Trial record 1 of 1 for:    NCT01577654
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Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer (TARGET)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Endocyte
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01577654
First received: April 11, 2012
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

This study will test the activity of single-agent EC145 and the combination of EC145 plus docetaxel against the current standard docetaxel in second line Non Small Cell Lung Cancer (NSCLC) (adenocarcinoma, squamous, adenosquamous or adenocarcinoma with other NSCLC variants of the lung) in participants with all target lesions expressing the folate receptor [FR(++)].


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: EC145
Drug: EC145 + Docetaxel
Drug: Docetaxel
Drug: EC20
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Phase 2 Study of EC145 Single-agent and the Combination of EC145 Plus Docetaxel Versus Docetaxel Alone in Participants With Folate-receptor Positive [FR(++)] Second Line NSCLC

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression free survival(PFS)based on investigator assessment using RECIST v1.1 [ Time Frame: From date of baseline disease assessment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 26 months ] [ Designated as safety issue: No ]
    Disease assessment will be conducted via CT/ MRI every 6 weeks while on study. Participants who come off study due to any other reason except progression of disease or death will be followed via CT/ MRI every 6 weeks until disease progression or until start of new therapy.


Secondary Outcome Measures:
  • Compare overall response rate of participants between treatment arms. [ Time Frame: up to 26 months ] [ Designated as safety issue: No ]
    Analysis will occur when approximately 50% of the PFS events have occurred (for each comparison) and when 94 PFS events have occurred.

  • Compare disease control rate of participants between treatment arms. [ Time Frame: up to 26 months ] [ Designated as safety issue: No ]
    Analysis will occur when approximately 50% of the PFS events have occurred (for each comparison) and when 94 PFS events have occurred.

  • Compare duration of response of participants between treatment arms. [ Time Frame: up to 26 months ] [ Designated as safety issue: No ]
    Analysis will occur when approximately 50% of the PFS events gave occurred (for each comparison) and when 94 PFS events have occurred.

  • Compare duration of disease control of participants between treatment arms. [ Time Frame: up to 26 months ] [ Designated as safety issue: No ]
    Analysis will occur when approximately 50% of the PFS events gave occurred (for each comparison) and when 94 PFS events have occurred.

  • Compare overall survival of participants between treatment arms. [ Time Frame: up to 26 months ] [ Designated as safety issue: No ]
    Analysis will occur when approximately 50% of the PFS events gave occurred (for each comparison) and when 94 PFS events have occurred.

  • Incidence of Adverse Events, Serious Adverse Events, and Deaths. [ Time Frame: up to 26 months ] [ Designated as safety issue: Yes ]
    Adverse events (as a measure of safety and tolerability) will be assessed at each study visit.


Enrollment: 203
Study Start Date: March 2011
Estimated Study Completion Date: January 2015
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: EC145 alone
EC145 alone
Drug: EC145
2.5 mg on Days 1,4,8,11 (Weeks 1 and 2 q3 weeks)
Other Name: Vintafolide
Drug: EC20
During the screening period participants will receive a single intravenous administration of EC20 prior to SPECT imaging
Other Name: Etarfolatide
Experimental: Arm B: EC145 + Docetaxel
EC145 + Docetaxel
Drug: EC145 + Docetaxel

EC145 2.5 mg on Days 1,4,8,11 (Weeks 1 and 2 q3 weeks) +

Docetaxel 75 mg/m2 IV Day 1 q 3 weeks

Other Names:
  • Vintafolide
  • Taxotere
Drug: EC20
During the screening period participants will receive a single intravenous administration of EC20 prior to SPECT imaging
Other Name: Etarfolatide
Active Comparator: Arm C: Docetaxel alone
Docetaxel alone
Drug: Docetaxel
75 mg/m2 IV Day 1 q 3 weeks
Other Name: Taxotere
Drug: EC20
During the screening period participants will receive a single intravenous administration of EC20 prior to SPECT imaging
Other Name: Etarfolatide

Detailed Description:

In a phase 2 study of single-agent EC145 in heavily pretreated non-small cell lung cancer (NSCLC) patients (median of 3 prior chemotherapy regimens), the subgroup with all target lesions expressing the folate receptor [FR(++)] had a promising prolonged progression free survival of 7.1 months and overall survival of 10.9 months. Furthermore, in-vitro and in-vivo studies in KB models showed good synergism between EC145 and docetaxel.

This study will clinically assess for the first time the combination of EC145+docetaxel (Arm B) in participants with NSCLC (Stage IIIB or IV). This is an international, multicenter, centrally randomized, open-label, phase 2 study comparing single-agent EC145, EC145+docetaxel combination therapy, and single-agent docetaxel in participants with NSCLC who have failed one prior chemotherapy and who have all target lesions expressing the folate receptor [FR(++)]. Eligible participants will be randomized in a 1:1:1 ratio into either Arm A (single-agent EC145), Arm B (EC145+docetaxel combination therapy), or Arm C (single-agent docetaxel) and will receive treatment until either disease progression or intolerable toxicity.

This study is intended to investigate if there is a sufficiently strong efficacy signal in order to proceed with phase 3 testing with either EC145 single-agent and/or the combination of EC145+docetaxel against the standard-of-care docetaxel in second-line NSCLC.

This study will clinically assess for the first time the combination of EC145+docetaxel (Arm B) in participants with NSCLC (Stage IIIB or IV). Therefore, an interim safety analysis will be done by the DSMB after 5 participants in Arm B have completed 1 cycle of therapy, and the second analysis after 15 participants in Arm B have completed 1 cycle of therapy.

If the majority of the enrolled participants (more than 70%) require a dose reduction of one level (to 60 mg/m2), the dose will be reduced for the remainder of the study. If the majority of the participants (more than 70%) require 2 dose reductions (to 40 mg/m2), the sponsor will consider discontinuing the combination arm.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to sign an approved informed consent form (ICF).
  2. Must be ≥ 18 years of age.
  3. Histology confirmed diagnosis of non-small cell lung cancer (adenocarcinoma, squamous, adenosquamous, or adenocarcinoma with other NSCLC variants of the lung) (Stage IIIB or IV).
  4. All (RECIST v1.1-defined) target lesions positive for the folate receptor [FR(++)] by SPECT scan.
  5. Only one prior systemic therapy for advanced disease (e.g.,a platinum doublet or a maintenance regimen that includes a platinum doublet; in addition, the participant may have received an epidermal growth factor receptor [EGFR] inhibitor).
  6. Radiological evaluation conducted no more than 28 days prior to beginning study therapy. If history of CNS metastasis baseline radiological imaging must include brain MRI or CT.
  7. Radiologic evidence of disease progression following the most recent prior treatment.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  9. Must have recovered (to baseline/stabilization) from prior cytotoxic-therapy-associated acute toxicities.
  10. Prior radiation therapy is allowed if the following criteria is met:

    • Radiation to < 25% of the bone marrow; whole pelvis radiation is excluded.
    • Prior radiotherapy must be completed at least 2 weeks before randomization.
    • Must have recovered from the acute toxic effects of the treatment before randomized.
    • Prior thoracic radiation must be completed 30 days before study enrollment.
    • Irradiated pulmonary lesions cannot be used as target or non-target lesions (and must be excluded) unless there is previous documented progression of these lesions.
    • Palliative extrathoracic radiotherapy can continue, but these lesions must be excluded as target and non-target lesions.
  11. Adequate organ function:

    • Bone marrow reserve: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelets ≥ 100 x 109/L. Hemoglobin ≥ 9 g/dL.
    • Hepatic: Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH) and alkaline phosphatase ≤ 2.5 x ULN.
    • Renal: Serum creatinine ≤ 1.5 x ULN, or for participants with serum creatinine > 1.5 ULN, creatinine clearance ≥ 50 mL/min/1.73 m2 (50mL/min/1.73m2 is equivalent to 0.83 mL/s/m2).
  12. Participants of childbearing potential:

    • Women who are capable of becoming pregnant must have a negative serum pregnancy test within 1 week prior to exposure to EC20 and within 1 week prior to exposure to treatment with EC145 and/or docetaxel.
    • Women who are capable of becoming pregnant and male participants who are sexually active must practice an effective method of birth control for the duration of their participation in the trial through 3 months following the last dose of EC145 and through 6 months following the last dose of docetaxel.

Exclusion Criteria:

  1. Prior therapy with docetaxel, vinorelbine, or vinca-containing compounds.
  2. Known hypersensitivity to docetaxel or polysorbate 80.
  3. Symptomatic central nervous system (CNS) metastases or metastases that result in midline shift, significant edema.
  4. Malignancies other than NSCLC that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or low-grade (Gleason score ≤ 6) localized prostate cancer and patients with prior history of malignancy who have been disease free for more than 3 years are eligible.
  5. Serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension.
  6. Anti-folate therapy such as methotrexate for rheumatoid arthritis.
  7. Baseline peripheral neuropathy CTCAE ≥ Grade 2.
  8. Pregnant or lactating women.
  9. Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.
  10. Active infections (e.g., hepatitis or HIV carriers)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01577654

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Endocyte
Investigators
Study Director: Binh Nguyen, MD, PhD Endocyte
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01577654     History of Changes
Other Study ID Numbers: 8109-003, 2012-000966-40
Study First Received: April 11, 2012
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
adenocarcinoma
squamous
adenosquamous
adenocarcinoma with other NSCLC variants
EC145
EC20
Vintafolide
Etarfolatide

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014