AzTrials
AzTrials

Gastric CancerPhase 1/2CAMILLANCT03539822

Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies

A Phase 1/2 study testing Cabozantinib, Durvalumab and Tremelimumab in people with Gastric Cancer and Esophageal Adenocarcinoma, run by Anwaar Saeed at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The investigators propose to evaluate the safety of drug combinations in patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies for patients with advanced gastric cancer and other GI malignancies is an area of great unmet need. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib, Durvalumab and Tremelimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
117 participants
Where
2 sitesUnited States
Study dates
22 Oct 2018to 30 Jun 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • Histologically confirmed diagnosis of any of the following:
  • Gastric or gastroesophageal junction adenocarcinoma
  • Esophageal adenocarcinoma
  • Colorectal adenocarcinoma (CRC)
Show all 18Show fewer
  • Hepatocellular carcinoma (HCC)
  • Patients should have advanced (stage 4) or locally unresectable (stage III) disease.
  • Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • 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.
  • Patients with gastric, gastroesophageal, or esophageal adenocarcinoma must show evidence of progression or intolerance to at least one previous standard of care systemic therapy.
  • 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.
  • 10. For cohort 3: Patients with HCC must show evidence of disease progression or intolerance to at least 1 previous systemic regimen (not more than 2 lines of prior therapy).
  • 11. For cohort 4: Patients with HCC must be treatment naïve or show evidence of disease progression or intolerance to at least 1 previous systemic regimen (not more than 2 lines of prior therapy).
  • 12. Patients should have known tumor results for microsatellite instability (MSI) or mismatch repair (MMR) proteins. If unknown, analysis will be obtained through local pathology lab using archival tissue if available or the baseline tumor biopsy.
  • 13. Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • 14. Body weight > 66 lbs (30 kg) 15. Adequate organ and marrow function. 16. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
  • 17. 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.

Who cannot join

  • Prior treatment with a Programmed cell death protein 1 (PD1) or (PD-L1) inhibitor, including durvalumab, or anti PD-L2 (HCC and gastric / esophageal cancer patients with prior exposure to these agents are eligible).
  • 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), including crizotinib, foretinib, tivantinib, rilotumumab, and onartuzumab.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
  • Evidence of tumor invading the GI tract, (Defined as T4 primary tumor in patients with gastric, gastroesophageal and esophageal adenocarcinoma and CRC).
  • Gastric or esophageal varices that are untreated or incompletely treated with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible.
  • 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.
Show all 34Show fewer
  • Inability to swallow tablets.
  • Uncontrollable ascites or pleural effusion.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Clinically significant hematuria, hematemesis, or hemoptysis of >0.5 tsp (2.5ml) of red blood, or other history of significant bleeding within 12 weeks.
  • Any sign indicative of pulmonary hemorrhage within 3 months.
  • Lesions invading any major blood vessels. HCC subjects with lesions invading the hepatic portal vasculature are eligible.
  • Any unresolved toxicity CTCAE Grade ≥2 from previous anticancer therapy
  • 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
  • Major surgery (eg, Gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment.
  • 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.
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders
  • History of active primary immunodeficiency
  • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. HCC patients with hepatitis B or C infection are allowed per protocol specific criteria.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose.
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 millimeter of mercury (mm Hg) systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
  • 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. Participants with a diagnosis of deep venous thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with Low Molecular Weight Heparin (LMWH) for at least 2 weeks before first dose.
  • Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Clinically significant disorders that would preclude safe study participation.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent/ resection and with no known active disease before the first dose of investigational product (IP) 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 (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
  • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
  • Low-dose (prophylactic) low molecular weight heparins (LMWH) are permitted.
  • Anticoagulation with therapeutic doses of LMWH is allowed in subjects with no known brain metastases, clinically significant hemorrhage, or complications from a thromboembolic event on the anticoagulation regimen (subjects with HCC must also have a screening platelet count >100,000/μl), and who have been on a stable dose of LMWH for at least 1 week before first dose.
  • 25. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Debra Diecks, RN contact

4126238364

diecksda@upmc.edu

Clare Grzejka, RN contact

4126234891

grzejkac@upmc.edu

United States2 sites, 1 recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Debra Diecks, RN, 4126238364, diecksda@upmc.edu

    Clare Grzejka, RN, 412-623-4891, grzejkac@upmc.edu

    Recruiting

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

    Terminated

Other trials in United States

About this study

Official title: A Phase I/II Trial of Cabozantinib in Combination With Durvalumab (MEDI4736) With or Without Tremelimumab in Patients With Advanced Gastroesophageal Cancer and Other Gastrointestinal (GI) Malignancies (CAMILLA)

The investigators propose to evaluate the safety of drug combinations in patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies for patients with advanced gastric cancer and other GI malignancies is an area of 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 I/II, open label, multi-cohort trial looking at safety, tolerability and efficacy endpoints.

Keywords
Cabozantinib, Durvalumab, Tremelimumab
Medical subject headings
Stomach Neoplasms, Adenocarcinoma Of Esophagus, Carcinoma, Hepatocellular, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called multi-tyrosine kinase Inhibitor

    by mouth

  • DurvalumabDrug

    Also called anti-Programmed cell death protein 1 (PD-L1) inhibitor

    infusion

  • TremelimumabDrug

    Also called Anti-CTLA4 inhibitor

    infusion

Study groups in NCT03539822
Study groupRoleWhat they receive
Cabozantinib plus Durvalumab (Gastric & esophageal cancer cohort)ExperimentalCabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab *Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle
Receives: Drug: Cabozantinib; Drug: Durvalumab
Cabozantinib plus Durvalumab (Colorectal cancer cohort)ExperimentalCabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab *Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle
Receives: Drug: Cabozantinib; Drug: Durvalumab
Cabozantinib plus Durvalumab (Hepatocellular carcinoma cohort)ExperimentalCabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab *Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle
Receives: Drug: Cabozantinib; Drug: Durvalumab
Cabozantinib plus Durvalumab plus Tremelimumab (Hepatocellular carcinoma cohort)ExperimentalCabozantinib * By mouth (PO) once daily on days 1-28 of every 28 day cycle * Dose will be 40mg Durvalumab *Flat dose of 1500mg intravenous (IV) Infusion on day 1 of every 28 day cycle Tremelimumab *Single dose of 300mg intavenous (IV) infusion on day 1 of cycle 1
Receives: Drug: Cabozantinib; Drug: Durvalumab; Drug: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I- Maximum Tolerated Dose (MTD)

    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.

    Measured: 9 months

  2. Phase II- Overall Response Rate (ORR)

    Defined as the proportion of participants best response to treatment. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Every 8 weeks for 12 months

Secondary outcomes (4)

  1. Proportion of participants with adverse events (AEs).

    Determined per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: 18 months

  2. Overall Benefit Rate (OBR)

    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. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameterswhileonstudy.

    Measured: 18 months

  3. Progression Free Survival (PFS)

    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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Measured: 24 months

  4. Overall Survival (OS)

    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.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2018
  2. Study start22 Oct 2018
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Phase II has 4 disease cohorts, the first 3 with 29 patients each, the 4th cohort for advanced HCC patients with 24 patients, preceded by a 6-9 patient safety lead-in.
Masking
None (open label)
Enrolment
117 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03539822
Sponsor's protocol ID
HCC 22-192
Acronym
CAMILLA
Status last verified
Jan 2026
First submitted
16 May 2018
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Saeed A, Park R, Pathak H, Al-Bzour AN, Dai J, Phadnis M, Al-Rajabi R, Kasi A, Baranda J, Sun W, Williamson S, Chiu YC, Osmanbeyoglu HU, Madan R, Abushukair H, Mulvaney K, Godwin AK, Saeed A. Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort. Nat Commun. 2024 Feb 20;15(1):1533. doi: 10.1038/s41467-024-45960-2.

    PubMed 38378868

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cabozantinib, Durvalumab and Tremelimumab in people with Gastric Cancer and Esophageal Adenocarcinoma, run by Anwaar Saeed at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Debra Diecks, RN (4126238364, diecksda@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I- Maximum Tolerated Dose (MTD) (time frame: 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03539822, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in