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

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ClinicalTrials.gov Identifier: NCT03539822
Recruitment Status : Recruiting
First Posted : May 28, 2018
Last Update Posted : September 18, 2018
Sponsor:
Collaborators:
AstraZeneca
Exelixis
Information provided by (Responsible Party):
Anwaar Saeed, University of Kansas Medical Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastric Cancer Esophageal Adenocarcinoma Hepatocellular Carcinoma Colorectal Cancer Drug: Cabozantinib Drug: Durvalumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 14, 2018
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cabozantinib combined with Durvalumab

Cabozantinib

  • 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

Drug: Cabozantinib
by mouth
Other Name: multi-tyrosine kinase Inhibitor

Drug: Durvalumab
infusion
Other Name: anti-PD-L1 inhibitor




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 9 months ]
    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 :
  1. Proportion of participants with adverse events (AEs). [ Time Frame: 18 months ]
    Determined per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  2. Overall Response Rate (ORR) [ Time Frame: 18 months ]
    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.

  3. Overall Benefit Rate (OBR) [ Time Frame: 18 months ]
    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.

  4. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    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.

  5. Overall Survival (OS) [ Time Frame: 24 months ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03539822


Contacts
Contact: Kerry Hepler 913-945-7552 ctnursenav@kumc.edu
Contact: Anwaar Saeed, MD asaeed@kumc.edu

Locations
United States, Kansas
The University of Kansas Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Kerry Hepler    913-945-7552    ctnursenav@kumc.edu   
Principal Investigator: Anwaar Saeed, MD         
Sponsors and Collaborators
Anwaar Saeed
AstraZeneca
Exelixis
Investigators
Principal Investigator: Anwaar Saeed, MD The University of Kansas Cancer Center

Responsible Party: Anwaar Saeed, Assistant Professor, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT03539822     History of Changes
Other Study ID Numbers: IIT-2017-Cabozant+DurvaGI
First Posted: May 28, 2018    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anwaar Saeed, University of Kansas Medical Center:
Cabozantinib
Durvalumab
MEDI4736

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Carcinoma, Hepatocellular
Stomach Neoplasms
Esophageal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Liver Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs