Cancer Clinical Trial 
Eligibility Criteria:  
Available Therapy in 
Non-Curative Settings 
Guidance for Industry 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
  
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
 
July 2022 
Clinical/Medical   
Cancer Clinical Trial 
Eligibility Criteria:  
Available Therapy in 
Non-Curative Settings 
Guidance for Industry 
 
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Center for Drug Evaluation and Research 
Food and Drug Administration 
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https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
July 2022 
Clinical/Medical  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS .................................................................................................. 2 
 
  Contains Nonbinding Recommendations 
 
Cancer Clinical Trial Eligibility Criteria:  
Available Therapy in Non-Curative Settings 
Guidance for Industry1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the 
title page. 
 
 
 
 
I.  INTRODUCTION  
 
This guidance provides recommendations to clinical investigators and sponsors regarding the 
inclusion of patients who have not received available therapy2 (commonly referred to as existing 
treatment options) for their cancer in clinical trials of drugs3 and biological products for the 
treatment of cancer in the non-curative setting (i.e., when there is no potential for cure or 
prolonged/near normal survival). For the purpose of this guidance, non-curative is generally 
defined as 1) unresectable, locally advanced, or metastatic disease in solid tumors or 2) 
hematologic malignancies with unfavorable long-term overall survival.  
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract. This document is intended 
only to provide clarity to the public regarding existing requirements under the law. FDA 
guidance documents, including this guidance, should be viewed only as recommendations, unless 
specific regulatory or statutory requirements are cited. The use of the word should in Agency 
guidance means that something is suggested or recommended, but not required. 
 
 
 
 
 
1 This guidance has been prepared by the Oncology Center of Excellence (OCE), Center for Drug Evaluation and 
Research (CDER), and Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration.   
 
2 Refer to the guidance for industry Expedited Programs for Serious Conditions  Drugs and Biologics (May 2014) 
for a description of available therapy. We update guidances periodically. For the most recent version of a guidance, 
check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
3 For the purpose of this guidance, references to drugs include drugs approved under section 505 of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public 
Health Service Act (42 U.S.C. 262).   
 
  1  Contains Nonbinding Recommendations 
 
II.  BACKGROUND 
 
Under 21 CFR part 312, which applies to clinical investigations of drugs and biological products, 
FDA must determine that study subjects are not or would not be exposed to an unreasonable and 
significant risk of illness or injury (312.42(b)(1)(i) and (b)(2)(i)) to allow such trials to proceed. 
Therefore, in clinical trials evaluating investigational cancer drugs, eligibility criteria should 
generally include that patients should have received available therapy(ies) that offer the potential 
for cure in a substantial proportion of patients (e.g., available treatment for pediatric acute 
lymphoblastic leukemia, classic Hodgkin lymphoma, or testicular cancer). Alternatively, such 
available therapy should be administered to all patients in the trial, where the investigational 
drug is added to such therapy (i.e., add-on trial).  
 
Particularly in the early stages of oncology drug development, eligiblity criteria have historically 
included that patients should have received a certain number of available therapy(ies) or all 
available treatment options considered clinical standard of care. This type of requirement can 
inadvertently limit patient access to clinical trials and preclude patients from participating. In the 
non-curative setting, it is reasonable for patients to receive an investigational drug(s) in lieu of 
available therapy, as long as patients have been provided adequate information about all 
therapeutic options to make an informed decision on trial participation.  
 
 
III.  RECOMMENDATIONS     
 
When planning cancer clinical trials in the non-curative setting, sponsors should consider 
eligibility criteria as it pertains to available therapy(ies). FDA encourages sponsors to discuss 
their drug development plan with FDA early in development, including their approach to 
available therapy(ies) when developing eligibility criteria. In certain circumstances, FDA may 
request a specific approach for drug development. When designing cancer clinical trials, the 
following should be considered in the non-curative setting:  
 
  Patients may be eligible for inclusion in trials of investigational drugs, including first-in-
human trials, regardless of whether they have received available therapy in the non-
curative setting. Among other considerations, sponsors must ensure the elements of 
informed consent, as required by 21 CFR part 50.25, are addressed, including a 
disclosure of appropriate alternative procedures or courses of treatment, if any, that might 
be advantageous to the subject.4 The informed consent must clearly state that other 
treatment options known to confer clinical benefit exist, and must include discussion of 
reasonably foreseeable risks and any potential benefits associated with the investigational 
drug.5  
 
 
4 For additional information, see the guidance for industry Placebos and Blinding in Randomized Controlled Cancer 
Clinical Trials for Drug and Biological Products (August 2019). 
 
5 For additional information on informed consent, see 21 CFR part 50 and the draft guidance for IRBs, clinical 
investigators, and sponsors Informed Consent Information Sheet (July 2014). When final, this guidance will 
represent the FDAs current thinking on this topic. 
  2  Contains Nonbinding Recommendations 
 
  If interpretation of efficacy results requires a homogeneous patient population, evaluate 
patients who have received available therapy(ies) and patients who have not in separate 
cohorts. Alternatively, analyses of efficacy may be performed in pre-specified subgroup 
analyses, defined by prior receipt of available therapy(ies). 
 
  In early stage dose escalation studies, it may be reasonable to evaluate safety in all 
patients without stratifying for prior receipt of available therapy(ies), if the potential 
toxicities of the investigational oncology product are not expected to differ across these 
patient subgroups. 
  3