Anti-PD-1 +/- RT for MSI-H Solid Tumors

NCT ID: NCT04001101

Last Updated: 2021-11-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-10
• Study Completion Date: 2021-11-17

Brief Summary

To determine if the out-of-field ORR is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. Determine the rates of in-field tumor control, disease control (stable disease, partial response, complete response), durability of disease response, progression-free survival, overall survival, and to assess quality of life and toxicity. Determine the chronology and profile of the radiation-associated immune response.

Detailed Description

This is a randomized phase II study with a primary objective to compare the objective response rate (ORR) for anti-PD-1 therapy alone versus anti-PD-1 therapy and limited metastatic site radiation, in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic solid tumors. The anti-PD-1 agent, pembrolizumab, received recent FDA accelerated approval for the use in patients with metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment or without satisfactory alternative treatment options. FDA approval for pembrolizumab was based on the results of five multi-cohort, multi-center, single-arm trials, which together showed an ORR of 39.6% among 149 patients with MSI-H/dMMR cancers. Importantly, there is mounting preclinical and clinic evidence supporting the safety and efficacy of combining radiation therapy with systemic immunotherapy, although no prospective comparative data, to the best of our knowledge. In this study, the investigators will focus on patients with MSI-H/dMMR tumors, given their baseline responsiveness to immune checkpoint inhibition, and test the hypothesis that ORR will be improved with radiation and anti-PD-1 therapy compared to anti-PD-1 therapy alone, through a randomized phase II trial design.

Conditions

Microsatellite Instability High; Mismatch Repair Deficiency; Colorectal Cancer

Keywords

Solid tumor; Colorectal cancer; Unresectable or metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

RT and Anti-PD-1

In the pembrolizumab + RT arm, pembrolizumab will be started on study within 7 days (+/- 7 days) of start of RT.

Pembrolizumab will be given as standard of care in both arms

Group Type: ACTIVE_COMPARATOR

RT and Anti-PD-1

Intervention Type: COMBINATION_PRODUCT

limited metastatic site radiation

Anti-PD-1

anti-PD-1 therapy alone Pembrolizumab will be given as standard of care in both arms

Group Type: PLACEBO_COMPARATOR

Anti-PD-1

Intervention Type: DRUG

anti-PD-1 therapy alone

Interventions

RT and Anti-PD-1

limited metastatic site radiation

Intervention Type: COMBINATION_PRODUCT

Anti-PD-1

anti-PD-1 therapy alone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision to sign and date the consent form.

2. Stated willingness to comply with all study procedures and be available for the duration of the study.

3. Adult patients, 18-100 years of age.

4. ECOG 0 or 1.

5. Unresectable or metastatic MSI-H/dMMR tumors eligible to receive pembrolizumab according to FDA-approved indications:

• Solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options OR
• Colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan11

6. Confirmation from medical or gynecologic oncology that the patient is eligible to receive pembrolizumab per FDA-approved indication for patients not currently receiving pembrolizumab .

7. At least one site of disease amenable to radiation therapy per the acceptable dosing regimens outlined in section 6.2, and at least one additional site of measurable disease suitable for out-of-field response assessment.

8. Adequate baseline labs for initiation of trial treatment:

• absolute neutrophil count (ANC) >1,000/µL
• platelets >75,000/µL
• hemoglobin >8 g/dL
• serum creatinine < 1.5 x ULN
• serum total bilirubin < 1.5 x ULN
• AST and ALT < 2.5 x ULN, or < 5 x ULN if liver metastasis are present

Exclusion Criteria

1. Pregnant women. Pregnancy testing is required for all female subjects of childbearing potential.

2. Patients with active collagen vascular disease (CVD), specifically systemic lupus erythematosus or scleroderma. Patients with a history of CVD without evidence of active disease are eligible for enrollment at the discretion of the study PI.

3. History of immunodeficiency, hypersensitivity to pembrolizumab, or other medical contraindication to receipt of pembrolizumab.

4. Active infection.

5. Active CNS metastases. Patients with treated CNS metastases are eligible.

6. Patients with a separate non-cutaneous cancer diagnosis for which the patient has not been without evidence of disease for at least 5 years.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Cancer League of Colorado

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Colorado Hospital

Denver, Colorado, United States

Countries

United States

Other Identifiers

P30CA046934

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-0556.cc

Identifier Type: -

Identifier Source: org_study_id