AzTrials
AzTrials

Metastatic Colorectal CancerPhase 1/2NCT03376659

Durvalumab Plus CV301 With Maintenance Chemotherapy in Metastatic Colorectal or Pancreatic Adenocarcinoma

A Phase 1/2 study testing Durvalumab, CV301 and Capecitabine in people with Metastatic Colorectal Cancer and Colorectal Adenocarcinoma, run by Georgetown University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a dual arm, open label phase I/II study to evaluate the safety and clinical activity of the combination of durvalumab with CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancer whose disease is stable on, or responding to 1st line therapy for metastatic… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab, CV301 and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
8 Aug 2018to 1 Aug 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically proven metastatic pancreatic or colorectal adenocarcinoma with measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1 criteria.
  • Stable on, or responding to 1st line therapy for metastatic disease
  • At least 8 and not more than 16 weeks after initiating 1st line therapy for metastatic disease
  • Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
  • Prior adjuvant chemotherapy is allowed, as long as a minimum of 3 months (for pancreatic cancer) and 6 months (for colorectal cancer) has passed between the completion of adjuvant therapy and the start of first line therapy
  • Disease that is amenable to serial biopsies
Show all 22Show fewer
  • ECOG performance status 0-1
  • Age >= 18 years
  • Blood pressure <160/100 mmHg
  • Adequate hepatic, bone marrow, and renal function:
  • Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9.0 g/dL
  • Renal function: Serum creatinine ≤ 1.5 X upper normal limit of institution's normal range OR creatinine clearance ≥ 40 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. Creatinine clearance should be determined by the Cockcroft-Gault formula (below) or by 24-hour urine collection for determination of creatinine clearance:
  • Males:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
  • Females:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
  • Hepatic function: AST and ALT ≤ 2.5 X the upper normal limit of institution's normal range. Non-fasting bilirubin ≤ 1.5 X the upper normal limit of institution's normal range.
  • Partial Thromboplastin Time (PTT) must be ≤ 1.5 X upper normal limit of institution's normal range and INR (International Normalized Ratio) ≤ 1.5. Subjects on anticoagulant (such as coumadin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator. Due to the drug-drug interaction between warfarin and capecitabine, alternate anticoagulation should be considered.
  • Life expectancy > 12 weeks.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to initiation of treatment AND confirmed prior to initiation of treatment on Day 1.
  • Alternatively, female subjects must be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy).
  • Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consents, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Who cannot join

  • Any prior immunotherapy or vaccine therapy
  • History of active or prior documented autoimmune disease within the past 2 years including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, auto-immune Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the following caveats:
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with Grave's disease, vitiligo, autoimmune alopecia, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible upon consultation with the Study Chairs
  • Patients with questionable diagnosis of autoimmune disease who have never been treated with immunosuppressive regimen and have no ongoing symptoms at the time of enrollment may be eligible after discussion with medical monitor and principle investigator
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNFα antagonists) within 28 days prior to Week 1, Day 1
Show all 43Show fewer
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Study Co-chairs.
  • The use of inhaled, intranasal, ophthalmic or topical corticosteroids is allowed
  • The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension is allowed.
  • Physiologic doses of systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
  • High dose steroid pre-treatment for CT contrast dye allergy is allowed, provided the dose(s) of steroids is(are) given at least 1 week prior to starting the study medications
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
  • o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • Positive test for HIV infection
  • Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening)
  • o Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive IgG antibody to hepatitis B core antigen [anti-HBc] OR negative HBV viral load by PCR) are eligible.
  • Active hepatitis C
  • o Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
  • Active tuberculosis OR known history of previous clinical diagnosis of tuberculosis
  • Severe infections within 4 weeks prior to Week 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • o Any course of oral or IV antibiotics must have been completed at least 2 weeks prior to the first dose of study medications
  • Signs or symptoms of infection within 2 weeks prior to Week 1, Day 1
  • Received oral or IV antibiotics within 2 weeks prior to Week 1, Day 1
  • o Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Administration of a live, attenuated vaccine within 30 days before Week 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • o Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine (e.g., FluMistTM) within 4 weeks prior to Week 1, Day 1 or at any time during the study.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 2 weeks prior to initiation of study treatment, with the following exceptions:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy > 1 week before Week 1, Day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week before Week 1, Day 1)
  • CNS metastases including a history of leptomeningeal carcinomatosis
  • Subjects with uncontrolled seizures
  • The subject has had another active malignancy within the past five years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Questions regarding the inclusion of individual subjects should be directed to the Principle Investigator.
  • Cardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  • Life-threatening visceral disease or other severe concurrent disease
  • Grade ≥2 proteinuria at screening (or known prior)
  • Women who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not employing two highly effective and acceptable forms of contraception throughout their participation in the study and for 90 days after last dose of study drug.
  • Patients concurrently receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or any excipient or any egg products
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase I/II Trial of the PD-L1 Inhibitor, Durvalumab Plus CV301 in Combination With Maintenance Chemotherapy for Patients With Metastatic Colorectal or Pancreatic Adenocarcinoma

This is a dual arm, open label phase I/II study to evaluate the safety and clinical activity of the combination of durvalumab with CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancer whose disease is stable on, or responding to 1st line therapy for metastatic disease. Patients with metastatic colorectal or pancreatic adenocarcinoma who still have an adequate performance status and normal hepatic and renal function will be eligible.

Being tested
Durvalumab, CV301, Capecitabine, Bevacizumab
Keywords
PD-L1
Medical subject headings
Colorectal Neoplasms, Pancreatic Neoplasms

What participants receive

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

  • DurvalumabDrug

    Also called MEDI4736

    750mg IV q2 weeks

  • CV301Biological

    MVA-BN-CV301 (prime) - two priming doses of 1.6 x 109 infectious units/0.5 mL (Inf.U) given subcutaneously (s.c.)

    FPV-CV301 (boost) - dosed at 1 × 109 Inf.U/0.5 mL given s.c.

  • CapecitabineDrug

    Also called Xeloda

    1000mg orally twice a day, Monday - Friday Weekly

  • BevacizumabDrug

    Also called Avastin

    5mg/kg IV q2weeks

Study groups in NCT03376659
Study groupRoleWhat they receive
Phase I - SafetyExperimental* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks (colorectal cancer patients only)
Receives: Drug: Durvalumab; Biological: CV301; Drug: Capecitabine; Drug: Bevacizumab
Phase II - Colorectal Cancer ArmExperimental* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks
Receives: Drug: Durvalumab; Biological: CV301; Drug: Capecitabine; Drug: Bevacizumab
Phase II - Pancreatic Cancer ArmExperimental* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly
Receives: Drug: Durvalumab; Biological: CV301; Drug: Capecitabine

What is being measured

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

  1. Recommended Phase II Dose of Durvalumab

    The Recommended Phase II dose of durvalumab in the combination of durvalumab plus CV301 with maintenance chemotherapy as determined by the Phase I design

    Measured: 6 months

  2. Progression Free Survival (PFS) Colorectal Cancer

    To determine the progression free survival (PFS) of durvalumab plus CV301 in combination with maintenance capecitabine and bevacizumab in patients with metastatic colorectal cancer, whose disease is stable on, or responding to 1st line therapy for metastatic disease

    Measured: 24 months

  3. Progression Free Survival (PFS) Pancreatic Cancer

    To determine the progression free survival rate (PFS) of durvalumab plus CV301 in combination with maintenance capecitabine in patients with metastatic pancreatic cancer, whose disease is stable on, or responding to 1st line therapy for metastatic disease

    Measured: 24 months

Secondary outcomes (6)

  1. Objective Response Rate (ORR)

    ORR is defined as the proportion of patients whose best overall response recorded during treatment is either CR or PR according to the RECIST version 1.1.

    Measured: 1 year

  2. Progression Free Survival (PFS)

    PFS is defined as the time from consenting to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first.

    Measured: 24 months

  3. Overall Survival (OS)

    To determine overall survival, subjects will be followed from time of consent until death (or until study termination). Subject will be followed for survival after discontinuing study medication and after the adverse event collection period has ended.

    Measured: 4 years

  4. Disease Control Rate (DCR)

    DCR is defined as the proportion of patients with a documented CR, PR, or SD at 4 months according to the RECIST version 1.1.

    Measured: 4 months

  5. Tolerability and Safety of the Combination

    Tolerability and safety of the combination as determined by the number of patients with treatment emergent adverse events

    Measured: 2 years

  6. Duration of Response

    The duration of response will also be captured as the time from which a response was first identified, until progression of disease according to the RECIST version 1.1 (or death due to any cause).

    Measured: 1 year

Timeline

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

  1. First posted18 Dec 2017
  2. Study start8 Aug 2018
  3. Primary completion30 Aug 2021
  4. Study completion1 Aug 2023

Why it stopped: Study closed due to lack of enrollment.

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
Sequential
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03376659
Sponsor's protocol ID
2017-1189
Status last verified
Feb 2024
First submitted
20 Nov 2017
Last updated
5 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Durvalumab, CV301 and Capecitabine in people with Metastatic Colorectal Cancer and Colorectal Adenocarcinoma, run by Georgetown University at 1 site 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 22 inclusion and 43 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: stopped early, as of the sponsor's last update on 5 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 10 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase II Dose of Durvalumab (time frame: 6 months). The study lists 3 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 NCT03376659.

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 5 Feb 2024.

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