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Neoplasms MalignantPhase 1NCT01243762

A Study of Dalotuzumab + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + Ridaforolimus Combination Therapies in Participants With Advanced Cancer (MK-0646-027)

A Phase 1 study testing dalotuzumab, MK-0752 and ridaforolimus in people with Neoplasms Malignant, run by Merck Sharp & Dohme LLC.

Terminated

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

Official record
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Trial summary

This is an open-label, two-part study to evaluate the safety and tolerability of combination treatment with dalotuzumab + MK-2206, dalotuzumab + MK-0752, or dalotuzumab + ridaforolimus (MK-8669). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms Malignant
What is being tested?
dalotuzumab, MK-0752 and ridaforolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
No sites listed yet
Study dates
22 Nov 2010to 25 Mar 2013
Phase
Phase 1
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

  • Participants must not have any medical conditions that may impact compliance with the protocol, limit interpretation of study results, or pose an unacceptable medical risk.
  • Participant must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (EGOG) Performance Scale.
  • Participant is able to swallow capsules and has no condition that will preclude swallowing and absorbing oral medications on an ongoing basis.
  • Participant has no history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with prostatic specific antigen (PSA) < 1.0; or has undergone potentially curative therapy with no evidence of that disease for five years, or is deemed at low risk for recurrence by his/her treating physician.
  • Participant has at least one measurable metastatic or recurrent lesion according to Response Criteria in Solid Tumors (RECIST).
  • Part 1:
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  • Participant must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist, or participant is not a candidate for standard therapy, or is unwilling to undergo standard therapy. There is no limit on the number of prior treatment regimens.
  • Part 2:
  • A female participant assigned to the dalotuzumab + MK-2206 or dalotuzumab + ridaforolimus treatment arms must have histologically-confirmed metastatic or recurrent platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist, or participant is not a candidate for standard therapy, or is unwilling to undergo standard therapy. Participants may have received any number of prior treatment regimens.
  • A participant assigned to the dalotuzumab + MK-0752 treatment arms must have histologically-confirmed metastatic or recurrent wild-type KRAS colorectal cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist, or participant is not a candidate for standard therapy, or is unwilling to undergo standard therapy. Participants may have received any number of prior treatment regimens.
  • Participant agrees to provide archival tumor tissue sample or undergo biopsy for analysis of gene expression levels.

Who cannot join

  • Participant has had chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to study Day 1 (6 weeks for nitrosoureas or mitomycin C) or who has not recovered from adverse events due to agents administered more than 4 weeks earlier, or major surgery <4 weeks earlier.
  • Participant is currently participating or has participated in a study with an investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Participants previously treated with a monoclonal antibody will be eligible to participate after a 28 day washout period.
  • Participants with known central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded.
  • Participant has significant or uncontrolled cardiovascular disease, including New York Heart Association (NYHA) Class III-IV heart failure, unstable angina, or a myocardial infarction within the last 6 months.
  • Participant is known to have diabetes that is poorly controlled.
  • Participant is pregnant, breastfeeding, or expecting to conceive or father children during the study.
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  • Participant is known to be human immunodeficiency virus (HIV)-positive.
  • Participant has active Hepatitis B or C infection.
  • Participant has symptomatic ascites or pleural effusion.
  • Participant requires treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for at least two weeks prior to the first dose of study drug.
  • Participant requires treatment with medication(s) that strongly or moderately induce or inhibit cytochrome P450.
  • Participant is using growth hormone or growth hormone inhibitors.
  • Participant requires treatment with therapeutic warfarin.

About this study

Official title: Phase I Parallel Arm Study of MK-0646 (Dalotuzumab) + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + MK-8669 (Ridaforolimus) Doublets (MK-MK Doublets) in Patients With Advanced Cancer

This is an open-label, two-part study to evaluate the safety and tolerability of combination treatment with dalotuzumab + MK-2206, dalotuzumab + MK-0752, or dalotuzumab + ridaforolimus (MK-8669). Part 1 of the study will determine the dose-limiting toxicities (DLTs) observed after administration of each of the combinations at various doses and define the maximum tolerated dose (MTD) of each combination. Part 2 of the study will assess preliminary anti-tumor activity of these combinations (at MTD) in two groups of participants with selected tumor biomarkers: one group with metastatic or recurrent platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and one group with metastatic or recurrent colorectal cancer. The dalotuzumab + ridaforolimus and dalotuzumab + MK-2206 arms will be enriched with female platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer participants. The dalotuzumab + MK-0752 arm will be enriched with metastatic or recurrent wild-type kirsten rat sarcoma (KRAS) colorectal cancer participants.

The primary hypothesis is that the DLTs observed in adult patients with locally advanced or metastatic solid tumors after administration of each of the MK-MK doublets will be dose-dependent to allow for definition of a MTD within each MK-MK doublet.

Being tested
dalotuzumab, MK-0752, ridaforolimus, MK-2206
Keywords
Colorectal cancer, Solid tumors, Ovarian cancer, Fallopian tube cancer, Primary peritoneal cancer
Medical subject headings
Neoplasms, Colorectal Neoplasms, Ovarian Neoplasms, Fallopian Tube Neoplasms

What participants receive

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

  • dalotuzumabDrug

    Also called MK-0646

    Administered intravenously (IV) once weekly in 28-day cycles for a maximum of 6 months of study therapy

  • MK-0752Drug

    Administered orally (PO) weekly in 28-day cycles for a maximum of 6 months of study therapy

  • ridaforolimusDrug

    Also called MK-8669

    Administered PO daily for 5 consecutive days per week in 28-day cycles for a maximum of 6 months of study therapy

  • MK-2206Drug

    Administered PO weekly in 28-day cycles for a maximum of 6 months of study therapy

Study groups in NCT01243762
Study groupRoleWhat they receive
Dalotuzumab 7.5 mg/kg + MK-0752 1800 mgExperimentalParticipants in Part 1 of the study receive dalotuzumab 7.5 mg/kg intravenously (IV) weekly + MK-0752 1800 mg orally (PO) weekly in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: MK-0752
Dalotuzumab 10 mg/kg + MK-0752 1800 mgExperimentalParticipants in Parts 1 and 2 of the study receive dalotuzumab 10 mg/kg IV weekly + MK-0752 1800 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: MK-0752
Dalotuzumab 10 mg/kg + MK-2206 90 mgExperimentalParticipants in Part 1 of the study receive dalotuzumab 10 mg/kg IV weekly + MK-2206 90 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: MK-2206
Dalotuzumab 10 mg/kg + MK-2206 135 mgExperimentalParticipants in Part 1 of the study receive dalotuzumab 10 mg/kg IV weekly + MK- 2206 135 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: MK-2206
Dalotuzumab 10 mg/kg + MK-2206 150 mgExperimentalParticipants in Parts 1 and 2 of the study receive dalotuzumab 10 mg/kg IV weekly + MK- 2206 150 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: MK-2206
Dalotuzumab 10 mg/kg + MK-2206 200 mgExperimentalParticipants in Part 1 of the study receive dalotuzumab 10 mg/kg IV weekly + MK- 2206 200 mg PO weekly in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: MK-2206
Dalotuzumab + RidaforolimusExperimentalParticipants in Part 2 of the study receive dalotuzumab 10 mg/kg IV weekly + ridaforolimus 20 mg PO daily for 5 consecutive days per week in 28-day cycles for a maximum of 6 months of study therapy.
Receives: Drug: dalotuzumab; Drug: ridaforolimus

What is being measured

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

  1. Number of Participants With Dose-limiting Toxicities (DLTs)

    DLTs were defined as follows: 1) non-hematological toxicity ≥Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 except for Grade 3 nausea, vomiting, diarrhea, and/or dehydration; Grade 3 or 4 hyperglycemia; alopecia; inadequately treated hypersensitivity reactions; dalotuzumab infusion-related reactions; Grade 3 transaminases ≤1 week in duration; or clinically non-significant, treatable or reversible lab abnormalities; 2) Grade 4-5 hematologic toxicity, with the exception of Grade 4 neutropenia <6 days in duration; 3) Grade 3 or Grade 4 neutropenia with fever >38.5 degrees C; 4) Grade 4 thrombocytopenia ≤25.0 x 10^9/Liter; 5) drug-related adverse experience leading to a dose modification during Cycle 1; 6) unresolved drug-related toxicity that causes ≥3 week delay of the next scheduled dose of study medication; 7) persistent increases in QTc interval >60 milliseconds from baseline, or clinically significant bradycardia.

    Measured: Cycle 1-28 Days

Secondary outcomes (1)

  1. Number of Participants Whose Best Response is a Partial Response (PR) or Complete Response (CR)

    Best response was determined for the maximum tolerated dose from the start of treatment until disease progression, recurrence, or completion of 6 months of treatment. Lesions were measured by computed tomography (CT) scan or magnetic resonance imaging (MRI). Partial response (PR), defined as a tumor burden decrease of 30%, or complete response (CR) was determined using Response Criteria in Solid Tumors (RECIST) 1.1 for participants with at least one measurable target lesion at baseline.

    Measured: Up to 7 months

Timeline

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

  1. First posted19 Nov 2010 (estimated)
  2. Study start22 Nov 2010
  3. Primary completion4 Dec 2012
  4. Study completion25 Mar 2013

Why it stopped: The study was terminated for business reasons and not due to any safety or efficacy concerns related to dalotuzumab.

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01243762
Sponsor's protocol ID
0646-027
Status last verified
Jul 2018
First submitted
17 Nov 2010
Last updated
16 Aug 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Brana I, Berger R, Golan T, Haluska P, Edenfield J, Fiorica J, Stephenson J, Martin LP, Westin S, Hanjani P, Jones MB, Almhanna K, Wenham RM, Sullivan DM, Dalton WS, Gunchenko A, Cheng JD, Siu LL, Gray JE. A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours. Br J Cancer. 2014 Nov 11;111(10):1932-44. doi: 10.1038/bjc.2014.497. Epub 2014 Oct 7.

    PubMed 25290091

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dalotuzumab, MK-0752 and ridaforolimus in people with Neoplasms Malignant, run by Merck Sharp & Dohme LLC.

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 11 inclusion and 13 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 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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 30 Oct 2017). 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?

Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1-28 Days). 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 NCT01243762, 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 16 Aug 2018.

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