Clinical Trials /

Cabozantinib in Combination With Durvalumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies (CAMILLA)

NCT03539822

Description:

The investigators propose to evaluate cabozantinib in combination with durvalumab in previously treated patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies after failing the current standard of care chemotherapy options for patients with advanced gastric cancer and other GI malignancies is an area or great unmet need. The investigators believe that modulating the tumor microenvironment with biologic agents like cabozantinib will have synergistic effect when combined with checkpoint-based immunotherapeutics like durvalumab in this patient population. This is a phase 1b, open label, single arm trial looking at safety, tolerability and preliminary efficacy endpoints.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Colorectal Adenocarcinoma
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Cabozantinib in Combination With Durvalumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies (CAMILLA)
  • Official Title: A Phase Ib Trial of Cabozantinib in Combination With Durvalumab (MEDI4736) in Previously Treated Patients With Advanced Gastroesophageal Cancer and Other Gastrointestinal (GI) Malignancies (CAMILLA)

Clinical Trial IDs

  • ORG STUDY ID: IIT-2017-Cabozant+DurvaGI
  • NCT ID: NCT03539822

Conditions

  • Gastric Cancer
  • Esophageal Adenocarcinoma
  • Hepatocellular Carcinoma
  • Colorectal Cancer

Interventions

DrugSynonymsArms
Cabozantinibmulti-tyrosine kinase InhibitorCabozantinib combined with Durvalumab
Durvalumabanti-PD-L1 inhibitorCabozantinib combined with Durvalumab

Purpose

The investigators propose to evaluate cabozantinib in combination with durvalumab in previously treated patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies after failing the current standard of care chemotherapy options for patients with advanced gastric cancer and other GI malignancies is an area or great unmet need. The investigators believe that modulating the tumor microenvironment with biologic agents like cabozantinib will have synergistic effect when combined with checkpoint-based immunotherapeutics like durvalumab in this patient population. This is a phase 1b, open label, single arm trial looking at safety, tolerability and preliminary efficacy endpoints.

Trial Arms

NameTypeDescriptionInterventions
Cabozantinib combined with DurvalumabExperimentalCabozantinib By mouth (PO) once daily on days 1-28 of every 28 day cycle Starting dose will be 20mg Dose escalation will follow the dose escalation table Durvalumab *Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle
  • Cabozantinib
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years

          2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          3. Histologically confirmed diagnosis of any of the following:

               -  Gastric or gastroesophageal junction adenocarcinoma

               -  Esophageal adenocarcinoma

               -  Colorectal adenocarcinoma (CRC)

               -  Hepatocellular carcinoma (HCC)

          4. Patients should have advanced (stage 4) or locally unresectable (stage III) disease.

          5. Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors
             (RECIST) version 1.1

          6. Patients must consent to undergo a required screening/baseline biopsy procedure (and
             potentially another tumor biopsy at time of disease response and progression) for
             correlative testing.

          7. Patients with gastric, gastroesophageal, or esophageal adenocarcinoma must show
             evidence of progression or intolerance to at least two previous standard of care
             systemic therapy.

          8. Patients with CRC must show evidence of progression or intolerance to at least 2
             previous standard of care systemic therapy. Ras wild type patients should fail
             epidermal growth factor receptor (EGFR) monoclonal antibody (panitumumab or cetuximab)
             to be eligible.

          9. Patients with HCC must show evidence of disease progression or intolerance to at least
             1 previous standard of care systemic therapy.

         10. Adequate organ and marrow function.

         11. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients.

         12. Women of child-bearing potential and men with partners of child-bearing potential must
             agree to use the highly effective forms of contraception prior to study entry, for the
             duration of study participation, and for 180 Days post completion of therapy. Men of
             child-bearing potential must not donate sperm while on this study and for 180 Days
             after their last study treatment.

        Exclusion Criteria:

          1. Prior treatment with a programmed death (PD)1 or PD-ligand (L)1 inhibitors or any
             agent directed to another co-inhibitory T cell receptor.

          2. Prior treatment with cabozantinib or other Receptor for hepatocyte growth factor (MET)
             or Dual MET/hepatocyte growth factor (HGF) monoclonal antibodies or MET/HGF tyrosine
             kinase inhibitors (TKIs).

          3. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
             within 6 months before first dose.

          4. Evidence of active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's
             disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis,
             acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or
             gastric outlet obstruction

          5. Inability to swallow tablets.

          6. Uncontrollable ascites or pleural effusion

          7. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
             manifestation

          8. Clinically significant hematuria, hematemesis, or hemoptysis of >0.5 tsp (2.5ml) of
             red blood, or other history of significant bleeding within 12 weeks

          9. Any unresolved toxicity CTCAE Grade ≥2 from previous anticancer therapy

         10. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
             radiation within 4 weeks of the first dose of study drug

         11. Major surgery (eg, Gastrointestinal (GI) surgery, removal or biopsy of brain
             metastasis) within 8 weeks before first dose of study treatment.

         12. Current or prior use of immunosuppressive medication within 14 days before the first
             dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses.

         13. History of allogenic organ transplantation.

         14. Active or prior documented autoimmune or inflammatory disorders

         15. History of active primary immunodeficiency

         16. Active infection including tuberculosis, hepatitis B, hepatitis C, or human
             immunodeficiency virus.

         17. Receipt of live attenuated vaccine within 30 days prior to the first dose.

         18. Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 millimeter of
             mercury (mm Hg) systolic or > 100 mm Hg diastolic despite optimal antihypertensive
             treatment.

         19. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or
             other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary
             embolism) within 6 months before first dose

         20. Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis

         21. Clinically significant disorders that would preclude safe study participation.

         22. History of another primary malignancy except for:

               -  Malignancy treated with curative intent and with no known active disease ≥5 years
                  before the first dose and of low potential risk for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

        24. Concomitant anticoagulation with oral anticoagulants (examples: warfarin, direct
        thrombin) or platelet inhibitors (clopidogrel).

        25. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
        excipients.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:9 months
Safety Issue:
Description:Defined as the highest dose studied for which the observed incidence of dose limiting toxicities (DLT) is less than 33%. Determined per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:Proportion of participants with adverse events (AEs).
Time Frame:18 months
Safety Issue:
Description:Determined per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure:Overall Response Rate (ORR)
Time Frame:18 months
Safety Issue:
Description:Defined as the proportion of patients with overall response to therapy . Overall response is defined as the best response recorded, (including Complete Response (CR) and Partial Response (PR)), from the start of the treatment until the end of treatment. Determined per Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Overall Benefit Rate (OBR)
Time Frame:18 months
Safety Issue:
Description:Defined as the proportion of patients with overall benefit to therapy. Overall benefit is defined as the best response recorded, (including complete Response (CR), Partial Response (PR), and Stable Disease (SD)), from the start of the treatment until the end of treatment. Determined per Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Progression Free Survival (PFS)
Time Frame:24 months
Safety Issue:
Description:Defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first. Determined per Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Overall Survival (OS)
Time Frame:24 months
Safety Issue:
Description:Defined as the time from the start of treatment until death due to any cause. Determined per Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Anwaar Saeed

Trial Keywords

  • Cabozantinib
  • Durvalumab
  • MEDI4736

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