Notice2021-14194
Evaluating Cancer Drugs in Patients With Central Nervous System Metastases; Guidance for Industry; Availability
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Published
July 2, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance entitled "Evaluating Cancer Drugs in Patients with Central Nervous System Metastases; Guidance for Industry." The guidance document provides recommendations regarding the design of clinical trials of drugs and biological products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) that are intended to support product labeling describing the antitumor activity in patients with central nervous system (CNS) metastases from solid tumors originating outside the CNS. The guidance includes study design recommendations regarding the patient population, available therapy, prior therapies, assessment of CNS disease, study endpoints, and leptomeningeal disease. The guidance announced in this notice finalizes the draft guidance of the same title dated August 2020.
Full Text
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<title>Federal Register, Volume 86 Issue 125 (Friday, July 2, 2021)</title>
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[Federal Register Volume 86, Number 125 (Friday, July 2, 2021)]
[Notices]
[Pages 35305-35307]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-14194]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-0938]
Evaluating Cancer Drugs in Patients With Central Nervous System
Metastases; Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
[[Page 35306]]
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance entitled ``Evaluating Cancer Drugs
in Patients with Central Nervous System Metastases; Guidance for
Industry.'' The guidance document provides recommendations regarding
the design of clinical trials of drugs and biological products
regulated by the Center for Drug Evaluation and Research (CDER) and the
Center for Biologics Evaluation and Research (CBER) that are intended
to support product labeling describing the antitumor activity in
patients with central nervous system (CNS) metastases from solid tumors
originating outside the CNS. The guidance includes study design
recommendations regarding the patient population, available therapy,
prior therapies, assessment of CNS disease, study endpoints, and
leptomeningeal disease. The guidance announced in this notice finalizes
the draft guidance of the same title dated August 2020.
DATES: The announcement of the guidance is published in the Federal
Register on July 2, 2021.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2020-D-0938 for ``Evaluating Cancer Drugs in Patients with Central
Nervous System Metastases.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of the guidance to the
Office of Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist the office in processing
your requests. The guidance may also be obtained by mail by calling
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Shanthi Marur, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 2369, Silver Spring, MD 20993-0002, 240-
402-6373; or Stephen Ripley, Center for Biologics Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a document entitled
``Evaluating Cancer Drugs in Patients with Central Nervous System
Metastases.'' This guidance provides recommendations for sponsors
designing clinical trials of drugs and biological products regulated by
CDER and CBER that are intended to support product labeling describing
the antitumor activity in patients with CNS metastases from solid
tumors originating outside the CNS. Specifically, the guidance includes
recommendations regarding the patient population, available therapy,
prior therapies, assessment of CNS disease, study endpoints, and
leptomeningeal disease. The guidance describes that CNS metastases
should be evaluated in the context of the entire disease burden and
discusses how treatment effects may be described in drug labeling. The
recommendations pertain to clinical trials for systemic anticancer
drugs where patients with CNS metastases are included in the study
population. These recommendations are also applicable to
[[Page 35307]]
trials conducted exclusively in patients with CNS metastases.
CNS metastases are associated with significant morbidity and
mortality and development of therapeutic products for patients with CNS
metastases is needed. FDA has participated in efforts to facilitate
drug development for patients with CNS metastases, including a March
2019 ``Workshop on Product Development for CNS Metastases.''
Stakeholders at this meeting stated there is a need for further FDA
guidance on specific topics, including identifying optimal study
endpoints. Study design challenges for CNS metastases include
uncertainty regarding optimal endpoints, lack of standardized response
assessments, understanding how CNS metastases are evaluated in the
context of the entire burden of metastatic disease to characterize a
drug's potential benefit (e.g., timing of CNS radiographic assessments
relative to other sites of metastases), and interpreting radiographic
response in the setting of recent radiation therapy or surgery. This
guidance is intended to provide recommendations on these study design
challenges.
In the Federal Register of August 27, 2020 (85 FR 53007), FDA
announced the availability of the draft guidance ``Evaluating Cancer
Drugs in Patients with Central Nervous System Metastases'' dated August
2020. FDA received several comments on the draft guidance and those
comments were considered as the guidance was finalized. A summary of
changes includes: Clarification on the number of stratification factors
the protocol should specify in order to minimize bias, confirmation of
the version of Response Evaluation Criteria in Solid Tumours (RECIST)
that should be referred to when evaluating CNS disease, clarification
that both CNS and systematic duration of response should be captured
and the addition of a 6-month timepoint, and the addition of
progression-free survival in patients with brain metastasis as another
measurement to be reported when CNS is a common metastatic site. In
addition, editorial changes were made to improve clarity. The guidance
announced in this notice finalizes the draft guidance dated August 27,
2020.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Evaluating Cancer Drugs in Patients with
Central Nervous System Metastases.'' 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.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 312 have been approved under OMB control
number 0910-0014; the collections of information in 21 CFR part 314
have been approved under OMB control number 0910-0001; the collections
of information in 21 CFR part 601 have been approved under 0910-0338;
and the collections of information in 21 CFR 201.56 and 201.57 have
been approved under OMB control number 0910-0572.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
either <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a> or
<a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: June 28, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-14194 Filed 7-1-21; 8:45 am]
BILLING CODE 4164-01-P
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