Clinical Trials /

Carboplatin and Paclitaxel With or Without Ramucirumab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Thymic Cancer That Cannot Be Removed by Surgery

NCT03694002

Description:

This randomized phase II trial studies how well carboplatin and paclitaxel with or without ramucirumab work in treating patients with thymic cancer that has spread to other places in the body, has come back, or cannot be removed by surgery. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ramucirumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if giving carboplatin and paclitaxel with or without ramucirumab will work better in treating patients with thymic cancer.

Related Conditions:
  • Thymic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Carboplatin and Paclitaxel With or Without Ramucirumab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Thymic Cancer That Cannot Be Removed by Surgery
  • Official Title: A Randomized Phase II Trial of Carboplatin-Paclitaxel With or Without Ramucirumab in Patients With Unresectable Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: S1701
  • SECONDARY ID: NCI-2017-02254
  • SECONDARY ID: S1701
  • SECONDARY ID: S1701
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT03694002

Conditions

  • Locally Advanced Thymic Carcinoma
  • Metastatic Thymic Carcinoma
  • Recurrent Thymic Carcinoma
  • Unresectable Thymic Carcinoma

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboArm A (ramucirumab, carboplatin, paclitaxel)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm A (ramucirumab, carboplatin, paclitaxel)
Ramucirumabanti-VEGFR-2 fully human monoclonal antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2Arm A (ramucirumab, carboplatin, paclitaxel)

Purpose

This randomized phase II trial studies how well carboplatin and paclitaxel with or without ramucirumab work in treating patients with thymic cancer that has spread to other places in the body, has come back, or cannot be removed by surgery. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ramucirumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if giving carboplatin and paclitaxel with or without ramucirumab will work better in treating patients with thymic cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare progression-free survival between patients with incurable unresectable locally
      advanced, or recurrent, or metastatic thymic carcinoma randomized to carboplatin-paclitaxel
      with or without ramucirumab.

      SECONDARY OBJECTIVES:

      I. To evaluate the frequency and severity of toxicity of carboplatin-paclitaxel with or
      without ramucirumab in this patient population.

      II. To compare the response rate (complete response, partial response, confirmed and
      unconfirmed) between treatment arms.

      III. To compare disease control rate (complete response, partial response, confirmed or
      unconfirmed, stable disease) between treatment arms.

      IV. To compare overall survival between treatment arms.

      TERTIARY OBJECTIVES:

      I. To bank specimens for future research.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients receive ramucirumab intravenously (IV) over 60 minutes, carboplatin IV, and
      paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of
      disease progression or unacceptable toxicity. Patients who have not progressed may continue
      to receive ramucirumab for up to 1 year.

      ARM B: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 21
      days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 1 year, and
      then every 6 months for 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (ramucirumab, carboplatin, paclitaxel)ExperimentalPatients receive ramucirumab IV over 60 minutes, carboplatin IV, and paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have not progressed may continue to receive ramucirumab for up to 1 year.
  • Carboplatin
  • Paclitaxel
  • Ramucirumab
Arm B (carboplatin, paclitaxel)Active ComparatorPatients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed thymic carcinoma

          -  Patients must have unresectable thymic carcinoma that is either locally advanced,
             recurrent, or metastatic

          -  Patients must not be candidates for localized surgery

          -  Patients must have measurable disease documented by computed tomography (CT) or
             magnetic resonance imaging (MRI) within 28 calendar days prior to randomization; the
             CT from a combined positron emission tomography (PET)/CT may be used only if it is of
             diagnostic quality; non-measurable disease must be assessed within 42 calendar days
             prior to randomization; all known sites of disease must be assessed and documented on
             the baseline tumor assessment form (Response Evaluation Criteria in Solid Tumors
             [RECIST] 1.1)

          -  Patients must have a Zubrod performance status of 0 to 2

          -  Patients must not have undergone major surgery within 28 calendar days prior to
             randomization, or minor surgery/subcutaneous venous access device placement within 7
             calendar days prior to randomization; the patient must not have elective or planned
             major surgery to be performed during the course of the clinical trial

          -  Patients must not have had prior systemic anti-cancer therapy for locally advanced or
             metastatic unresectable thymic carcinoma

          -  If patients have recurrent unresectable thymic carcinoma, patients may have had prior
             neoadjuvant or adjuvant chemotherapy if treatment concluded >= 6 months prior to
             randomization

          -  Patients must have a CT or MRI scan of the brain to evaluate for central nervous
             system (CNS) disease within 42 calendar days prior to registration; patient must not
             have brain metastases unless: (1) metastases have been treated and have remained
             controlled for at least two weeks following treatment, AND (2) patient has no residual
             neurological dysfunction off corticosteroids for at least 1 day

          -  Patients must not be candidates for radiation therapy with curative intent; prior
             palliative radiation therapy is allowed as long as a period of 7 days has passed since
             the last dose was received and the patient has recovered from any associated toxicity
             at the time of randomization

          -  Absolute neutrophil count (ANC) >= 1500/mcL documented within 28 calendar days prior
             to randomization

          -  Hemoglobin >= 9 g/dL (5.58 mmol/L) documented within 28 calendar days prior to
             randomization

          -  Platelets >= 100,000/mcL documented within 28 calendar days prior to randomization

          -  International normalized ratio (INR) =< 1.5 documented within 28 calendar days prior
             to randomization

          -  Partial thromboplastin time (PTT) =< 5 seconds above the institutional upper limit of
             normal (IULN) (unless receiving anticoagulation therapy) documented within 28 calendar
             days prior to randomization

          -  Patients receiving warfarin must be switched to low molecular weight heparin and have
             achieved stable coagulation profile 14 days prior to randomization

          -  Patients must not have experienced any grade 3 or above gastrointestinal (GI) bleeding
             within 84 calendar days prior to randomization

          -  Patients must not have a history of deep vein thrombosis (DVT), pulmonary embolism
             (PE), or any other significant thromboembolism (venous port or catheter thrombosis or
             superficial venous thrombosis are not considered ?significant?) during the 84 calendar
             days prior to randomization

          -  Total bilirubin =< 1.5 x the institutional upper limit normal (IULN) documented within
             28 calendar days prior to randomization

          -  Aspartate aminotransferase (aspartate transaminase [AST]) and alanine aminotransferase
             (alanine transaminase [ALT]) =< 3.0 x IULN; for patients with liver metastases, total
             bilirubin and AST or ALT must be =< 5.0 x IULN documented within 28 calendar days
             prior to randomization

          -  Patients must not have any of following:

               -  Cirrhosis at a level of Child-Pugh B (or worse)

               -  Cirrhosis (any degree) and a history of hepatic encephalopathy; or

               -  Clinically meaningful ascites resulting from cirrhosis; clinically meaningful
                  ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis

          -  Serum creatinine =< 1.5 x IULN, or creatinine clearance (measured via 24-hour urine
             collection) >= 40 mL/minute (that is, if serum creatinine is > 1.5 x ULN, a 24-hour
             urine collection to calculate creatinine clearance must be performed) documented
             within 28 calendar days prior to randomization

          -  Patient urinary protein must be =< 1+ on dipstick or routine urinalysis (UA); if urine
             dipstick or routine analysis is >= 2+, a 24-hour urine collection for protein must
             demonstrate < 1000 mg of protein in 24 hours); these tests must be documented within
             28 calendar days prior to randomization

          -  Patients must not have experienced any arterial thromboembolic events, including but
             not limited to myocardial infarction, transient ischemic attack, cerebrovascular
             accident, or unstable angina, within 6 months prior to randomization

          -  Patients must not have a history of uncontrolled or poorly-controlled hypertension
             (defined as > 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite
             standard medical management

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method (hormonal or barrier method of
             birth control; abstinence) prior to randomization, during the study participation and
             for 4 months after the last dose of protocol treatment; a woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months; in addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures

          -  Patients must not have experienced hemoptysis (defined as bright red blood or >= 1/2
             teaspoon) within 2 months prior to randomization or with radiographic evidence of
             intratumor cavitation or has radiologically documented evidence of major blood vessel
             invasion or encasement by cancer

          -  Patients must not have a prior history of gastrointestinal perforation/fistula (within
             6 months of randomization) or risk factors for perforation

          -  Patients must not have a serious or nonhealing wound, ulcer, or bone fracture within
             28 calendar days prior to randomization

          -  Patients must not be receiving chronic antiplatelet therapy, including aspirin,
             nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and
             others), dipyridamole or clopidogrel, or similar agents within 7 days prior to
             randomization; once-daily aspirin use (maximum dose 325 mg/day) is permitted

          -  Patients must be offered the opportunity to participate in banking of specimens for
             future research

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:From date of registration to date of first documentation of progression or symptomatic, assessed up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Binary proportions will be compared between the arms using either a Fisher?s exact or Chi-squared test at the 1-sided 0.10 level.
Measure:Response rate (complete response, partial response, confirmed and unconfirmed)
Time Frame:Up to 2 years
Safety Issue:
Description:Binary proportions will be compared between the arms using either a Fisher?s exact or Chi-squared test at the 1-sided 0.10 level.
Measure:Disease control rate (complete response, partial response, confirmed or unconfirmed, stable disease)
Time Frame:Up to 2 years
Safety Issue:
Description:Binary proportions will be compared between the arms using either a Fisher?s exact or Chi-squared test at the 1-sided 0.10 level.
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:Binary proportions will be compared between the arms using either a Fisher?s exact or Chi-squared test at the 1-sided 0.10 level.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

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