lines of anticancer therapy, such as
             somatostatin analogues, targeted agents, or liver-directed intra-arterial therapy, and
             up to 1 prior line of systemic cytotoxic chemotherapy, but are NOT eligible if they
             have received more than 1 prior line of systemic cytotoxic chemotherapy or if they
             have received prior peptide receptor radionuclide therapy (PRRT)

          -  SCLC after having received up to three prior lines of anticancer therapy.

        Exclusion Criteria:

          -  Treatment with anticancer therapy or investigational drug or device within 3 wk (6 wk
             for nitrosureas or mitomycin C) or 5 half-lives of agent, whichever is shorter, prior
             to first PEN-221 drug dose, and any drug-related toxicities must have recovered to
             grade 1 or less

          -  Any other malignancy known to be active or treated within 3 years of start of
             screening, except cervical intra-epithelial neoplasia and non-melanoma skin cancer

          -  Cardiac criteria 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 1

          -  Requirement for medication with strong CYP3A4 inhibitor

          -  History of leptomeningeal disease or spinal cord compression

          -  Brain metastases unless asymptomatic on a stable low dose of steroids. Patients with
             SCLC or LCNEC of lung only must have CT or MRI of brain during screening, and if
             metastases found, must have radiotherapy with 14 day washout or stereotactic
             radiotherapy or radio surgery with 7 day washout prior to first drug dose.

          -  Major surgery within 28 days of first drug dose

          -  Female who is pregnant or breast feeding

          -  Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver
             transplant, active infection with hepatitis B or C, or HIV

          -  Hypersensitivity or anaphylactic reaction to any somatostatin analog or to
             maytansinoids
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:High Grade (>=Grade 3) Treatment related adverse events
Time Frame:From date of first treatment/trial entry until 28 days after last treatment, estimated 12 months
Safety Issue:
Description:Treatment related adverse events are assessed using CTCAE criteria.

Secondary Outcome Measures

Measure:Maximum concentration of PEN-221 and its metabolites (Cmax)
Time Frame:up to 2 months
Safety Issue:
Description:Maximum concentration of PEN-221 concentration in circulating blood
Measure:Area under the curve (AUC) of PEN-221 and its metabolites
Time Frame:up to 2 months
Safety Issue:
Description:Area under PEN-221 concentration v time curve in circulating blood
Measure:Half-life (t1/2) of PEN-221 and its metabolites
Time Frame:up to 2 months
Safety Issue:
Description:Half life of PEN-221 concentration in circulating blood
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 came first, assessed up to (estimated) 36 months
Safety Issue:
Description:Radiographic progression free survival based on assessment of tumor size by CT or MRI (RECIST 1.1)
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 (estimated) 36 months
Safety Issue:
Description:Time to death

Details

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

Trial Keywords

  • SCLC small cell lung cancer
  • pancreatic neuroendocrine NET
  • GI neuroendocrine NET

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