Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007200

Trial Description

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Title

A Randomized Phase 2, Double-blind, Placebo-controlled, Multi-center Study Comparing Pemetrexed in Combination With TH-302 vs. Pemetrexed in Combination With Placebo as Second-line Chemotherapy for Advanced Non-Squamous, Non-Small Cell Lung Cancer

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

The purpose of this study is to determine whether TH-302 in combination with pemetrexed is
safe and effective in the treatment of non-squamous non-small cell lung cancer.

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Brief Summary in Scientific Language

TH-302 is designed to target the hypoxic regions of tumors which are generally located
distant from tumor vessels. Pemetrexed has poor tissue penetration and targets the regions
of tumors that are located in proximity to the tumor vessels. The presence of hypoxia in
solid tumors is associated with a more malignant phenotype and resistance to chemotherapy.
The hypoxia-activated prodrug, TH-302, is designed to selectively target the hypoxic
microenvironment. There is evidence supporting the presence of hypoxia in NSCLC lesions
based on a hypoxia PET study. Combining pemetrexed with TH-302 may enable the targeting of
both the normoxic and hypoxic regions of NSCLC lesions.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00007200
  •   2015/07/22
  •   2014/03/18
  •   no
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Secondary IDs

  •   NCT02093962  (ClinicalTrials.gov)
  •   TH-CR-415  (Threshold Pharmaceuticals)
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Health Condition or Problem studied

  •   Non-small Cell Lung Cancer
  •   C34 -  Malignant neoplasm of bronchus and lung
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Interventions/Observational Groups

  •   Drug: TH-302 combination with pemetrexed
  •   Drug: Matched placebo in combination with pemetrexed
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, caregiver, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- Overall survival; time frame: 2 years; To assess the efficacy of pemetrexed in combination with TH-302 as determined by overall survival in patients with advanced non-squamous NSCLC in the second-line chemotherapy setting compared with pemetrexed in combination with placebo

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Secondary Outcome

- Incidence and severity of adverse events in patients treated with TH-302 in combination with pemetrexed vs pemetrexed alone; time frame: 2 years; To assess the safety of TH-302 in combination with pemetrexed compared with placebo and pemetrexed in this setting.
- Population PK of TH-302 in patients treated with TH-302 for measures including clearance and volume of distribution; time frame: 2 years; To investigate the pharmacokinetics of TH-302 in this patient population
- Evaluate anti-tumor activity as measured by progression-free survival and response rate in patients treated with TH-302 in combination with pemetrexed vs pemetrexed alone; time frame: 2 years; To evaluate the anti-tumor activity of pemetrexed in combination with TH-302 compared with pemetrexed in combination with placebo

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Countries of Recruitment

  •   United States
  •   Czech Republic
  •   Germany
  •   Hungary
  •   Italy
  •   Poland
  •   Romania
  •   Russian Federation
  •   Spain
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Locations of Recruitment

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Recruitment

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  •   2014/03/31
  •   440
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Men and women ≥ 18 years of age.

- Histologically or cytologically confirmed stage IIIB or IV NSCLC with non-squamous
histology

- Recurrent or progressive disease after one prior platinum-based non-pemetrexed
chemotherapy treatment for advanced disease with or without maintenance

- Neoadjuvant/adjuvant cytotoxic chemotherapy initiated < 12 months prior to study
randomization will be counted as one prior treatment

- Neoadjuvant/adjuvant cytotoxic chemotherapy initiated ≥ 12 months prior to study
randomization will not be counted as one prior chemotherapy treatment

- Use of targeted agents (e.g., monoclonal antibodies or kinase inhibitors) will not be
counted as a prior chemotherapy treatment

- Patients with known EGFR-activating mutations or ALK rearrangements should have
received treatment with a targeted kinase inhibitor (e.g., erlotinib, crizotinib) and
no longer be considered as a candidate for such treatment

- Measurable disease according to RECIST 1.1

- ECOG performance status 0-1

- Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects
of prior therapy

- Adequate hematologic, hepatic, cardiac, and renal function

- Female patients of childbearing potential must have a negative serum or urine
pregnancy test, whichever is considered standard by the institution

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Exclusion Criteria

- Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or
NSCLC NOS

- Prior therapy with pemetrexed

- Inability or unwillingness to take folic acid, vitamin B12 supplementation or
corticosteroids

- Inability to discontinue non-steroidal anti-inflammatory drugs for 5 days (long
half-life) or for 2 days (short half-life, if CrCL <80 mL/min) before pemetrexed
dosing and until 2 days after pemetrexed dosing

- Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the
following criteria are met:

- brain metastases are stable and have been previously treated with either
whole-brain radiotherapy or gamma-knife surgery

- steroids are currently not required and more than 14 days since last steroid
treatment

- Symptomatic pleural effusion (> CTCAE Grade 1 dyspnea) that is not amenable to
drainage

- Treatment with other systemic anticancer therapy within 4 weeks prior to the first
dose of study medication

- Treatment with full field radiation therapy within 4 weeks or limited field radiation
therapy within 2 weeks prior to the first dose of study medication

- Major surgery within 4 weeks or minor surgery within 2 weeks prior the first dose of
study medication

- Elective or a planned major surgery while on study treatment

- Radiation therapy to greater than 25% of the bone marrow

- Clinically significant active infection (e.g. tuberculosis, viral hepatitis, HIV)

- Any other serious uncontrolled medical disorders or psychological conditions that may
interfere with study conduct

- Concurrent active malignancy other than adequately treated basal cell or squamous
cell carcinoma of the skin or pre-invasive carcinoma of the cervix.

- Pregnant or breast feeding

- Patients who are taking medications that prolong QT interval and have a risk of
Torsades de Pointes (Appendix F) or who have a history of long QT syndrome

- Patients who are taking medications that are strong inducers or inhibitors of CYP3A4

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Addresses

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    • Threshold Pharmaceuticals
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    • EMD Serono
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    • Threshold Pharmaceuticals
    • Tillman Pearce, MD 
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    • Kristin Williams 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2014/11/05
* This entry means the parameter is not applicable or has not been set.