Back to results

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients With Metastatic Cancer in Response After 6 Months of Standard IO (MOIO)

Primary Purpose

Lung Cancer Metastatic, Renal Cell Carcinoma, Head and Neck Cancer

Status

Recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Reduced dose intensity of IO

About this trial

This is an interventional treatment trial for Lung Cancer Metastatic focused on measuring Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have signed a written informed consent form prior to any trial specific procedures.
Patient aged ≥18 years old.
Initial metastatic disease histologically confirmed including: lung cancer, renal cell cancer, head and neck cancer, bladder cancer, triple negative breast cancer, Merkel cancer, hepatocellular carcinoma, and melanoma.
Patients in partial or complete response after 6 months of standard immunotherapy (whatever the line of therapy) according to the RECIST (confirmed by local radiological assessment). For metastatic melanoma only patients in partial response.
Eligible to maintain the same standard IO treatment.
Patient with Eastern cooperative oncology group (ECOG) performance status ≤1.
Patients with brain metastases are allowed, provided they are stable according to the following definitions: treated with surgery or stereotactic radiosurgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases.
Patients treated by IO previously combined with chemotherapy are allowed.
Patients with Tyrosine Kinase Inhibitor (TKI)-IO or pemetrexed-IO or bevacizumab-IO are allowed.
Evidence of post-menopausal status, or negative urinary or serum pregnancy test for pre-menopausal patients.
Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use adequate contraception method for the duration of the study treatment and after completing treatment according to the most recent version of the IO Summary of product characteristics (SmPC).
Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.
Patient must be affiliated to a Social Security System.

Exclusion Criteria:

Metastatic melanoma in complete response.
Metastatic renal cell carcinoma with International Metastatic Renal Cell Carcinoma Database (IMDC) favourable-risk treated TKI/IO combination.
Hematologic malignancies (leukaemia, myeloma, lymphoma…)
Active infection requiring systemic therapy.
Patients enrolled in another therapeutic study within 30 days before the inclusion in and during MOIO study.
Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study.
Person deprived of their liberty or under protective custody or guardianship.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Experimental arm

Control arm

Arm Description

Reduced dose intensity of IO: IO will be administered every 3 months (at the same dose levels) until disease progression, unacceptable toxicity, death or patient's choice or investigator's decision

Standard IO: Continuation of IO at the same dose levels and rhythmicity until disease progression, unacceptable toxicity, death or patient's choice.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

Secondary Outcome Measures

Cost-effectiveness analysis of the proposed therapeutic strategy

Incremental cost-effectiveness ratio (ICER) expressed as a cost per quality-adjusted life year (QALY) gained at 36 months.

Immune progression-free survival (iPFS)

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse (Immune disease progression (iPD)). iPD will be determined locally by the investigator through the use of iRECIST in case of lesions identified at Baseline.

Objective response rate (ORR)

Objective response rate (ORR) defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1 at 12 and 24 months post-randomization.

Overall survival (OS)

The overall survival is the length of time from randomization that patients enrolled in the study are still alive.

Duration of response (DoR)

Duration of response (DoR) defined as the time from randomization to first documented response until disease progression or death, whichever occurs first.

Quality of life questionnaire - Core 30 (QLQ-C30)

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

The Developed 5-level version of EQ-5D (EQ-5D-5L) questionnaire

Developed by the EuroQol group, the self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials consists of a descriptive system and a visual analogue scale (VAS). The EQ-5D-5L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each dimension has 5 levels. This questionnaire provide a 5-digit score which generate a health state profile. The VAS records the patient's self-rated health on a vertical visual analogue scale where the score range from 100 (Best imaginable health state) to 0 (Worst imaginable health state). The VAS is used as a quantitative measure of health outcome that reflects the patient's own judgement.

Hospital anxiety and depression scale (HADS)

The HADS is a 14 items questionnaire: 7 items related to anxiety and 7 items related to depression scored on a scale. Scores for items in each subscale of the HADS are summed to produce an anxiety score (HADS-A) or a depression score (HADS-D), or can be added to produce a total score corresponding to emotional distress (HADS-T). Each item is rated on a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), for a total score ranging from 0-21 for each subscale. The entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress.

Fear of relapse questionnaire

The Fear of relapse questionnaire is a self-reported questionnaire aiming to better understand how these concerns of fear of relapse by patients manifest themselves. The questionnaire contains 32 items rated on a five-point Likert-type scale (0 = "never", 1 = "seldom ", 2 = "sometimes", 3 = "often", and 4 = "always"). For all items, higher scores indicate more severe fear of relapse.

Safety profile

The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

Full Information

NCT ID

NCT05078047

First Posted

September 30, 2021

Last Updated

August 29, 2023

Sponsor

UNICANCER

1. Study Identification

Unique Protocol Identification Number

NCT05078047

Brief Title

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients With Metastatic Cancer in Response After 6 Months of Standard IO

Acronym

MOIO

Official Title

Randomized Phase III Trial of Standard Immunotherapy (IO) by Checkpoint Inhibitors, Versus Reduced Dose Intensity of IO in Patients With Metastatic Cancer in Response After 6 Months of Standard IO

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 8, 2022 (Actual)

Primary Completion Date

March 7, 2025 (Anticipated)

Study Completion Date

March 7, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNICANCER

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Immunotherapy (IO), such as treatment with anti-PD-1, PD-L1, or CTLA-4 inhibitors, is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. However, the optimal duration of immunotherapies is currently unknown. Our hypothesis is that a reduced dose intensity of IO could be as effective as the current standard treatment in term of prevention of the disease progression. If proved right, this study will have a positive medico-economic impact by reduction of the costs associated with the treatment and the toxicity, and an increase of the patients' quality of life.

Detailed Description

Immunotherapy (IO) is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. For currently approved immunotherapies such as PD-1 / PD-L1 inhibitors and anti-CTLA-4, the rhythm and duration of treatment are recommended until disease progression or unacceptable toxicity. However, the optimal duration of these treatments is currently unknown. No major dose-dependent effect of anti-PD-1 have been observed and whether the frequency of infusion of IO could improve response or maintain efficacy. Moreover, phase I studies have shown that saturation of the target (PD-1 or PD-L1) can persist far beyond the serum half-life of the IO and 3-monthly infusions of an anti-PD-1 antibody could potentially generate the same level of activity as infusions administered every 2 weeks. In silico modeling studies have suggested that alternate scheduling with IO couldn't compromise the efficacy of the treatment. Indeed, prolonged half-lives of IO drugs, time-varying clearance plus plasma concentrations far above the threshold associated with maximal target-engagement, suggest that the rhythm of administration of IO could be slowed down. Without substantial international data for responding patients, apart metastatic melanoma in complete response, patients and physicians are afraid of stopping treatment, by fear of relapse. Over-treatment with IO may be toxic and inefficient. The rising cost of cancer care in the era of immunotherapy is of great concern for public and private payers around the world. Chronic administration has important consequences for patients and health systems, with multiple medical visits and the risk of chronic, progressive and sometimes fatal toxicities induced by immunotherapy. This is a pragmatic and strategic study challenging the routine practice which compares for the first time in a randomized phase III study, the standard administration of IO versus the same agent administered each three months in patients with metastatic cancer in partial or complete response after 6 months of standard IO ( except melanoma in CR). If our hypothesis of non-inferiority of PFS with a reduced dose intensity of IO is verified, this could replace standard treatment and have a positive medico-economic impact, allowing, on the one hand, a reduction of the costs associated with the treatment and the toxicity, and on the other hand, an increase of the patients' quality of life.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer Metastatic, Renal Cell Carcinoma, Head and Neck Cancer, Bladder Cancer, Triple Negative Breast Cancer, Merkel Cell Carcinoma, Hepatocellular Carcinoma, Melanoma

Keywords

Immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Patients will be randomized 1:1 into two arms: • Experimental arm: Reduced dose intensity of IO IO will be administered every 3 months (at the same dose levels) until disease progression, unacceptable toxicity, death or patient's choice or investigator's decision. • Control arm: Standard IO Continuation of IO at the same dose levels and rhythmicity until disease progression, unacceptable toxicity, death or patient's choice. Random allocation will be stratified by tumour type, by response status (partial response versus complete response) evaluated 6 months after the initiation of standard IO, by treatment line (first line vs others), and by type of IO

Masking

None (Open Label)

Allocation

Randomized

Enrollment

646 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental arm

Arm Type

Experimental

Arm Description

Reduced dose intensity of IO: IO will be administered every 3 months (at the same dose levels) until disease progression, unacceptable toxicity, death or patient's choice or investigator's decision

Arm Title

Control arm

Arm Type

No Intervention

Arm Description

Standard IO: Continuation of IO at the same dose levels and rhythmicity until disease progression, unacceptable toxicity, death or patient's choice.

Intervention Type

Drug

Intervention Name(s)

Reduced dose intensity of IO

Intervention Description

After 6 months of treatment with standard IO, IO will be administered every 3 months (at the same dose levels) until disease progression, unacceptable toxicity, death or patient's choice or investigator's decision

Primary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

Time Frame

From randomization to disease progression or death, up to 3 years

Secondary Outcome Measure Information:

Title

Cost-effectiveness analysis of the proposed therapeutic strategy

Description

Incremental cost-effectiveness ratio (ICER) expressed as a cost per quality-adjusted life year (QALY) gained at 36 months.

Time Frame

3 years

Title

Immune progression-free survival (iPFS)

Description

Time Frame

From randomization to disease progression or death, up to 3 years

Title

Objective response rate (ORR)

Description

Time Frame

From randomization to 12 and 24 months post-randomization

Title

Overall survival (OS)

Description

The overall survival is the length of time from randomization that patients enrolled in the study are still alive.

Time Frame

From randomization to death from any cause, up to 3 years

Title

Duration of response (DoR)

Description

Duration of response (DoR) defined as the time from randomization to first documented response until disease progression or death, whichever occurs first.

Time Frame

From randomization to disease progression or death, up to 3 years

Title

Quality of life questionnaire - Core 30 (QLQ-C30)

Description

Time Frame

At inclusion visit (pre-randomization) and 3, 6, 9, 12, 15, 18, 24, and 36 months post-randomization

Title

The Developed 5-level version of EQ-5D (EQ-5D-5L) questionnaire

Description

Time Frame

At inclusion visit (pre-randomization) and 3, 6, 9, 12, 15, 18, 24, and 36 months post-randomization

Title

Hospital anxiety and depression scale (HADS)

Description

Time Frame

At inclusion visit (pre-randomization) and 3, 6, 9, 12, 15, 18, 24, and 36 months post-randomization

Title

Fear of relapse questionnaire

Description

Time Frame

At inclusion visit (pre-randomization) and 3, 6, 9, 12, 15, 18, 24, and 36 months post-randomization

Title

Safety profile

Description

Time Frame

At 12 months and 3 years post-randomization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have signed a written informed consent form prior to any trial specific procedures. Patient aged ≥18 years old. Initial metastatic disease histologically confirmed including: lung cancer, renal cell cancer, head and neck cancer, bladder cancer, triple negative breast cancer, Merkel cancer, hepatocellular carcinoma, and melanoma. Patients in partial or complete response after 6 months of standard immunotherapy (whatever the line of therapy) according to the RECIST (confirmed by local radiological assessment). For metastatic melanoma only patients in partial response. Eligible to maintain the same standard IO treatment. Patient with Eastern cooperative oncology group (ECOG) performance status ≤1. Patients with brain metastases are allowed, provided they are stable according to the following definitions: treated with surgery or stereotactic radiosurgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases. Patients treated by IO previously combined with chemotherapy are allowed. Patients with Tyrosine Kinase Inhibitor (TKI)-IO or pemetrexed-IO or bevacizumab-IO are allowed. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for pre-menopausal patients. Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use adequate contraception method for the duration of the study treatment and after completing treatment according to the most recent version of the IO Summary of product characteristics (SmPC). Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up. Patient must be affiliated to a Social Security System. Exclusion Criteria: Metastatic melanoma in complete response. Metastatic renal cell carcinoma with International Metastatic Renal Cell Carcinoma Database (IMDC) favourable-risk treated TKI/IO combination. Hematologic malignancies (leukaemia, myeloma, lymphoma…) Active infection requiring systemic therapy. Patients enrolled in another therapeutic study within 30 days before the inclusion in and during MOIO study. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study. Person deprived of their liberty or under protective custody or guardianship.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clotilde SIMON

Phone

+33 (0) 1 73 79 79 11

c-simon@unicancer.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gwenaëlle GRAVIS-MESCAM, MD

Organizational Affiliation

Institut Paoli-Calmettes, Marseille

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut de cancérologie de l'Ouest

City

Angers

ZIP/Postal Code

49055

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Elouen BOUGHALEM

Facility Name

Clinique Sainte Catherine

City

Avignon

ZIP/Postal Code

84918

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Werner HILGERS

Facility Name

Centre Hospitalier de la Côte Basque

City

Bayonne

ZIP/Postal Code

64109

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Louis FRANCOIS

Facility Name

CHU Besançon

City

Besançon

ZIP/Postal Code

25030

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hamadi ALMOTLAK

Facility Name

Centre François Baclesse

City

Caen

ZIP/Postal Code

14076

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pierre-Emmanuel BRACHET

Facility Name

Centre Jean Perrin

City

Clermont-Ferrand

ZIP/Postal Code

63000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Maureen BERNADACH

Facility Name

Centre Hospitalier Intercommunal

City

Créteil

ZIP/Postal Code

94010

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Isabelle MONNET

Facility Name

CHU Henri Mondor

City

Créteil

ZIP/Postal Code

94010

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Carolina SALDANA

Facility Name

Centre Georges François Leclerc

City

Dijon

ZIP/Postal Code

21079

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alice HERVIEU

Facility Name

Clinique Chenieux

City

Limoges

ZIP/Postal Code

87000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sabrina FALKOWSKI

Facility Name

Hospices Civils de Lyon

City

Lyon

ZIP/Postal Code

69310

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Denis MAILLET

Facility Name

Hôpital La Timone -APHM

City

Marseille

ZIP/Postal Code

13385

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean-Laurent DEVILLE

Facility Name

Centre Antoine Lacassagne

City

Nice

ZIP/Postal Code

06189

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Delphine BORCHIELLINI

Facility Name

Institut Curie

City

Paris

ZIP/Postal Code

75005

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christophe LE TOURNEAU

Facility Name

Hôpital Saint Louis

City

Paris

ZIP/Postal Code

75010

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hélène GAUTHIER

Facility Name

Hôpital Pitié Salpêtrière

City

Paris

ZIP/Postal Code

75013

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Luca CAMPEDEL

Facility Name

Hôpital Européen Georges Pompidou

City

Paris

ZIP/Postal Code

75015

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yann VANO

Facility Name

CHU Poitiers

City

Poitiers

ZIP/Postal Code

86000

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nicolas ISAMBERT

Facility Name

Insitut Godinot

City

Reims

ZIP/Postal Code

51726

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amélie LEMOINE

Facility Name

Centre Eugene Marquis

City

Rennes

ZIP/Postal Code

35042

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laurence CROUZET

Facility Name

Institut Curie

City

Saint-Cloud

ZIP/Postal Code

92210

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christophe LE TOURNEAU

Facility Name

Institut de cancérologie de l'Ouest

City

Saint-Herblain

ZIP/Postal Code

44805

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Judith RAIMBOURG

Facility Name

ICANS

City

Strasbourg

ZIP/Postal Code

67200

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Philippe BARTHELEMY

Facility Name

Hôpital Foch

City

Suresnes

ZIP/Postal Code

92151

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Raffaele RATTA

Facility Name

IUCT

City

Toulouse

ZIP/Postal Code

31059

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Iphigénie KORAKIS

Facility Name

CHU Bretonneau

City

Tours

ZIP/Postal Code

37044

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mathilde CANCEL

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

IPD Sharing Time Frame

The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

IPD Sharing Access Criteria

Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Learn more about this trial

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients With Metastatic Cancer in Response After 6 Months of Standard IO

We'll reach out to this number within 24 hrs

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients With Metastatic Cancer in Response After 6 Months of Standard IO (MOIO)

Lung Cancer Metastatic, Renal Cell Carcinoma, Head and Neck Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial