Clinical Trials /

A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

NCT01975831

Description:

This is a multicenter, open-label, study with a standard 3+3 dose-escalation phase, followed by an expansion phase in subjects with solid tumors

Related Conditions:
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Ovarian Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab
  • Official Title: A Phase 1 Study to Evaluate the Safety and Tolerability of Anti-PD-L1, MEDI4736, in Combination With Tremelimumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: LUD2013-003
  • NCT ID: NCT01975831

Conditions

  • Breast Cancer
  • Ovarian Cancer
  • Colorectal Cancer
  • Cervical Cancer
  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
MEDI4736DurvalumabMEDI4736 & Tremelimumab Treatment
TremelimumabMEDI4736 & Tremelimumab Treatment

Purpose

This is a multicenter, open-label, study with a standard 3+3 dose-escalation phase, followed by an expansion phase in subjects with solid tumors

Trial Arms

NameTypeDescriptionInterventions
MEDI4736 & Tremelimumab TreatmentExperimentalMEDI4736 and Tremelimumab will be administered by IV infusion
  • MEDI4736
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically- or cytologically-confirmed ovarian cancer, colorectal cancer,
             non-triple negative breast cancer, renal cell carcinoma and cervical cancer, with at
             least one lesion measurable by irRC not previously irradiated.

          2. Failed to respond to or relapsed following standard treatment, or declined or was not
             eligible for standard treatment.

          3. ECOG performance status of 0-2.

          4. Anticipated lifespan greater than 6 month.

          5. At the time of day 1 of the study, subjects with brain metastases must be asymptomatic
             for at least 4 weeks and:

               -  at least 8 weeks without tumor progression after any whole brain radiotherapy

               -  at least 4 weeks since craniotomy and resection or stereotactic radiosurgery

               -  at least 3 weeks without new brain metastases as evidenced by MRI/CT

          6. Adequate organ and marrow function , as defined below:

               -  Hemoglobin ≥ 9 g/dL

               -  Absolute Neutrophil Count ≥ 1500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Total bilirubin within normal ranges unless associated with hepatobiliary
                  metastases or Gilbert syndrome, then total bilirubin ≤ 2 x ULN

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
                  unless associated with hepatic metastases, then ALT and AST ≤ 5 x ULN

               -  Creatinine ≤ 2.0 mg/dL

          7. Have been informed of other treatment options.

          8. Age ≥18 years.

          9. Able and willing to give valid written informed consent.

         10. Able and willing to give valid written consent for archival tumor samples

         11. Able and willing to give valid written consent for biopsy samples (subjects in the
             expansion phase only).

        Exclusion Criteria:

          1. Prior exposure to tremelimumab or MEDI4736 or other anti-CTLA-4, anti-PD-1, anti-PDL1
             antibodies

          2. History of severe allergic reactions to any unknown allergens or any components of the
             study drugs.

          3. Active or prior autoimmune disease except for autoimmune thyroiditis or vitiligo.

          4. Any prior Grade ≥ 3 immune-related adverse event (irAE) or any prior
             corticosteroid-refractory irAE.

          5. Known active or chronic viral hepatitis or history of any type of hepatitis within the
             last 6 months.

          6. History of sarcoidosis syndrome.

          7. Active or history of inflammatory bowel disease (colitis, Crohn's), diverticulitis,
             irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal
             conditions associated with diarrhea. Active or history of systemic lupus erythematosus
             or Wegener's granulomatosis.

          8. Metastatic disease to the central nervous system for which other therapeutic options,
             including radiotherapy, may be available.

          9. Known immunodeficiency or active HIV.

         10. Other active serious illnesses (e.g., serious infections requiring antibiotics).

         11. If a subject previously received investigational treatment, the last dose of
             investigational treatment was administered within 4 weeks of Day 1 of the study or
             adverse event(s) attributable to investigational treatment have not resolved to Grade
             1 or better.

         12. Major surgical procedure (as defined by the investigator) within 30 days prior to Day
             1 or still recovering from prior surgery.

         13. Mental impairment that may compromise the ability to give informed consent and comply
             with the requirements of the study.

         14. Lack of availability for immunological and clinical follow-up assessments.

         15. Women who are breast feeding or pregnant as evidenced by positive serum pregnancy
             test.

         16. Females of childbearing potential who are sexually active with a nonsterilized male
             partner must use 2 methods of effective contraception from screening, and must agree
             to continue using such precautions for 6 months after the final dose of
             investigational product; cessation of birth control after this point should be
             discussed with a responsible physician. Periodic abstinence, the rhythm method, and
             the withdrawal method are not acceptable methods of birth control.

             Females of childbearing potential are defined as those who are not surgically sterile
             (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or
             postmenopausal (defined as 12 months with no menses without an alternative medical
             cause). Nonsterilized males who are sexually active with a female partner of
             childbearing potential must use 2 acceptable methods of effective contraception from
             Day 1 and for 6 months after receipt of the final dose of investigational product.

         17. Any condition that, in the clinical judgment of the treating physician, is likely to
             prevent the subject from complying with any aspect of the protocol or that may put the
             subject at unacceptable risk.
      
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:Up to 1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736 and Tremelimumab
Time Frame:Up to 15 months
Safety Issue:
Description:
Measure:Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)
Time Frame:Up to 15 months
Safety Issue:
Description:
Measure:Tumor Response by the Immune-related Response Criteria
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Tumor Response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Progression-free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Ludwig Institute for Cancer Research

Trial Keywords

  • Non Triple Negative Breast Cancer

Last Updated

February 14, 2017