Description
This guidance provides recommendations to sponsors of drugs or biologics for the treatment of cancer regarding the design and conduct of clinical trials intended to simultaneously evaluate more than one investigational drug and/or more than one cancer type within the same overall trial structure (master protocols) in adult and pediatric cancers. In general, the recommended phase 2 dose (RP2D) should have been established for an investigational drug or drugs evaluated in a master protocol.
Scope & Applicability
Product Classes
3The narrow therapeutic margin of safety for many oncology drugs for use in animals presents unique HUS considerations
IVD device clinical studies conducted on de-identified specimens
Products for which batch/lot information is particularly important
Stakeholders
8Entity responsible for submitting applications under section 524B
Role involved in changing amendment classification; The regulatory project manager will issue the applicant an acknowledgment letter
Institutional Review Board providing study approvals
FDA recommends the use of a central IRB to facilitate review of master protocols.
Should have training and experience in cancer research and clinical trials.
Body that may propose protocol amendments or maintain trial integrity
Governs top dose in clinical studies
Responsible for submission and communication oversight; Safeguard the rights, safety and well-being of trial participants; Reviewing trial conduct and records
Regulatory Context
Attributes
1Risk classification for medical device clinical investigations.; A classification for medical device studies.; A risk determination for a clinical study.
Identified Hazards
Hazards
2requires rapid communication to investigators and FDA
An immediate hazard that may require closure of a substudy.
Related CFR Sections (13)
- 21CFR312.30§ 312.30 Protocol amendments.
Once an IND is in effect, a sponsor shall amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application. This section sets forth the provisions under which new protocols may be submitted and changes in previously submitted protocols maRead full regulation →
- 21CFR56.104§ 56.104 Exemptions from IRB requirement.
The following categories of clinical investigations are exempt from the requirements of this part for IRB review:Read full regulation →
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR50.20§ 50.20 General requirements for informed consent.
Except as provided in §§ 50.22 , 50.23 , and 50.24 , no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An invesRead full regulation →
- 21CFR312.66§ 312.66 Assurance of IRB review.
An investigator shall assure that an IRB that complies with the requirements set forth in part 56 will be responsible for the initial and continuing review and approval of the proposed clinical study. The investigator shall also assure that he or she will promptly report to the IRB all changes in thRead full regulation →
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 21CFR50.52§ 50.52 Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects.
Any clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter in which more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is likely tRead full regulation →
- 21CFR312.42§ 312.42 Clinical holds and requests for modification.
(a) General. A clinical hold is an order issued by FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. The clinical hold order may apply to one or more of the investigations covered by an IND. When a proposed study is placed on clinical hold, subjectRead full regulation →
- 21CFR812.3§ 812.3 Definitions.
(a) Act means the Federal Food, Drug, and Cosmetic Act (sections 201-901, 52 Stat. 1040 et seq., as amended ( 21 U.S.C. 301-392 )).Read full regulation →
- 21CFR812.2§ 812.2 Applicability.
(a) General. This part applies to all clinical investigations of devices to determine safety and effectiveness, except as provided in paragraph (c) of this section.Read full regulation →
- 21CFR56.103§ 56.103 Circumstances in which IRB review is required.
(a) Except as provided in §§ 56.104 and 56.105 , any clinical investigation which must meet the requirements for prior submission (as required in parts 312, 812, and 813) to the Food and Drug Administration shall not be initiated unless that investigation has been reviewed and approved by, and remaiRead full regulation →
- 21CFR812.20§ 812.20 Application.
(a) Submission.Read full regulation →
- 21CFR312.50§ 312.50 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators, providing them with the information they need to conduct an investigation properly, ensuring proper monitoring of the investigation(s), ensuring that the investigation(s) is conducted in accordance with the general investigational plan Read full regulation →
Related Warning Letters (10)
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, M.D.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-06-03
Bioresearch Monitoring Program
Amy Lightner, MD
- 2025-03-25
Clinical Investigator
Americo F. Padilla, M.D.
- 2024-11-05
Institutional Review Board (IRB)
Armstrong County Memorial Hospital
- 2024-10-22
Clinical Investigator
Namita A. Goyal, M.D.
- 2024-10-08
Institutional Review Board (IRB)
Louisiana State University Health Science Center IRB
- 2024-07-16
Bioresearch Monitoring Program/IRB
Massachusetts Institute of Technology MIT
- 2024-06-18
Clinical Investigator (Sponsor)
Angela D. Ritter, M.D.
- 2024-03-26
Institutional Review Board (IRB)
New York State Psychiatric Institute IRB
See Also (8)
- Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices (Status: Draft)
- Emergency Use of an Investigational Drug or Biologic: Guidance for Institutional Review Boards and Clinical Investigators (Status: Final)
- CHAPTER 48 - 7348.809 Bioresearch Monitoring (Status: Final)
- Expanded Access to Investigational Drugs for Treatment Use - Questions and Answers: Guidance for Industry (Status: Final)
- Waiver of IRB Requirements for Drug and Biological Product Studies: Guidance For Sponsors, Clinical Investigators, and IRBs (Status: Final)
- Institutional Review Board (IRB) Review of Individual Patient Expanded Access Submissions for Investigational Drugs and Biological Products: Guidance for IRBs and Clinical Investigators (Status: Final)
- Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies (Status: Final)
- Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers (Status: Final)