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

NCT04001101 | Withdrawn Phase 2 DMC

• 2 other identifiers: 19-0556.ccP30CA046934
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Microsatellite Instability High; Mismatch Repair Deficiency; Colorectal Cancer

Keywords

Solid tumor; Colorectal cancer; Unresectable or metastatic

Outcome Measures

Primary Outcomes (1)

• Out-of-field ORR improvement

  • Out-of-field objective response rate (ORR: CR+PR) according to RECIST 1.1 assessment

  12 months

Secondary Outcomes (6)

• in-field tumor control and disease control

  12 Months

• Determine the chronology and profile of the radiation-associated immune response.

  12 months

• Durability of disease response

  12 months

• Progression-free Survival

  12 months

• Overall Survival

  12 Months

Study Arms (2)

RT and Anti-PD-1

ACTIVE COMPARATOR

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

Combination Product: RT and Anti-PD-1

Anti-PD-1

PLACEBO COMPARATOR

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

Drug: Anti-PD-1

Interventions

RT and Anti-PD-1 COMBINATION_PRODUCT

limited metastatic site radiation

RT and Anti-PD-1

Anti-PD-1 DRUG

anti-PD-1 therapy alone

Anti-PD-1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Adult patients, 18-100 years of age.
• ECOG 0 or 1.
• 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
• Confirmation from medical or gynecologic oncology that the patient is eligible to receive pembrolizumab per FDA-approved indication for patients not currently receiving pembrolizumab .
• 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.
• 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

You may not qualify if:

• Pregnant women. Pregnancy testing is required for all female subjects of childbearing potential.
• 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.
• History of immunodeficiency, hypersensitivity to pembrolizumab, or other medical contraindication to receipt of pembrolizumab.
• Active infection.
• Active CNS metastases. Patients with treated CNS metastases are eligible.
• Patients with a separate non-cutaneous cancer diagnosis for which the patient has not been without evidence of disease for at least 5 years.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Cancer Institute (NCI): collaborator
• Cancer League of Colorado: collaborator

Study Sites (1)

University of Colorado Hospital

Denver, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Turcot syndrome; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In an effort to minimize bias, the study will utilize a randomization. The randomization list will be generated by the study biostatistician and provided only to the study personnel who will be responsible for assigning each subject to a cohort of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2019
• First Posted: June 27, 2019
• Study Start: October 10, 2019
• Primary Completion: November 17, 2021
• Study Completion: November 17, 2021
• Last Updated: November 30, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)