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Mismatch Repair Proficient Colorectal CancerPhase 2DAPPERNCT03851614

Study of DNA Damage, Angiogenesis, and PD-L1 Inhibitors in Advanced Solid Tumors

A Phase 2 study testing Durvalumab, Olaparib and Cediranib in people with Mismatch Repair Proficient Colorectal Cancer and Pancreatic Adenocarcinoma, run by University Health Network, Toronto at 1 site in Canada.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a phase 2, single-centre, randomized, multi-cohort trial of subjects with advanced Mismatch Repair Proficient Colorectal Cancer (MMRp-CRC), Pancreatic Adenocarcinoma (PA), and Leiomyosarcoma (LMS). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab, Olaparib and Cediranib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
1 siteCanada
Study dates
8 Apr 2019to 1 Jan 2027
Phase
Phase 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

  • Signed informed consent
  • Age ≥18
  • ECOG 0-1
  • Have histologically/cytologically-documented, locally-advanced, or metastatic mismatch repair proficient colorectal cancer (MMRp-CRC), pancreatic adenocarcinoma (PA), or leiomyosarcoma (LMS) that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the subject and treating physician
  • Allowable: prior immune-oncology therapy, no maximal limit to the number of prior lines of systemic therapy for advanced or metastatic disease. All prior anti-neoplastic systemic therapy, including immune-oncology, must have a 4 week wash out period. There is no limit to the number of prior anti-neoplastic systemic treatments used before trial enrolment
  • Must have at least 1 tumor site that is amendable to tumor biopsy
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  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided will not be eligible for this study. Subjects who have archival tissue available, not older than 6 months and with no intervening therapies from the day of the biopsy and the initiation of the study, will also be requested to also submit this sample, but are still required to undergo a pre-treatment biopsy.
  • Consent to provide archival tumor tissue for correlative biomarker studies
  • Must have at least 1 tumor site that is RECISTv1.1 measurable by CT or MRI scan. A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable and there is objective evidence of progression following radiotherapy. The biopsy lesion cannot be the same as the target lesion
  • Life expectancy ≥ 16 weeks from proposed first dose date
  • Female subject of childbearing potential should have two negative pregnancy tests as verified by the investigator prior to starting any investigational product therapy: serum pregnancy test at screening and negative serum or urine pregnancy test on Cycle 1, Day 1 prior to treatment, and confirmed prior to each subsequent cycle of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. They must agree to pregnancy testing after the last dose of durvalumab, olaparib or cediranib. This applies even if the subject practices complete abstinence from heterosexual contact
  • Females of childbearing potential who are sexually active with a non-sterilized male partner must agree to practice true abstinence or at least two effective methods of contraception from 28 days prior to starting durvalumab, olaparib or cediranib, and agree to continue using such precautions while taking durvalumab, olaparib or cediranib and for 90 days following the last dose of investigational product(s). Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation and breastfeeding during study participation and for at least 90 days after the final dose of investigational product(s)
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to use at least two effective methods of contraception from Day 1 through 90 days after receipt of the final dose of investigational product(s). In addition, they must refrain from sperm donation for 90 days after the final dose of investigational product(s). Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
  • Adequately controlled thyroid function, with no symptoms of thyroid dysfunction. Elevated thyroid stimulating hormone (TSH) with normal free T3 and free T4 are allowed; subjects on thyroid replacement therapy are allowed
  • Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below. Subjects are not allowed to have received blood transfusion upwards of 28 days prior to study treatment
  • 2.Cohort A
  • Subjects with MMRp-CRC, PA or LMS with the presence or absence of DDR and HRR (homologous recombination repair) genes will be evaluated retrospectively but it is not an eligibility criterion. Prior PARP usage, including olaparib, is excluded, but other DDR pathway inhibitors are allowed
  • 3. Cohort B
  • Prior antiangiogenic treatment is allowed.

Who cannot join

  • All cohorts
  • Involvement in the planning and/or conduct of the study or previous enrolment in the present study
  • Subjects with another malignancy unless curatively treated with no evidence of disease for ≥ 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ, Stage 1, grade 1 endometrial carcinoma. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression. Subjects with previously treated brain metastases may participate provided they are stable, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Subjects with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
  • Measurable disease outside the CNS
  • Only supratentorial metastases allowed
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  • No history of intracranial hemorrhage
  • No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed
  • No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to Day 1 of the study
  • No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
  • Participation in another clinical study with an investigational product during the last 28 days or 5 half-lives prior to study Day 1. Concurrent enrolment in an observational clinical study or the follow-up period of an interventional study is allowed
  • Subjects receiving any systemic chemotherapy, radiotherapy, within 4 weeks from the last dose prior to study treatment.
  • Receiving, or having received during the four weeks prior to study entry, corticosteroids for any reason. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical, or local steroid injections
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
  • Steroids as premedication for hypersensitivity reactions
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of investigational products. Vaccination with a killed vaccine is permitted at any time with consultation with the Principal Investigator
  • Major surgery within 28 days prior to Day 1 of the study or still recovering from prior surgery. Local procedures are allowed if completed at least 24 hours prior to the administration of the first dose of study treatment
  • Any unresolved toxicity NCI CTCAE v5.0 Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, hypothyroidism and the laboratory values defined in the inclusion criteria
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment by the investigation product may be included only after consultation with the Study Physician
  • Any prior unresolved NCI CTCAE v5.0 Grade > 1 irAE while receiving any previous immunotherapy agent with exception of chronic endocrinopathy that is stable on hormone replacement. Subjects who developed Grade 2 or 3 irAE that has since resolved can be discussed with the Principal Investigator.
  • Diagnosis of autoimmune-based rheumatologic disease or clinically significant autoimmune disorders. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment are not excluded. Subjects with hypothyroidism on thyroid supplements are not excluded
  • History of primary immunodeficiency
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
  • History of hypersensitivity to durvalumab, olaparib, cediranib or any excipient
  • Measurable mean value QTcF > 470 msec on resting triplicate ECG within a 24 hour period, or if resting ECG indicates uncontrolled, potentially reversible cardiac conditions, or patients with congenital or family history of long QT syndrome
  • Subjects with relative hypotension (< 100/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of > 20mm Hg
  • A history of poorly controlled hypertension or resting blood pressure > 150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy
  • ---Adequately controlled BP: systolic BP ≤ 140 mmHg and diastolic BP ≤ 90 mmHg in the presence or absence of a stable regimen of antihypertensive therapy.
  • Left ventricular ejection fraction < lower limit of normal (LLN) per institutional guidelines, or <55%, if threshold for normal is not otherwise specified by institutional guidelines, for patients with the following risk factors:
  • Prior or planned treatment with anthracyclines
  • Prior treatment with trastuzumab
  • Prior central thoracic radiation therapy (RT), including exposure of heart to therapeutic doses of ionizing RT
  • History of myocardial infarction within 6 to 12 months prior to randomization
  • Prior history of other significant impaired cardiac function
  • Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection that would preclude adequate absorption of oral drugs
  • History of bowel obstruction within 1 month prior to starting study drugs
  • Subjects unable to swallow orally administered medication
  • Subjects may not have current dependency on IV hydration or total parenteral nutrition
  • Subjects with uncontrolled seizures
  • Active infection requiring systemic antibiotics, antifungal or antiviral drugs
  • Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any subject known to have active tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus, immunocompromised patients, or any patients with a psychiatric disorder that prohibits obtaining informed consent. Subjects who have had adequately treated tuberculosis may be enrolled upon discussion with Principal Investigators. Subjects who have had prior hepatitis B and C and are not carriers, or have been cured with antivirals, are eligible
  • Female subjects who are pregnant, breast-feeding or male or female subjects of reproductive potential who are not employing an effective method of birth control
  • History of myocardial infarction within 6 months prior to registration
  • History of stroke or transient ischemic attack within 6 months prior to registration
  • Heart failure class III or IV
  • Current cardiac arrhythmia requiring concurrent use of anti-arrhythmic drugs
  • History of hypertensive crisis or hypertensive encephalopathy within 3 years prior to registration, or poorly controlled hypertension at time of registration
  • Clinically significant peripheral vascular disease or abdominal aortic aneurysm (> 5 cm) or aortic dissection. If known history of abdominal aortic aneurysm with ≥ 4 cm in diameter, all of the following must be met: an ultrasound within the last 6 months prior to registration will be required to document that it is ≤ 5 cm; subjects must be asymptomatic from the aneurysm; blood pressure must be well controlled as defined in this protocol
  • Unstable angina within 6 months prior to randomization
  • History of hemoptysis or any significant bleeding within the last 1 month prior to enrollment
  • Presence of cavitation of central pulmonary lesion
  • History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation, within the 3 months prior to enrollment
  • Subjects may not have history of bleeding diathesis or coagulopathy. Therapeutic anticoagulation for prior thromboembolic events is permitted but must be discussed with the PI. Subjects requiring two or more anti-thrombotic agents, including anti-platelet agents will be excluded
  • Any condition that would interfere with evaluation of study treatment or interpretation of subject safety or study results.
  • Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
  • Subjects who require blood transfusion within 28 days prior to study entry to maintain Hgb > 100 g/L or platelets > 100 x 109/L. Whole blood transfusions in the last 120 days prior to entry to the study are acceptable, outside of 28 days prior to treatment
  • Cohort A (olaparib, durvalumab)
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting study treatment is 2 weeks
  • Concomitant use of known strong or moderate CYP3A inducers . The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
  • If clinically indicated, subjects may not have features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy.
  • Cohort B (cediranib, durvalumab)
  • A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
  • Concomitant use of known strong cytochrome (CYP) 3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting study treatments is 2 weeks for strong inhibitors, and at least 1 week for moderate inhibitors
  • Concomitant use of known strong CYP3A inducers or moderate CYP3A inducers. The required washout period prior to starting study treatments is 5 weeks for enzalutamide or phenobarbital and 4 weeks for other agents

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumors

This is a phase 2, single-centre, randomized, multi-cohort trial of subjects with advanced Mismatch Repair Proficient Colorectal Cancer (MMRp-CRC), Pancreatic Adenocarcinoma (PA), and Leiomyosarcoma (LMS). Subjects will be stratified based on their primary malignancy and enrolled into one of the following cohorts:

  • Cohort A: olaparib and durvalumab.
  • Cohort B: cediranib and durvalumab.
Read more

Subjects will receive durvalumab through an intravenous line every 4 weeks. If subjects are assigned to the olaparib group, then they will take this pill twice a day continuously. If subjects are assigned to the cediranib group, then they will take this pill once a day for 5 consecutive days, and then have 2 consecutive days off, every week.

Subjects will be enrolled in this trial to evaluate the changes in genomic and immune biomarkers in tumor, peripheral blood and stool samples, in addition to changes in radiomic profiles. About 90 people (45 subjects in each cohort) will be enrolled into this study at the Princess Margaret Cancer Centre.

Read the detailed description

The goal of this study is to evaluate the changes in genomic and immune biomarkers in tumor, peripheral blood and stool samples, in addition to changes in radiomic profiles, of subjects with advanced Mismatch Repair Proficient Coloretal Cancer (MMRp-CRC), Pancreatic Adenocarcinoma (PA), or Leiomyosarcoma (LMS) during combination treatment of durvalumab (inhibitor of PD-L1) with either olaparib (inhibitor of Poly (ADP-ribose) polymerase [PARP]) or cediranib (inhibitor of Vascular Endothelial Growth Factor Receptor [VEGFR] tyrosine kinases).

Being tested
Durvalumab, Olaparib, Cediranib
Medical subject headings
Leiomyosarcoma

What participants receive

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

  • DurvalumabBiological

    Also called Imfinzi

    Durvalumab is a human immunoglobulin G (IgG)1 kappa monoclonal antibody directed against human PD-L1. Durvalumab selectively binds human PD-L1 with high affinity and blocks its ability to bind to PD-1 and cluster of differentiation (CD)80. The fragment crystallizable (Fc) domain of durvalumab contains a triple mutation in the constant domain of the IgG1 heavy chain that reduces binding to the complement component C1q and the Fc gamma receptors responsible for mediating antibody dependent cell mediated cytotoxicity.

  • OlaparibDrug

    Also called Lynparza, AZD2281

    Olaparib (AZD2281) is a potent oral poly Poly (ADP-ribose) Polymerase (PARP) enzyme inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents. Olaparib specifically traps PARP1 and PARP2 enzymes at sites of damaged DNA; the trapped PARP1- or PARP2-DNA complex is cytotoxic and produces clinical response. Although olaparib also binds to PARP3, recent investigations have suggested PARP-3 inhibition does not contribute towards anti-cancer activity.

  • CediranibDrug

    Also called AZD2171

    Cediranib (AZD2171) is a potent oral small molecule Vascular Endothelial Growth Factor (VEGF) receptor tyrosine kinase inhibitor, specifically inhibiting all three VEGF receptors (VEGFR-1, -2 and -3). It has additional inhibitory activity against stem cell factor receptor tyrosine kinase, and less potency against platelet-derived growth factor receptor tyrosine kinases. Cediranib exerts its anti-angiogenic property by competitively inhibiting the ATP binding site on the VEGF receptors.

Study groups in NCT03851614
Study groupRoleWhat they receive
Cohort AExperimentalOlaparib (given orally at a dose of 300 mg twice a day) in combination with Durvalumab (given intravenously at a dose of 1500 mg every 4 weeks)
Receives: Biological: Durvalumab; Drug: Olaparib
Cohort BExperimentalCediranib (given orally at a dose of 20 mg daily, 5 days on 2 days off) in combination with Durvalumab (given intravenously at a dose of 1500 mg every 4 weeks)
Receives: Biological: Durvalumab; Drug: Cediranib

What is being measured

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

  1. Changes in genomic and immune biomarkers that will be measured in the baseline biopsy and the first on-treatment biopsy by applying a log-transformation and the t-test.

    If a departure from the normal distribution will be noticed for the distributions of the CD8 and CD4 then a log-transformation will be applied. The CD8 and CD4 will be compared between responders and non-responders by applying the t-test. Subgroup analysis based on the site will also be attempted.

    Measured: 3 years

Secondary outcomes (6)

  1. Overall response rate (ORR)

    Overall response rate (ORR)

    Measured: 3 years

  2. Clinical benefit rate (CBR)

    Clinical benefit rate (CBR)

    Measured: 3 years

  3. Progression-free survival (PFS)

    Progression-free survival (PFS)

    Measured: 3 years

  4. Overall survival (OS)

    Overall survival (OS)

    Measured: 3 years

  5. Antitumor activity based on iRECIST

    Antitumor activity based on iRECIST

    Measured: 3 years

  6. Incidence of treatment-emergent adverse events (AEs)

    Incidence of treatment-emergent adverse events (AEs)

    Measured: 3 years

Timeline

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

  1. First posted22 Feb 2019
  2. Study start8 Apr 2019
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2027 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03851614
Sponsor's protocol ID
DAPPER
Acronym
DAPPER
Status last verified
Sep 2026
First submitted
31 Jan 2019
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab, Olaparib and Cediranib in people with Mismatch Repair Proficient Colorectal Cancer and Pancreatic Adenocarcinoma, run by University Health Network, Toronto at 1 site in Canada.

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 20 inclusion and 66 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: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. 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 Canada. 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 phase mean?

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?

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?

Changes in genomic and immune biomarkers that will be measured in the baseline biopsy and the first on-treatment biopsy by applying a log-transformation and the t-test. (time frame: 3 years). 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 NCT03851614.

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 Oct 2026.

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