Clinical Trials /

Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers

NCT02639026

Description:

The main purpose of this study is to determine how best to combine hypofractionated radiotherapy, MEDI4736, and tremelimumab and to determine how safe and tolerable hypofractionated radiotherapy, MEDI4736, and tremelimumab are when given together in subjects with metastatic, melanoma, non small cell lung cancer (NSCLC), breast cancer, and pancreatic cancer.

Related Conditions:
  • Breast Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers
  • Official Title: Phase I Trial Of Hypofractionated Radiotherapy In Combination With MEDI4736 And Tremelimumab For Patients With Metastatic Melanoma And Lung, Breast And Pancreatic Cancers

Clinical Trial IDs

  • ORG STUDY ID: UPCC 23915
  • NCT ID: NCT02639026

Conditions

  • Metastatic
  • Melanoma
  • Non Small Cell Lung Cancer (NSCLC)
  • Breast Cancer
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
MEDI4736Cohort 1
TremelimumabCohort 1

Purpose

The main purpose of this study is to determine how best to combine hypofractionated radiotherapy, MEDI4736, and tremelimumab and to determine how safe and tolerable hypofractionated radiotherapy, MEDI4736, and tremelimumab are when given together in subjects with metastatic, melanoma, non small cell lung cancer (NSCLC), breast cancer, and pancreatic cancer.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalSubjects will receive 20 mg/kg MEDI4736 and 1 mg/kg tremelimumab in combination every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses. The total duration of therapy is 12 months. Cohort 1 tests 8 Gy x 3 fractions
  • MEDI4736
  • Tremelimumab
Cohort 2ExperimentalSubjects will receive 20 mg/kg MEDI4736 and 1 mg/kg tremelimumab in combination every 4 weeks for 4 doses, followed by 10 mg/kg MEDI4736 monotherapy every 2 weeks for 18 doses. The total duration of therapy is 12 months. Cohort 2 tests 17 Gy x 1 fraction.
  • MEDI4736
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologically or cytologically confirmed metastatic
             melanoma,metastatic non-small cell lung cancer, metastatic breast cancer, or
             metastatic pancreatic adenocarcinoma relapsed or refractory to therapy as outlined
             below or patients with these malignancies who have declined, are or have become
             unable to tolerate (e.g. progressive chemotherapy-associated peripheral neuropathy),
             or were not eligible for standard therapy: Metastatic melanoma patients at any line
             of therapy, Metastatic non-small cell lung cancer patients who have relapsed or are
             refractory to at least one line of systemic anti-cancer therapy for metastatic
             disease, including cytotoxic chemotherapy or targeted therapy, Metastatic breast
             cancer patients who have relapsed or are refractory to at least one line of systemic
             anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy, hormonal
             therapy, or targeted therapy, Metastatic pancreatic adenocarcinoma who have relapsed
             or are refractory to at least one line of systemic anti-cancer therapy for metastatic
             disease, such as cytotoxic chemotherapy or targeted therapy

          -  At least two measurable lesions (including the index lesion) according to RECIST
             guidelines v1.1

          -  An index lesion measuring between 1cm - 7cm that is amenable to hypofractionated
             radiation therapy at the discretion of the treating radiation oncologist

             o Index lesions in the pancreas are excluded in the second cohort

          -  Age greater than or equal to 18 years

          -  Signed, written informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Adequate hematological function documented within 3 weeks prior to initial treatment
             based on: White blood cell ≥ 2,500 cells/ul without growth factor support, Absolute
             neutrophil count (ANC) ≥ 1,500 cells/ul without growth factor support, Hemoglobin ≥ 9
             g/dL, Platelet count ≥ 100,000 platelets/ul, Adequate hepatic and renal function
             documented within 3 weeks prior to initial treatment based on: Aspartate
             aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of
             normal (ULN). For subjects with liver metastasis, ALT and AST ≤ 5 x ULN, Total
             bilirubin ≤1.5 x ULN except in patients with documented Gilbert's syndrome or liver
             metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/dl, Serum creatinine ≤
             2.0 mg/dL

          -  Full recovery from the acute effects of prior cancer treatments, defined as effects
             having resolved to NCI CTCAE v4.03 Grade 0 or 1 with the exception of alopecia and
             certain laboratory values as listed above. Subjects with irreversible toxicity that
             is not reasonably expected to be exacerbated by MEDI4736 and tremelimumab may be
             included (eg, hearing loss, neuropathy) upon approval of the PI.

          -  For patients with central nervous system (CNS) metastases, metastases must be
             asymptomatic at the time of Day 1 of the study and meet the following criteria:

          -  At least 28 days without progression of CNS metastases as evidenced by magnetic
             resonance imaging (MRI) or computed tomography (CT) after last day of treatment with
             radiation to the CNS metastases

          -  At least 14 days since last dose of corticosteroids

          -  Must not have leptomeningeal disease or cord compression

          -  Females of childbearing potential who are sexually active with a nonsterilized male
             partner must use highly effective method of contraception from the time of screening,
             and must agree to continue using such precautions for 180 days after the final dose
             of MEDI4736 and tremelimumab. Cessation of contraception after this point should be
             discussed with a responsible physician. Periodic abstinence, the rhythm method, and
             the withdrawal method are not acceptable methods of contraception. They must also
             refrain from egg cell donation for 180 days after the final dose of MEDI4736 and
             tremelimumab: Females of childbearing potential are defined as those who are not
             surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete
             hysterectomy) or those who are not post-menopausal (defined as 12 months with no
             menses with postmenopausal gonadotropin levels, luteinizing hormone [LH] and
             follicle-stimulating [FSH], or postmenopausal estradiol levels within the
             postmenopausal range according to local guidelines without an alternative medical
             cause), A highly effective method of contraception is defined as one that results in
             a low failure rate (i.e., less than 1% per year) when used consistently and
             correctly. The acceptable methods of contraception include barrier methods (male
             condom plus spermicide, Copper T intrauterine device, Levonorgesterel-releasing
             intrauterine system) or hormonal methods (implants, hormone shot or injection,
             combined pill, minipill, patch), Nonsterilized males who are sexually active with a
             female partner of childbearing potential must use a highly effective method of
             contraception (as outlined above) from Day 1 through 90 days after receipt of the
             final dose of MEDI4736 and tremelimumab. In addition, they must refrain from sperm
             donation for 90 days after the final dose of investigational product.

        Exclusion Criteria:

          -  Concurrent enrollment in another clinical study, unless in a follow-up period or the
             study is an observational or non-interventional study

          -  Prior treatment with anti-CTLA4, anti-PD-1, or anti-PD-L1 (approved or
             investigational agent)

          -  Concurrent treatment with any anticancer agent, including chemotherapy,
             immunotherapy, or biologic therapy. In breast cancer patients, concurrent use of
             hormonal therapy (but not trastuzumab) is acceptable provided hormonal therapy was
             initiated more than 30 days prior to treatment on this study.

          -  Treatment with any other investigational agent within 3 weeks prior to the first dose
             of MEDI4736 and tremelimumab

          -  Major surgical procedure (as defined by the investigator) within 28 days prior to the
             first dose of MEDI4736 and tremelimumab or still recovering from prior surgery

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of MEDI4736 and tremelimumab with the exceptions of intranasal and inhaled
             corticosteroids, systemic corticosteroids at physiologic doses not to exceed 10
             mg/day of prednisone or equivalent, or steroids used transiently to control contrast
             agent allergies for radiographic studies.

          -  Active or prior documented autoimmune disease (including inflammatory bowel disease,
             diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel
             disease, Wegner syndrome, Hashimoto syndrome) within the past 3 years. Subjects with
             vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment
             (within the past 3 years) are not excluded. Patients with hypothyroidism stable on
             thyroid replacement therapy for the previous 3 months are not excluded.

          -  History of primary immunodeficiency or tuberculosis

          -  History of sensitivity or allergy to monoclonal antibodies or immunoglobulin G

          -  Known true positive results for HIV or known active Hepatitis B (e.g. HBsAg reactive)
             or Hepatitis C (e.g. HCV RNA [qualitative] is detected.

          -  Receipt of a live, attenuated vaccine within 28 days prior to the first dose of
             MEDI4736 and tremelimumab (NOTE: subjects, if enrolled, should not receive live
             vaccine during the study or for 180 days after the last dose of both drugs)

          -  Clinical contraindication to stereotactic body radiotherapy as determined by the
             investigator (e.g., active systemic sclerosis, active inflammatory bowel disease if
             bowel is within radiation field.)

          -  Prior radiotherapy that precludes the proposed treatment with hypofractionated
             radiotherapy

          -  Females who are pregnant, lactating, or intend to become pregnant during the
             participation of the study

          -  Uncontrolled inter-current illness, including, but not limited to, ongoing or active
             infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled
             hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung
             disease, or psychiatric illness/social situations that would limit compliance with
             study requirement or compromise the ability of the subject to give written informed
             consent

          -  Other active invasive malignancy. History of non-invasive malignancies such as
             cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal
             carcinoma in situ of the breast is allowed, as is history of other invasive
             malignancy that is in remission after treatment with curative intent.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of the investigational product or interpretation of subject safety or
             study results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Adverse Events
Time Frame:12 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

September 12, 2016